We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes. A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycaemic controls. miRNAs were identified using microarray profiling and literature review and validated by quantitative PCR (qPCR). In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, miR-452-5p, miR-126-3p, miR-130b-3p, miR-148a-3p, miR-let-7a-5p and miR-let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase α1 (AMPKα1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKα1 expression was also decreased in placental tissues of IGDM. The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycaemia was very well controlled by current standards. Decreased expression of AMPKα1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at 1 month of age and, if persistent, may predispose offspring to future metabolic disease.
Chronic hyponatremia is very rare in children and is often seen in the setting of congestive heart failure or liver failure in adults. Here, we report an 8-year-old child with hypothalamic glioma who presented with severe hyponatremia. Initial management consisted of fluid restriction. This was very difficult for the child to follow and the child developed bizarre drinking habits requiring intervention from child psychiatry. So therapy was initiated with low dose V2 receptor antagonist under close inpatient monitoring. While initial response was reassuring, her sodium levels tended to drift down with longer duration of treatment requiring us to increase the dose frequently. Her response to therapy and her stable clinical situation off therapy suggest that she may have reset osmostat.
Heterotopic Ossification (HO) is formation of normal bone in extraskeletal tissues, such as skin, subcutaneous tissue and deep connective tissue. Heterotopic ossification can be hereditary or nonhereditary in nature. We report two cases of rare hereditary forms of heterotopic ossification namely Fibrodysplasia Ossificans Progressiva (FOP) and Progressive Osseous Heteroplasia (POH). Hereditary forms of heterotopic ossification are progressive and severely debilitating in nature. Though these disorders are rare, awareness and knowledge about these disorders will help in early identification of such unique cases, leading to appropriate referral and management.
Case Presentations Case 1A 4 year old Caucasian female was admitted with history of painful soft tissue swelling and induration on her right upper back, posterior neck and torso following an all-terrain vehicle accident that occurred a few weeks before her admission. Patient also reported trouble sitting up and increasing stiffness with ambulation. She had been evaluated in orthopedic clinic a few months previously for scoliosis and suspected Klippel-Feil anomaly. Physical examination revealed extensive tender indurated swellings over upper back and neck. She was also noted to have bilateral hallux valgus (Figure 1). Laboratory data revealed normal electrolytes, blood cell counts, liver enzymes, alkaline phosphatase and LDH levels. CT of her shoulder revealed a bony extension of the left anterior/inferior clavicle ( Figure 1) and was reported as exostosis of the clavicle with nonspecific soft tissue stranding through the lower neck and chest wall musculature, findings inconsistent with KlippelFeil syndrome. Genetic testing for FOP was done because of a strong clinical suspicion and due to the presence of hallux valgus, which revealed a c.617G>A transition in ACVR1 gene, resulting in a missense mutation (p.R206H), commonly associated with FOP [1].
Case 2A 17 year old Caucasian male presented to our endocrinology/bone clinic for evaluation of subcutaneous nodules. The lesions were first noted on his right index finger at two years of age. Over time similar lesions were noted on his right extremity. In the previous year he had noted more lesions in his right hand with extension into the forearm. He also had complaints of mild right wrist joint pain and stiffness with activity. He had undergone surgical removal of the lesions repeatedly (seven times). Family history was negative for ectopic ossifications, rickets, hormone deficiencies or other bone disorders. There was no history of consanguinity.Physical examination showed a well appearing Tanner V adolescent, with no features of Albright Hereditary Osteodystrophy (AHO). Extremity examination was remarkable for 2-4 mm sized bony lesions palpable in the inter-digital space of right index and middle finger and also extending along the radial aspect of the forearm. He was noted to have decreased mobility of the index and middle fingers. Similar lesions were noted on the dorsal aspect of the second digit ...
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