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GNE Myopathy is a unique recessive neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness, caused by mutations in the GNE gene, which is a key enzyme in the biosynthesis of sialic acid. To date, the precise pathophysiology of the disease is not well understood, and no reliable animal model is available. Gne KO is embryonically lethal in mice. To gain insights into GNE function in muscle, we have generated an inducible muscle Gne KO mouse. To minimize the contribution of the liver to the availability of sialic acid to muscle via the serum, we have also induced combined Gne KO in liver and muscle. A mouse carrying loxp sequences flanking Gne exon3 was generated by Crispr/Cas9 and bred with a human skeletal actin (HAS) promoter driven CreERT mouse. Gne muscle knock out was induced by tamoxifen injection of the resulting homozygote GneloxpEx3loxp/HAS Cre mouse. Liver Gne KO was induced by systemic injection of AAV8 vectors carrying the Cre gene driven by the hepatic specific promoter of the thyroxine binding globulin gene. Characterization of these mice for a 12-month period showed no significant changes in their general behaviour, motor performance, muscle mass and structure in spite of a dramatic reduction in sialic acid content in both muscle and liver. We conclude that post weaning lack of Gne and sialic acid in muscle and liver have no pathologic effect in adult mice. These findings could reflect a strong interspecies versatility, but also raise questions about the loss of function hypothesis in Gne Myopathy. If these findings apply to humans they may have a major impact on therapeutic strategies. [ABSTRACT FROM AUTHOR]

It is generally believed that multinodular goiter (MNG) is associated with a lower risk of malignancy compared to solitary thyroid nodules (STN). This will be the null hypothesis in this retrospective study and we aim to prove or reject it. Medical files and histopathology reports of 600 patients who underwent thyroidectomy over 4-year period were reviewed. Data including patient' age, gender, presentation, ultrasonography, FNAC, surgical procedures, final histopathologic diagnosis and stage of malignant tumors were collected and analyzed. The primary end point was assessment of risk of thyroid carcinoma in patients with MNG compared to those with STN. Secondary endpoints included demographic differences and prognosis. There were 459 females (76.5%). Mean age was 44.3 ± 14.5 years (range 14–85). After exclusion of 33 patients, 224 (39.5%) had STN and 343 (60.5%) had MNG. The prevalence of thyroid cancer was 41.1% (92/224) in STN compared to 29.2% (100/343) in MNG (Chi-Square = 8.593, p < 0.01). However, on multiple logistic regression analysis this correlation was found insignificant (p = 0.640). Only male gender (p = <0.000005) and preoperative impression of malignancy (p = 0.000082) were significantly associated with thyroid carcinoma. The risk of thyroid carcinoma in STN and MNG was similar. Male gender was identified as a risk factor for thyroid cancer while age, number and size of nodules were not. [ABSTRACT FROM AUTHOR]