A genetically-encoded fluorescence-based reporter to spatiotemporally investigate mannose-6-phosphate pathway.

Maintenance of a pool of active lysosomes with acidic pH and degradative hydrolases is crucial for cell health. Abnormalities in lysosomal function are closely linked to diseases, such as lysosomal storage disorders, neurodegeneration, intracellular infections, and cancer among others. Emerging body of research suggests the malfunction of lysosomal hydrolase trafficking pathway to be a common denominator of several disease pathologies. However, available conventional tools to assess lysosomal hydrolase trafficking are insufficient and fail to provide a comprehensive picture about the trafficking flux and location of lysosomal hydrolases. To address some of the shortcomings, we designed a genetically-encoded fluorescent reporter containing a lysosomal hydrolase tandemly tagged with pH sensitive and insensitive fluorescent proteins, which can spatiotemporally trace the trafficking of lysosomal hydrolases. As a proof of principle, we demonstrate that the reporter can detect perturbations in hydrolase trafficking, that are induced by pharmacological manipulations and pathophysiological conditions like intracellular protein aggregates. This reporter can effectively serve as a probe for mapping the mechanistic intricacies of hydrolase trafficking pathway in health and disease and is a utilitarian tool to identify genetic and pharmacological modulators of this pathway, with potential therapeutic implications.

Dosing of radioactive iodine in end-stage renal disease patient with thyroid cancer.

We describe detailed administration of thyroidal and extrathyroidal doses of radioiodine to a patient with end-stage renal disease on hemodialysis. A thorough description of area under curve measurements in a patient with compromised renal function has rarely been described in the literature. Few publications have described thyroid cancer management of patients on hemodialysis, and we believe our management will aid in patient treatment in the future. LEARNING POINTS: Scheduling of hemodialysis is important when administering radioactive iodine.Treatment of thyroid cancer with radioiodine in patients with end-stage renal disease requires multidisciplinary approach coordinating dialysis, nuclear medicine and endocrinologists care.Balancing ideal dosage of I131 and the timing of dialysis to insure maximal thyroidal uptake and minimal extra thyroidal I131 concentration is necessary.

Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment.

Subclinical hyperthyroidism (SHy), the mildest form of hyperthyroidism, is diagnosed in patients having a persistently low or undetectable serum concentration of thyroid-stimulating hormone (TSH) with normal free T4 and T3 concentrations. Although overt hyperthyroidism is associated with an increased risk of adverse cardiovascular outcomes, the cardiovascular risk of SHy is controversial. Multiple studies have demonstrated an increased risk of atrial fibrillation, especially in older individuals with TSH levels <0.1 mU/L. The effects of SHy on all-cause and cardiovascular mortality are not clear, but recent meta-analyses suggest a modest increase in mortality, with the risk increasing with age and associated with the lowest TSH levels. The long-term consequences of SHy in young- and middle-aged adults, and in those with TSH levels are mildly low, are uncertain. For these reasons, guidelines for treatment are based on patient age, the degree of TSH suppression, symptoms consistent with hyperthyroidism, and overall cardiovascular and osteoporotic fracture risks.