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Background/objective: Primary hyperparathyroidism is the most common cause of hypercalcemia. Hypercalcemia secondary to giant parathyroid adenomas and parathyroid carcinomas share substantial clinical similarities and their differentiation is challenging. Case report: We present the case of a 72-year-old female with profound lethargy and confusion associated with polydipsia and polyuria, who was found to have an extremely elevated serum calcium level of 18.3 mg/dL (normal 8.4–10.5 mg/dL), ionized calcium 2.56 mmol/L (normal 1.20–1.32 mmol/L) and intact parathyroid hormone of 1838 pg/mL (normal 15–65 pg/mL). Ultrasound revealed a large hypoechoic nodule measuring 2.5 x 1.8 × 2.0 cm located in the right thyroid bed. Computed tomography revealed a hypoattenuating mass in the same region without obvious soft tissue invasion or lymphadenopathy. Technetium-99 m sestamibi with single-photon emission computed tomography identified intense focal radiotracer uptake at the same location most consistent with hyperfunctional parathyroid tissue. Patient underwent surgical exploration and resection of a parathyroid mass, which weighed 12.1 g and measured 4.6 x 2.5 × 1.8 cm. Pathology confirmed a diagnosis of benign parathyroid adenoma. Patient's laboratory values normalized and her mental status improved significantly, and she was discharged in stable condition. Discussion: This is a rare case of a symptomatic patient with extreme primary hyperparathyroidism and hypercalcemia that was found to have a benign giant parathyroid adenoma, rather than carcinoma. Conclusion: Differentiation between large hyperfunctioning parathyroid adenoma and parathyroid carcinoma is nontrivial due to shared characteristics of each. Therefore, the final diagnosis requires imaging and histopathological examination.

Introduction: To combine numerical simulations, in vitro and in vivo experiments to evaluate the feasibility of measuring diffusion exchange across the cell membrane with diffusion exchange spectroscopy (DEXSY)., Methods: DEXSY acquisitions were simulated over a range of permeabilities in nerve tissue and yeast substrates. In vitro measurements were performed in a yeast substrate and in vivo measurements in mouse tumor xenograft models, all at 9.4 T., Results: Diffusion exchange was observed in simulations over a physiologically relevant range of cell permeability values. In vitro and in vivo measures also provided evidence of diffusion exchange, which was quantified with the Diffusion Exchange Index (DEI)., Conclusions: Our findings provide preliminary evidence that DEXSY can be used to make in vivo measurements of diffusion exchange and cell membrane permeability., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Cancer cells differ in size from those of their host tissue and are known to change in size during the processes of cell death. A noninvasive method for monitoring cell size would be highly advantageous as a potential biomarker of malignancy and early therapeutic response. This need is particularly acute in brain tumours where biopsy is a highly invasive procedure. Here, diffusion MRI data were acquired in a GL261 glioma mouse model before and during treatment with Temozolomide. The biophysical model VERDICT (Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours) was applied to the MRI data to quantify multi-compartmental parameters connected to the underlying tissue microstructure, which could potentially be useful clinical biomarkers. These parameters were compared to ADC and kurtosis diffusion models, and, measures from histology and optical projection tomography. MRI data was also acquired in patients to assess the feasibility of applying VERDICT in a range of different glioma subtypes. In the GL261 gliomas, cellular changes were detected according to the VERDICT model in advance of gross tumour volume changes as well as ADC and kurtosis models. VERDICT parameters in glioblastoma patients were most consistent with the GL261 mouse model, whilst displaying additional regions of localised tissue heterogeneity. The present VERDICT model was less appropriate for modelling more diffuse astrocytomas and oligodendrogliomas, but could be tuned to improve the representation of these tumour types. Biophysical modelling of the diffusion MRI signal permits monitoring of brain tumours without invasive intervention. VERDICT responds to microstructural changes induced by chemotherapy, is feasible within clinical scan times and could provide useful biomarkers of treatment response.

We present a high-resolution mass spectrometric (MS) footprinting method enabling identification of contact amino acids in protein-protein complexes. The method is based on comparing surface topologies of a free protein versus its complex with the binding partner using differential accessibility of small chemical group selective modifying reagents. Subsequent MS analysis reveals the individual amino acids selectively shielded from modification in the protein-protein complex. The current report focuses on probing interactions between full-length HIV-1 integrase and its principal cellular partner lens epithelium-derived growth factor. This method has a generic application and is particularly attractive for studying large protein-protein interactions that are less amenable for crystallographic or NMR analysis.