Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia.

BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury. METHODS: To visualize effects of neuroinflammation on neurogenesis/gliogenesis, we created a transgenic model bearing the dual reporter system luciferase and GFP under transcriptional control of the murine nestin promoter. In this model, transcriptional activation of nestin was visualized from the brains of living animals using biophotonic/bioluminescence molecular imaging and a high resolution charged coupled device camera. Nestin induction profiles in vivo and in tissue sections were analyzed in two different experimental paradigms: middle cerebral artery occlusion and lipopolysaccharide-induced innate immune stimuli. RESULTS: We report here a context- and injury-dependent induction and cellular expression profile of nestin. While in the baseline conditions the nestin signal and/or GFP expression was restricted to neuronal progenitors, the cellular expression patterns of nestin following innate immune challenge and after stroke markedly differed shifting the cellular expression patterns towards activated microglia/macrophages and astrocytes. CONCLUSIONS: Our results suggest that nestin may serve as a context-dependent biomarker of inflammatory response in glial cells including activated microglia/macrophages.

A case of unilateral post-COVID-19 adrenal haemorrhage and follow-up during pregnancies.

Summary: The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion. Learning points: Unilateral adrenal haemorrhage can occur as a complication of COVID-19 and should be considered in the differential diagnosis of heterogeneous adrenal masses if there is a history of recent infection. Management of large indeterminate adrenal masses during pregnancy poses several challenges and should be led by an experienced multidisciplinary team. Underlying adrenal tumours may trigger non-traumatic haemorrhages, especially if exacerbated by stressful illness.

Therapeutic Challenges in the Management of Acute Pulmonary Embolism in a Cancer Patient with Chemotherapy-induced Thrombocytopenia.

This case demonstrates the therapeutic challenges encountered when managing an acute pulmonary embolism in a cancer patient with thrombocytopenia. A 64-year-old man with a history of lung cancer receiving chemotherapy was admitted to Walsall Manor Hospital with haemodynamic instability consistent with a pulmonary embolism, proven on computed tomographic pulmonary angiogram. His platelet count was noted to be 35×109/l (chemotherapy-induced thrombocytopenia). After discussions, he was deemed not suitable for thrombolysis based on risk versus benefits. The patient was initially transfused one adult dose of platelets and treated with half the therapeutic dose of low molecular weight heparin (LMWH). The same management plan was followed until the platelet count exceeded 50×109/l, after which the patient was established on the full therapeutic dose of LMWH. Clinically, the patient improved and was discharged. Three months after discharge, follow-up revealed sustained clinical improvement while the patient continued to be on the full therapeutic dose of LMWH with a stable platelet count. LEARNING POINTS: Cancer patients have a three-fold higher risk of venous thromboembolism compared with non-cancer patients, but also a higher risk of bleeding, hence neoplasm is considered an absolute contraindication to thrombolysis by the European Society of Cardiologists.The management of an acute pulmonary embolism in cancer patients with thrombocytopenia is still debated. However, a few recognised medical societies and expert opinions have established recommendations on this specific area, such as the British Committee for Standards in Haematology, the American Society of Clinical Oncology and the International Society of Thrombosis and Haemostasis.Expert opinion agrees on: giving the full therapeutic dose of low molecular weight heparin (LMWH) if the platelet count is above 50×109/l; if it drops below 50×109/l, halving the dose of LMWH with or without platelet transfusion until the platelet count improves above 50×109/l; and when the platelet count is below 20-30×109/l, withholding anticoagulation and considering the insertion of an inferior vena cava filter.

Post-radioiodine De Novo Onset Graves' Ophthalmopathy: Case Reports and a Review of the Literature.

New-onset Graves' ophthalmopathy (GO) following radioiodine treatment (RAI) and worsening of existing GO are well-described in the endocrinology literature. These phenomena are recognized by ophthalmologists, yet poorly documented in the ophthalmology literature. Two male patients, aged 43 and 62 years, respectively, with Graves' disease without GO, received RAI. Four months later, one patient developed acute GO with unilateral reduction in visual acuity, conjunctival chemosis, lagophthalmos, bilateral severely restricted ocular motility, and lid retraction. High-dose intravenous steroids, followed by oral steroids, led to a dramatic clinical improvement. The second patient received a second dose of RAI for persistent hyperthyroidism and subsequently developed acute GO-comprising restricted ocular motility, peri-orbital swelling, and conjunctival chemosis. Symptoms gradually resolved on continued carbimazole treatment. Neither patient received pre-RAI prophylactic glucocorticoids, as currently they are only recommended for patients with pre-existing GO or multiple risk factors. We discuss the limitations of using this risk-based approach in preventing new-onset GO following RAI therapy.

Assessing nociceptive sensitivity in mouse models of inflammatory and neuropathic trigeminal pain.

Chronic orofacial pain encompasses a range of debilitating conditions, however in contrast to other body regions, few animal models are available to investigate mechanisms and treatments in the trigeminal area. Particularly, there is a lack of reliable models and testing methods in mice. We have behaviourally tested C57BL/6 mice subjected to unilateral chronic constriction injury (CCI) of the infraorbital nerve (IoN) or unilateral injections of Complete Freunds Adjuvant (CFA) into the vibrissal pad region with the aid of von Frey filaments and air-puffs and the use of a newly designed restraining device. These models were validated by suppressing the pain responses with appropriate drugs. The IoN-CCI group showed significant hyperalgesia on the ipsilateral side in comparison to baseline values for up to 20 days post-CCI following von Frey and air-puff stimulation. Gabapentin (60mg/kg), but not saline, temporarily reversed the hyperalgesia. Animals that received a CFA injection showed hyperresponsivity to both von Frey and air-puff stimulation for up to 4 days post injection. These effects were transiently reversed with 3mg/kg i.p. morphine but not saline. Our study proposes a new restraining device for mice, and validates a behavioural testing procedure of several facial pain models in mice, allowing for reproducible and robust assessment of the effects of pain-related agents and treatments, or phenotyping of genetically modified animals.