Bacteriomimetic poly-γ-glutamic acid surface coating for hemocompatibility and safety of nanomaterials

Poly-γ-glutamic acid (PGA), a major component of the bacterial capsule, is known to confer hydrophilicity to bacterial surfaces and protect bacteria from interactions with blood cells. We tested whether applying a bacteriomimetic surface coating of PGA modulates interactions of nanomaterials with blood cells or affects their safety and photothermal antitumor efficacy. Amphiphilic PGA (APGA), prepared by grafting phenylalanine residues to PGA, was used to anchor PGA to reduced graphene oxide (rGO) nanosheets, a model of hydrophobic nanomaterials. Surface coating of rGO with bacterial capsule-like APGA yielded APGA-tethered rGO nanosheets (ArGO). ArGO nanosheets remained stable in serum over 4?weeks, whereas rGO in plain form precipitated in serum within 5?minutes. Moreover, ArGO did not interact with blood cells, whereas rGO in plain form or as a physical mixture with PGA formed aggregates with blood cells. Mice administered ArGO at a dose of 50?mg/kg showed 100% survival and no hepatic or renal toxicity. No mice survived exposure at the same dose of rGO or a PGA/rGO mixture. Following intravenous administration, ArGO showed a greater distribution to tumors and prolonged tumor retention compared with other nanosheet formulations. Irradiation with near-infrared light completely ablated tumors in mice treated with ArGO. Our results indicate that a bacteriomimetic surface modification of nanomaterials with bacterial capsule-like APGA improves the stability in blood, biocompatibility, tumor distribution, and photothermal antitumor efficacy of rGO. Although APGA was used here to coat the surfaces of rGO, it could be applicable to coat surfaces of other hydrophobic nanomaterials.     

Disruption of Dhcr7 and Insig1/2 in cholesterol metabolism causes defects in bone formation and homeostasis through primary cilium formation

Human linkage studies suggest that craniofacial deformities result from either genetic mutations related to cholesterol metabolism or high-cholesterol maternal diets. However, little is known about the precise roles of intracellular cholesterol metabolism in the development of craniofacial bones, the majority of which are formed through intramembranous ossification. Here, we show that an altered cholesterol metabolic status results in abnormal osteogenesis through dysregulation of primary cilium formation during bone formation. We found that cholesterol metabolic aberrations, induced through disruption of either Dhcr7(which encodes an enzyme involved in cholesterol synthesis) or Insig1 and Insig2(which provide a negative feedback mechanism for cholesterol biosynthesis), result in osteoblast differentiation abnormalities. Notably, the primary cilia responsible for sensing extracellular cues were altered in number and length through dysregulated ciliary vesicle fusion in Dhcr7 and Insig1/2 mutant osteoblasts. As a consequence, WNT/β-catenin and hedgehog signaling activities were altered through dysregulated primary cilium formation.Strikingly, the normalization of defective cholesterol metabolism by simvastatin, a drug used in the treatment of cholesterol metabolic aberrations, rescued the abnormalities in both ciliogenesis and osteogenesis in vitro and in vivo. Thus, our results indicate that proper intracellular cholesterol status is crucial for primary cilium formation during skull formation and homeostasis.     

The diagnosis and management of temporal arteritis

Temporal arteritis (TA), or giant cell arteritis, is a systemic autoimmune vasculitis affecting patients over 50 years of age. It can cause rapid, irreversible bilateral vision loss in older adults and is therefore considered an ophthalmological emergency. Many of the symptoms and signs of TA can be vague, non-specific and gradual in onset, often leading to a delayed or inaccurate diagnosis. As such, it is important for a wide variety of primary optometrists and health practitioners to maintain a robust understanding of the clinical presentation, key investigations and time-sensitive management of this disease, as early initiation of treatment for TA can be vision- and life-saving.     

Twist technique for removal of spinal extradural arachnoid cyst: technical note

Study design

We document a spinal extradual arachnoid cyst treated by twist technique. The cyst is tightly adherent to the neural tissue or the dura, and the communication stalk is little or short.

Objective

To demonstrate the effectiveness of twist technique of closure of the communication stalk for the removal of spinal extradural arachnoid cyst.

Summary of background data

The standard treatment for a spinal extradural arachnoid cyst is complete excision of the cyst, followed by obliteration of the communication stalk and repair of the dural defect. To our knowledge, twist technique of the communication stalk for removal of spinal extradural arachnoid cyst has not been reported.

Methods

A 44-year-old woman presented with a 10-year history of pain and dysesthesia, initially in the posterior neck region and extending gradually to the distal portion of the right upper extremity. Pain and dysesthesia were exaggerated when she was lying down and relieved when standing or walking. She was diagnosed with an extradural arachnid cyst ranging from spinal regions T1 to T3 using MRI. Computerized tomography myelography revealed a mass located posterior to the spinal cord. Pooling of contrast medium was observed in the lesion indicating communication with the subarachnoid space. Laminectomy of the T1–T3 region was performed, preserving the spinous processes and the facet joints. A short communication stalk was found at the proximal root sleeve of right T3. This stalk was closed using twist technique.

Results

The patient experienced marked reduction of pain and dysesthesia after surgery, and the headache and blurred vision completely disappeared. Five days after the operation, she was discharged home in good condition. Postoperative 1 year later, the patient had completely recovered and resumed her normal life.

Conclusions

Twist technique can be seen safe and effective as another surgical option for spinal extradural arachnoid cysts containing a short stalk and dense fibrous adhesion with the dura mater.     

Comparison of ICC patients with hepatitis B infection to those with no major risk factors for HCC

BackgroundThere has been renewed interest in HBV-associated ICC, because it could share a common carcinogenesis disease process with HCC. We investigated whether there is a difference in clinical outcome between ICC patients with HBV infection and those without any major risk factors for HCC.MethodsA total of 253 curatively resected, surgically diagnosed ICC patients were analyzed and divided into two groups according to the presence or absence of major risk factors for HCC: an HBV group (n = 45) and a non–HCC–risk (NHR) group (n = 208).ResultsLymph node metastasis was more frequently observed in the NHR group (HBV vs. NHR: 8.89% vs. 24.52%, P = 0.027). Patients in the HBV group demonstrated more favorable survival than those in the NHR group. However, this difference was not statistically significant (5-year survival rate, 54.7% vs. 42.3%, P = 0.128). Cumulative recurrence rate in the HBV group was 62.2%, which was not significantly different from 63.0% in the NHR group (P = 1.000).ConclusionThis study found that while ICC patients with HBV infection showed some favorable tumor characteristics, patients' stage-specific survival and recurrence rates were not significantly different compared to those without any major risk factors for HCC.