Nano-Biphasic Calcium Phosphate Ceramic for the Repair of Bone Defects.

Calcium phosphate bioceramics has recently experienced increased interest in bone reconstruction. Mimicking of natural structure of bone, like the use of nanomaterials, is an attractive approach for generating scaffolds for bone regeneration. The aim of present study was to evaluate the effect of nanonization on the biphasic calcium phosphate (BCP) ceramic in the repair of bone cavities in the canine mandible. A commercial BCP was dry-milled in a high energy planetary ball mill with zirconia balls and container. Three holes (8 mm in diameter) were outlined to the depth of cortical bone of mandibular angle of 5 dogs bilaterally. The first hole (positive control group A, n = 10) was filled in with commercial BCP material. The second hole was loaded with the nanonized BCP (experimental group C, n = 10) and the third one was left untreated (negative control group B, n = 10). The defects were allowed to regenerate for 8 weeks. New bone formation was greater in groups A and C than in B. No difference was seen between group A and group C (P = 0.676). The residual bone material in group C (19.34 ±â€Š8.03) was as much as one-half of that in group A (38.69 ±â€Š7.90%) (P = 0.000). The negative control group B presented the highest amount of soft tissue within the bone defects. The least percentage of marrow space was found in the positive control group (13.23 ±â€Š13.52). Our results depicted that the rate of resorption increased significantly after nanonization even though the nano-sized BCP failed to make a superior regeneration than the ordinary BCP.

Delayed Vesicular Urticarial Dermatosis Due to Apixaban.

Cutaneous adverse drug reactions (cADR) are delayed hypersensitivity reactions that are T-cell mediated. Novel oral anticoagulants, including Factor Xa inhibitors, are increasingly used as therapeutic or prophylactic management of thrombosis and atrial fibrillation. We introduce the case of a 78-year-old woman with no known allergies and a history of atrial fibrillation who was started on apixaban for cerebrovascular accident prophylaxis. Approximately nine days after starting apixaban, she developed a vesicular-urticated erythematous rash initially located on her right upper extremity, progressing to her face. She was evaluated after two weeks for the persistence of symptoms and improved with hydroxyzine and prednisone. Subsequently, she was advised to discontinue and evade all Factor Xa inhibitors, including apixaban, and was switched to warfarin. Naranjo score scale was 5-6. The patient declined skin biopsy and drug challenge. After a month of discontinuation of systemic steroids, patch testing was performed with apixaban, rivaroxaban, and edoxaban, with a negative result. Since this episode, the patient has not had a recurrence of the rash. As far as we know, this is the first case report of a non-severe cADR to apixaban. Even though there are no standardized protocols for diagnosing drug reactions to Factor Xa inhibitors, patch testing at increasing non-irritant concentrations with re-challenge of alternative agents and the suspected offending agent, if possible, should be included in the evaluation of a cADR.

Skin α-Synuclein Aggregation Seeding Activity as a Novel Biomarker for Parkinson Disease.

IMPORTANCE: Deposition of the pathological α-synuclein (αSynP) in the brain is the hallmark of synucleinopathies, including Parkinson disease (PD), Lewy body dementia (LBD), and multiple system atrophy (MSA). Whether real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) assays can sensitively detect skin biomarkers for PD and non-PD synucleinopathies remains unknown. OBJECTIVE: To develop sensitive and specific skin biomarkers for antemortem diagnosis of PD and other synucleinopathies. DESIGN, SETTING, AND PARTICIPANTS: This retrospective and prospective diagnostic study evaluated autopsy and biopsy skin samples from neuropathologically and clinically diagnosed patients with PD and controls without PD. Autopsy skin samples were obtained at 3 medical centers from August 2016 to September 2019, and biopsy samples were collected from 3 institutions from August 2018 to November 2019. Based on neuropathological and clinical diagnoses, 57 cadavers with synucleinopathies and 73 cadavers with nonsynucleinopathies as well as 20 living patients with PD and 21 living controls without PD were included. Specifically, cadavers and participants had PD, LBD, MSA, Alzheimer disease, progressive supranuclear palsy, or corticobasal degeneration or were nonneurodegenerative controls (NNCs). A total of 8 approached biopsy participants either refused to participate in or were excluded from this study due to uncertain clinical diagnosis. Data were analyzed from September 2019 to April 2020. MAIN OUTCOMES AND MEASURES: Skin αSynP seeding activity was analyzed by RT-QuIC and PMCA assays. RESULTS: A total of 160 autopsied skin specimens from 140 cadavers (85 male cadavers [60.7%]; mean [SD] age at death, 76.8 [10.1] years) and 41 antemortem skin biopsies (27 male participants [66%]; mean [SD] age at time of biopsy, 65.3 [9.2] years) were analyzed. RT-QuIC analysis of αSynP seeding activity in autopsy abdominal skin samples from 47 PD cadavers and 43 NNCs revealed 94% sensitivity (95% CI, 85-99) and 98% specificity (95% CI, 89-100). As groups, RT-QuIC also yielded 93% sensitivity (95% CI, 85-97) and 93% specificity (95% CI, 83-97) among 57 cadavers with synucleinopathies (PD, LBD, and MSA) and 73 cadavers without synucleinopathies (Alzheimer disease, progressive supranuclear palsy, corticobasal degeneration, and NNCs). PMCA showed 82% sensitivity (95% CI, 76-88) and 96% specificity (95% CI, 85-100) with autopsy abdominal skin samples from PD cadavers. From posterior cervical and leg skin biopsy tissues from patients with PD and controls without PD, the sensitivity and specificity were 95% (95% CI, 77-100) and 100% (95% CI, 84-100), respectively, for RT-QuIC and 80% (95% CI, 49-96) and 90% (95% CI, 60-100) for PMCA. CONCLUSIONS AND RELEVANCE: This study provides proof-of-concept that skin αSynP seeding activity may serve as a novel biomarker for antemortem diagnoses of PD and other synucleinopathies.