Elevated plasma neurofilament light chain in immune-mediated neurological disorders (IMND) detected by immunomagnetic reduction (IMR).

BACKGROUND: In cases of immune-mediated neurological disorders (IMND), different syndromes are associated with antibodies against neuronal surface antigens, intra-neuronal antigens, astrocytic aquaporin, and gangliosides. These autoantibodies can be pathogenic or connected to neuroinflammation and resulting neuronal injuries. This study aims to identify a blood biomarker that can detect neuronal damage in individuals with IMND. To this end, we use immunomagnetic reduction (IMR) nanobead technology to measure plasma neurofilament light chain (NfL). METHODS: The patients with IMND were enrolled in the Chang Gung Memorial Hospital at Keelung from 2018 to 2023. Seronegative patients were excluded based on the results of antibody tests. The healthy controls (HC) were community-dwelling adults from the Northeastern Taiwan Community Medicine Research Cohort (NTCMRC) conducted by the Community Medicine Research Center of the Keelung CGMH from 2020 to 2022. IMR technique detects magnetic susceptibility via measuring magnetic signal reduction caused by antigen-antibody immunocomplex formation on magnetic nanobeads. The plasma level of NfL was determined by the magnetic susceptibility changes in IMR. RESULTS: The study enrolled 57 IMND patients from the hospital and 73 HC participants from the communities. The plasma NfL was significantly higher in the IMND than in the HC (11.022 ± 2.637 vs. 9.664 ± 2.610 pg/mL, p = 0.004), regardless of age effects on plasma NfL in an analysis of covariance (ANCOVA) (F = 0.720, p = 0.950). In the receiver of operation curve analysis, the area under curve for plasma NfL to discriminate IMND and HC was 0.664 (95% CI = 0.549 to 0.739, p = 0.005). The subgroup analysis of plasma NfL in the IMND patients showed no difference between peripheral immune-mediated neuropathy (IMN) and central immune-mediated encephalomyelitis (IMEM) (11.331 ± 2.895 vs. 10.627 ± 2.260 pg/mL, p = 0.322), nor between tumor and non-tumor IMND (10.784 ± 3.446 vs. 11.093 ± 2.391 pg/mL, p = 0.714). Additionally, the antibody class of ganglioside antibodies in IMN did not have an impact on plasma NfL level (p = 0.857). CONCLUSION: Plasma NfL measurement is a reliable indicator of axonal injuries in patients with IMND. It is equally effective in detecting nerve injuries in inflammatory peripheral neuropathies and central neuroinflammation. The IMR nanobead technology offers a feasible method of detecting plasma NfL, which helps identify axonal injuries in IMND.

The associations between cognitive functions and TSNAX genetic variations in patients with schizophrenia.

BACKGROUND: The translin-associated factor X (TSNAX) gene, located adjacent to the DISC1 gene, has been implicated in schizophrenia. While cognitive impairment determines long-term the functional outcome of schizophrenia, the role of TSNAX in cognitive dysfunction of schizophrenia patients remains elusive. This study aimed to explore the genetic effect of TSNAX on cognitive functions of schizophrenia. METHODS: We recruited 286 chronic schizophrenia patients who had been stabilized with antipsychotics for at least 2 months and genotyped three TSNAX SNPs (rs1630250, rs766288, rs6662926). Clinical symptoms and seven cognitive domains were assessed. The score of cognitive tests was standardized to T score. RESULTS: Clinical symptoms were similar among genotypes of all the three SNPs. The GLM analysis demonstrated that TSNAX genetic polymorphisms influenced cognitive function of schizophrenia patients after adjustment for gender, age, and education. The patients with the rs1630250 C/G genotype performed better than the G/G homozygotes in the Trail Making A (p = 0.034). Those with the rs766288 G/T genotype also performed better than the G/G homozygotes in the Trail Making A (p = 0.012). The patients with the G/G genotype of rs6662926 also performed better than the C/C homozygotes in verbal learning and memory test (p = 0.044). CONCLUSIONS: This study suggests that the TSNAX gene variation may influence the cognitive functions of the patients with schizophrenia.

Functionally graded membrane deposited with PDLLA nanofibers encapsulating doxycycline and enamel matrix derivatives-loaded chitosan nanospheres for alveolar ridge regeneration.

Functionally graded membranes (FGM) with regenerative signals and nanofibrous topography mimicking the native extracellular matrix have been shown to improve the outcome of alveolar ridge regeneration (ARR). This study developed a novel FGM with doxycycline-enamel matrix derivative (EMD) nanofibrous composites deposition to coordinate anti-inflammation and differentiation signals, thus facilitating ARR. Doxycycline-loaded PDLLA nanofibers (PD), EMD-loaded chitosan nanospheres (CE), and CE-embedded PD (CE-PD) were fabricated by electrospinning, deposited on the surfaces of barrier membrane to develop a FGM, and the efficacy was validated by delivering the FGM to regenerate experimental alveolar ridge defects in rats. Results revealed that PD had potent antibacterial capability, and CE-PD allowed sustained release of EMD to promote osteogenesis in vitro. In the alveolar ridge defects, FGM with PD on the outer surface downregulated MMP-8, and wound dehiscence was further reduced with Cbfa1 upregulation in those treated by FGM with CE-PD on the inner surface at 1 week. FGM with CE-PD revealed significantly greater new bone formation and defect fill at 4 weeks. In conclusion, FGM with PD reduced early tissue breakdown and with CE-PD nanofibrous composites accelerated wound healing and facilitated osteogenesis, and thus could be an advantageous strategy for ARR.

The treatment response of barrier membrane with amoxicillin-loaded nanofibers in experimental periodontitis.

BACKGROUND: Infection control is a major determinant of guided tissue regeneration (GTR). This study aims to develop an antibiotic-loaded membrane to assist periodontal repair. METHODS: Poly(D,L-lactic acid) (PDLLA) nanofibers encapsulating amoxicillin (PDLLA-AMX) were fabricated using the electrospinning technique, and their structures, drug encapsulation efficiency, and release characteristics were assessed. The viability and behaviors of periodontal ligament (PDL) cells on nanofibers, and antibacterial capabilities of nanofibers were evaluated in vitro. Early therapeutic efficiency of the antibiotic-loaded membranes was investigated in rats with ligature-induced experimental periodontitis, and the outcomes were evaluated by gene expression, microcomputed tomography imaging, and histology within 7 days of membrane placement. RESULTS: AMX was successfully encapsulated in the PDLLA nanofibers and released in a sustained manner. After initial attachment was achieved, cells stretched out along with the directions of nanofibers. The viability and expression of migration-associated gene of PDL cells were significantly improved, and the growth of Streptococcus sanguinis and Porphyromonas gingivalis was significantly reduced in the PDLLA-AMX group compared with the controls. On PDLLA-AMX-treated sites, wound dehiscence and sulcular inflammation were reduced. Collagen fiber matrix deposition was accelerated with upregulated type I collagen and interleukin-1ß, and downregulated matrix metalloproteinase-8, whereas periodontal bone level and the expressions of vascular endothelial growth factor and core-binding factor subunit alpha-1 were equivalent to conventional membrane treatment. CONCLUSIONS: PDLLA-AMX nanofibers inhibited bacterial growth and promoted the viability and mobility of PDL cells after initial cell attachment. Membranes with PDLLA-AMX nanofibers reduced inflammation and accelerated periodontal repair at an early stage, providing good prospects for the further development of GTR membranes.

Photodissociation dynamics of tryptophan and the implication of asymmetric photolysis.

Photodissociation of amino acid tryptophan in a molecular beam at wavelengths of 212.8 and 193 nm, corresponding to excitation to the second and third absorption bands, was investigated using multimass ion imaging techniques. The respective wavelengths also represent excitation to the edge of a positive circular dichroism band and the center of a negative circular dichroism band of L-tryptophan. Only one dissociation channel was observed at both photolysis wavelengths: C(8)NH(6)CH(2)CHNH(2)COOH-->C(8)NH(6)CH(2)+CHNH(2)COOH. Dissociation rates were found to be 1.3x10(6) and 5x10(6) s(-1) at the respective wavelengths. Comparison to theoretical calculation indicates that dissociation occurs on the ground state after internal conversion. Implication of asymmetric photolysis is discussed.

Eight-year results of hydroxyapatite-coated hip arthroplasty.

Ninety hips in 82 patients using Omnifit hydroxyapatite (HA)-coated prosthesis were followed for at least 7 years. All stems were stable at the final follow-up. However, aseptic loosening was found in 8 cups and 6 of them were revised. Two polyethylene wear were treated with inserts exchanged. The mechanical failure rate was 11.4% and the combined failure rate was 14.3% for HA-coated cup. Four other cups with wear and osteolysis without loosening or pain and 2 cups with polyethylene wear without osteolysis were still under observation. Our findings suggest that hip arthroplasties with HA coating on the smooth surface of a titanium cup is not reliable. The mid-term result of HA-coated stem is as good as that of porous-coated stem.

Human PTH (1-34) induces longitudinal bone growth in rats.

The growth plate is a specialized structure that is responsible for longitudinal bone growth (LGR). Growth plate organization is altered with loading in rats. Parathyroid hormone (PTH) is known to induce mitogenic effect on chondrocytes in vitro. Type I PTH/PTH related peptide (rP) receptor is expressed in growth plate cartilage in rats. We therefore investigated the effect of PTH administration on the organization and longitudinal growth rate of the growth plate in rats. We also investigated the effect of PTH on the changes induced by unloading in the organization and growth of the growth plate. Thirty 6-week-old and 30 15-week-old male Sprague-Dawley rats were randomly assigned to five groups (n = 6 per group), i.e., basal controls, control (i.e., normally loaded), PTH-treated control (i.e., PTH-treated under normal loading), unloaded, and PTH-treated under unloading. PTH-treated animals received human PTH (1-34) at a dose of 80 microg/kg per day five times per week for 3 weeks, for the duration of unloading. In young loaded rats treated with the systemic administration of PTH, growth plate thickness, chondrocyte number, and LGR were increased in the proximal tibiae compared with findings in young loaded rats without PTH administration. Hindlimb unloading induced a reduction in growth plate thickness, chondrocyte number, and LGR. In young rats, systemic administration of PTH partly prevented these changes induced by unloading. These preventive effects of PTH were observed only in young rats; not in adult rats. These results show that the systemic administration of PTH stimulates longitudinal bone growth, and diminishes the reduction in growth plate growth induced by unloading in young rats.