Treatment of irreducible atlantoaxial dislocation by bony deformity osteotomy, remodeling, releasing, and plate fixating through transoral approach.

OBJECTIVE: Investigate a novel method for treating irreducible atlantoaxial dislocation (IAAD) or with basilar invagination (BI) by bony deformity osteotomy, remodeling, releasing, and plate fixating through transoral approach. METHOD: From March 2015 to December 2019, 213 consecutive patients diagnosed as IAAD/BI were treated with transoral bony deformity remodeling and releasing combined with plate fixation. The main clinical symptoms include neck pain, headache, numbness of the limbs, weakness, unstable walking, inflexible hand-held objects, and sphincter dysfunction. The bony factors that impact reduction were divided into as follows: type A1 (sloping of upper facet joint in C2), type A2 (osteophyte in lateral mass joints between C1 and C2), type A3 (ball-and-socket deformity of lateral mass joint), type A4 (vertical interlocking between lateral mass joints of C1-C2), type A5 (regional bone fusion in lateral mass joints), type B1 (bony factor hindering reduction between the atlas-dens gap), type B2 (uncinate odontoid deformity), and type B3 (hypertrophic odontoid deformity). All of them were treated with bony deformity osteotomy, remodeling, and releasing techs. RESULT: The operation time was 144 [Formula: see text] 25 min with blood loss of 102 [Formula: see text] 35 ml. The average pre-operative ADI improved from 7.5 [Formula: see text] 3.2 mm pre-surgery to 2.5 [Formula: see text] 1.5 mm post-surgery (p < 0.05). The average VDI improved from 12.3 [Formula: see text] 4.8 mm pre-surgery to 3.3 [Formula: see text] 2.1 mm post-surgery (p < 0.05). The average pre-operative CMA improved from 115 [Formula: see text] 25° pre-surgery to 158 [Formula: see text] 21° post-surgery (p < 0.05); the pre-operative CAA changed from 101 [Formula: see text] 28° pre-surgery to 141 [Formula: see text] 10° post-surgery. After the operation, the clinic symptoms improved, and the JOA score improved from 9.3 [Formula: see text] 2.8 pre-operatively to 13.8 [Formula: see text] 2.5 in the sixth months of follow-up. CONCLUSION: In addition to soft tissue factors, bony obstruction was another important factor impeding atlantoaxial reduction. Transoral bony deformity osteotomy, remodeling, releasing combined with plate fixating was effective in treating IAAD/BI with bony obstruction factors.

High-Sensitivity Flexible Piezoresistive Pressure Sensor Using PDMS/MWNTS Nanocomposite Membrane Reinforced with Isopropanol for Pulse Detection.

Flexible pressure sensors with high sensitivity and good linearity are in high demand to meet the long-term and accurate detection requirements for pulse detection. In this study, we propose a composite membrane pressure sensor using polydimethylsiloxane (PDMS) and multiwalled carbon nanotubes (MWNTS) reinforced with isopropanol prepared by solution blending and a self-made 3D-printed mold. The device doped with isopropanol had a higher sensitivity and linearity owning to the construction of additional conductive paths. The optimal conditions for realizing a high-performance pressure sensor are a multiwalled carbon nanotube mass ratio of 7% and a composite membrane thickness of 490 µm. The membrane achieves a high linear sensitivity of -57.07 kΩ∙kPa-1 and a linear fitting correlation coefficient of 98.78% in the 0.13~5.2 kPa pressure range corresponding to pulse detection. Clearly, this device has great potential for application in pulse detection.

Nanoscale Coordination Polymers for Synergistic NO and Chemodynamic Therapy of Liver Cancer.

Nitric oxide (NO) induces a multitude of antitumor activities, encompassing the induction of apoptosis, sensitization to chemo-, radio-, or immune-therapy, and inhibition of metastasis, drug resistance, angiogenesis, and hypoxia, thus attracting much attention in the area of cancer intervention. To improve the precise targeting and treatment efficacy of NO, a glutathione (GSH)-sensitive NO donor (1,5-bis[(l-proline-1-yl)diazen-1-ium-1,2-diol- O2-yl]-2,4-dinitrobenzene, BPDB) coordinates with iron ions to form the nanoscale coordination polymer (NCP) via a simple precipitation and then partial ion exchange process. The obtained Fe(II)-BNCP shows desirable solubility, biocompatibility, and circulation stability. Quick NO release triggered by high concentrations of GSH in tumor cells improves the specificity of NO release in situ, thus avoiding side effects in other tissues. Meanwhile, under high concentrations of H2O2 in tumors, Fe2+ ions in BPDB-based NCP, named Fe(II)-BNCP, exert Fenton activity to generate hydroxyl radicals (·OH), which is the main contribution for chemodynamic therapy (CDT). In addition, ·O2- generated by the Haber-Weiss reaction of Fe2+ ions with H2O2 can quickly react with NO to produce peroxynitrite anion (ONOO-) that is more cytotoxic than ·O2- or NO only. This synergistic NO-CDT effect has been proved to retard the tumor growth in Heps xenograft ICR mouse models. This work not only implements a synergistic effect of NO-CDT therapy but also offers a simple and efficient strategy to construct a coordination polymer nanomedicine via rationally designed prodrug molecules such as NO donors.

Treatment of basilar invagination with atlantoaxial dislocation: atlantoaxial joint distraction and fixation with transoral atlantoaxial reduction plate (TARP) without odontoidectomy.

PURPOSE: Although direct transoral decompression and one-stage posterior instrumentation can obtain satisfactory cord decompression for the treatment of basilar invagination with atlantoaxial dislocation, surgical injuries run high as combinative anterior-posterior approaches were necessary. Furthermore, the complications will rise notably when involvement of dens and/or clivus in the decompression necessitates relatively complicated surgical techniques. First initiated in 2005, transoral atlantoaxial reduction plate (TARP) works as an internal fixation for the treatment of basilar invagination with irreducible atlantoaxial dislocation. Therefore, this article aimed to describe several operative experiences about this approach, which has delivered successful decompression, fixation and fusion. METHODS: 21 consecutive patients with basilar invagination underwent the TARP operation. The pre- and postoperative medulla-cervical angles were measured and compared. The JOA scores of spinal cord function were calculated pre- and post-operatively. 20 cases (20/21) were followed up to average 12.5 months. RESULTS: Symptoms of all the 20 cases were relieved in different degrees. The postoperative imaging showed the odontoid processes obtained ideal reduction and the internal fixators were all in good position. The medulla-cervical angle was correctd from an average (± standard deviation) 128.7° + 11.9° (n = 20) before surgery to 156.5° + 8.1° (n = 20) after surgery (P < 0.01). The average preoperative and postoperative Japaneses Orthopedic Association scores were 11.25 (n = 20) and 15.9 (n = 20), respectively, indicating 76 % improvement. Screw-loosening was observed in one patient due to severe osteoporosis. After a revised operation with a TARP in another size, the neurological symptoms showed no obvious improvements. Then the treatment was terminated. CONCLUSIONS: The TARP operation and intra-operative traction could reduce the odontoid process superiorly migrating into the foramen magnum, directly ease the ventral compression of spinal cord, and fix the reduced atlantoaxial joints through a single transoral approach without the need of a posterior operation. In this stury, 21 patients were evaluated and 20 did well with TARP operation. The preliminary clinical result was satisfactory.

Constructing high-strength nano-micro fibrous woven scaffolds with native-like anisotropic structure and immunoregulatory function for tendon repair and regeneration.

Tendon injuries are common debilitating musculoskeletal diseases with high treatment expenditure in sports medicine. The development of tendon-biomimetic scaffolds may be promising for improving the unsatisfactory clinical outcomes of traditional therapies. In this study, we combined an advanced electrospun nanofiber yarn-generating technique with a traditional textile manufacturing strategy to fabricate innovative nano-micro fibrous woven scaffolds with tendon-like anisotropic structure and high-strength mechanical properties for the treatment of large-size tendon injury. Electrospun nanofiber yarns made from pure poly L-lactic acid (PLLA) or silk fibroin (SF)/PLLA blend were fabricated, and their mechanical properties matched and even exceeded those of commercial PLLA microfiber yarns. The PLLA or SF/PLLA nanofiber yarns were then employed as weft yarns interlaced with commercial PLLA microfiber yarns as warp yarns to generate two new types of nanofibrous scaffolds (nmPLLA and nmSF/PLLA) with a plain-weaving structure. Woven scaffolds made from pure PLLA microfiber yarns (both weft and warp directions) (mmPLLA) were used as controls.In vitroexperiments showed that the nmSF/PLLA woven scaffold with aligned fibrous topography significantly promoted cell adhesion, elongation, proliferation, and phenotypic maintenance of tenocytes compared with mmPLLA and nmPLLA woven scaffolds. Moreover, the nmSF/PLLA woven scaffold exhibited the strongest immunoregulatory functions and effectively modulated macrophages towards the M2 phenotype.In vivoexperiments revealed that the nmSF/PLLA woven scaffold notably facilitated Achilles tendon regeneration with improved structure by macroscopic, histological, and ultrastructural observations six months after surgery, compared with the other two groups. More importantly, the regenerated tissue in the nmSF/PLLA group had excellent biomechanical properties comparable to those of the native tendon. Overall, our study provides an innovative biological-free strategy with ready-to-use features, which presents great potential for clinical translation for damaged tendon repair.

Exploratory analysis to enhance operational efficiency of new patient screenings.

OBJECTIVE: The aims of this study were to 1) evaluate patient demographic data for new patient exams (NPE) and 2) analyze lead response time for checked-in and no-show appointments in predoctoral clinics in a dental school. METHODS: The data for the study were collected from the predoctoral clinics at Tufts University School of Dental Medicine (TUSDM) for patients with NPE appointments with American Dental Association's (ADA) diagnostic code of D100. A total of 26,826 appointments and 24,419 unique patients were reviewed from January 1, 2015 to December 31, 2019. Patient demographic variables such as age, gender, zip codes, and lead response time were analyzed. RESULTS: From 26,826 total number of appointments, 10,454 appointments were categorized as no-show appointments (38.97%). In the no-show appointments, the sex distribution was 59.93% female and 40.07% male, and in checked-in category, the sex distribution was 53.75% female and 46.25% male. As the lead response time increased over 5 days, the no-show rate increased to 49.79%. Approximately 55% of the entire NPE was from Greater Boston area. CONCLUSION: The association between lead time and no-show rate was shown that when lead time was reduced, no-show rate decreased. By identifying the no-show appointments and lead time, schools and clinics can improve operational efficiency, reduce financial loss, and maintain continuation of care by supporting patients who need access to care and creating secondary automated recall system to maximize communication and chair use.

Self-conjugated protective antigen elicits strong and durable protective antibody response against anthrax.

Anthrax is an acute and highly lethal disease caused by Bacillus anthracis. Protective antigen (PA) is the primary candidate antigen for the anthrax vaccines. However, PA suffers from poor immunogenicity with short-term anti-PA antibody response. High effectiveness, durable immunity, and minimal risk are required for development of an effective anthrax vaccine. In the present study, PA was self-conjugated by 8-arm polyethylene glycol (PEG) and further by thioester chemistry. As a result, 3-5 PA molecules were covalently conjugated and functioned as an antigen delivery system. The conjugate (PA-PEG) could maintain the structural properties of PA and increase the thermal stability of PA. PA-PEG could elicit a robust anti-PA IgG and neutralization antibody response in the magnitude and quality. The antibodies could be largely maintained for 180 days after three immunizations of PA-PEG. PA-PEG effectively stimulated the maturation of dendritic cell and rapidly induced the germinal center (GC) reaction. The percentages of the GC B-cells and T follicular helper (Tfh) cells were thus significantly augmented. The inflammatory response elicited by PA-PEG was comparable to those by PBS and PA. Therefore, PA-PEG is expected as an effective anthrax vaccine candidate with durable immunoprotection against anthrax.

Atlantoaxial Joint Distraction for the Treatment of Basilar Invagination: Clinical Outcomes and Radiographic Evaluation.

OBJECTIVE: To investigate the causes of partial remission in patients with basilar invagination (BI) and irreducible atlantoaxial dislocation (IAAD) treated with transoral atlantoaxial reduction plate (TARP) without odontoidectomy and quantify the distance of odontoid descent. METHODS: Between August 2010 and July 2012, 22 consecutive patients with BI with IAAD who underwent TARP surgery were reviewed. The preoperative and postoperative radiographic parameters were evaluated. Follow-up data and the symptom treatment interval (STI), defined as the interval between the onset of symptoms and surgical treatment, were assessed. Neurological function was evaluated as neurologic improvement, defined as ([Postoperative Japanese Orthopedic Association (JOA) score] - [Preoperative JOA score])/(17 - [Preoperative JOA score]). The patients were assigned to group A (<50%) or group B (≥50%) based on their level of neurologic improvement. RESULTS: All 22 patients improved clinically to varying degrees. The mean preoperative STI was 105.6 ± 67.6 months for group A and 45.3 ± 46.7 months for group B (P < 0.05). There were no significant between-group differences in follow-up (P > 0.05) or with respect to radiographic parameters (P > 0.05). Persistent brainstem compression was observed in 1 patient, whose symptoms were not adequately relieved after revision surgery (transoral odontoidectomy and posterior decompression and fusion). No fixation failure was observed. CONCLUSIONS: Descent of the odontoid process is useful for treating basilar invagination. TARP surgery without odontoidectomy may pull the dens caudally and ventrally to achieve sufficient decompression of the spinal cord. Neurologic improvement may be associated with STI.

[Epidemiologic study on STD/HIV infections among tin mining workers in Gejiu, Yunnan province].

OBJECTIVE: To estimate human immunodeficiency virus (HIV)/sexually transmitted diseases (STDs) related knowledge, the prevalence and risk factors for HIV/STDs among tin miners in Gejiu, Yunnan Province. METHODS: A cross-sectional study was conducted in tin miners working at 5 mining regions from March to June 2006 in Gejiu City, Yunnan Province. A total of 1796 miners were enrolled in the study, and a standardized questionnaire was administered probing socio-demographic factors, knowledge of HIV/STDs and sexual behavior. 7 ml-volume venous blood and 15 ml urine specimens were collected for HIV/STDs testing. RESULTS: Twelve participants [0.7%] (12/1760) were identified HIV positive. While, the positive proportions for syphilis, herpes simplex virus type-2 (HSV-2), Neisseria gonorrhea and Chlamydia trachoma were 1.8% (31/1760), 9.6% (169/1760), 0.8% (14/1773), 4.8% (85/1773), respectively. The total prevalence of STDs was 14.9% (264/1776). Factors associated with HIV infection were illegal drug use (adjusted OR = 17.8; 95% CI: 4.0 - 78.8), frequencies of visiting female sex workers in the past twelve months (adjusted OR = 8.7; 95% CI: 1.9 - 39.0), tattoos (adjusted OR = 6.6; 95% CI: 1.8 - 24.0), surgical operation experiences (adjusted OR = 6.0; 95% CI: 1.6 - 22.5) and toothbrush sharing (adjusted OR = 5.6; 95% CI: 1.0 - 31.3). Factors associated with STDs infection were race (adjusted OR = 2.0; 95% CI: 1.5 - 2.7), age (adjusted OR = 1.7; 95% CI: 1.0 - 2.9), illegal drug use (adjusted OR = 2.3; 95% CI: 1.0 - 5.2), living with spouses (adjusted OR = 1.4; 95% CI: 1.1 - 1.9) and visiting female sex workers (adjusted OR = 1.9; 95% CI: 1.4 - 2.6). Only 4.1% (49/1201) of respondents aware the correct transmission routes of HIV. 21.6% (339/1569) of the miners who had previous sexual experience self-reported visiting female sex workers. CONCLUSION: HIV and other STDs are highly prevalent amongst miners in this region. In addition, the awareness of HIV/STDs is low and multiple routes of HIV transmission, such as heterosexual intercourse and IDU, were also observed in these study subject. HIV/STDs interventions should therefore be reinforced among the miners in this region.

Simultaneous lipid and content mixing assays for in vitro reconstitution studies of synaptic vesicle fusion.

This protocol describes reconstitution assays to study how the neurotransmitter release machinery triggers Ca2+-dependent synaptic vesicle fusion. The assays monitor fusion between proteoliposomes containing the synaptic vesicle SNARE synaptobrevin (with or without the Ca2+ sensor synaptotagmin-1) and proteoliposomes initially containing the plasma membrane SNAREs syntaxin-1 and soluble NSF attachment protein (SNAP)-25. Lipid mixing (from fluorescence de-quenching of Marina-Blue-labeled lipids) and content mixing (from development of fluorescence resonance energy transfer (FRET) between phycoerythrin-biotin (PhycoE-Biotin) and Cy5-streptavidin trapped in the two proteoliposome populations) are measured simultaneously to ensure that true, nonleaky membrane fusion is monitored. This protocol is based on a method developed to study yeast vacuolar fusion. In contrast to other protocols used to study the release machinery, this assay incorporates N-ethylmaleimide sensitive factor (NSF) and α-SNAP, which disassemble syntaxin-1 and SNAP-25 heterodimers. As a result, fusion requires Munc18-1, which binds to the released syntaxin-1, and Munc13-1, which, together with Munc18-1, orchestrates SNARE complex assembly. The protocol can be readily adapted to investigation of other types of intracellular membrane fusion by using appropriate alternative proteins. Total time required for one round of the assay is 4 d.

Treatment of Basilar Invagination With Klippel-Feil Syndrome: Atlantoaxial Joint Distraction and Fixation With Transoral Atlantoaxial Reduction Plate.

BACKGROUND: Klippel-Feil syndrome (KFS) is characterized by congenital vertebral fusion of the cervical spine and a wide spectrum of associated anomalies. In patients with KFS with basilar invagination (BI), compression of the brainstem and upper cervical cord results in neurological deficits, and decompression and occipitocervical reconstruction are required. The highly varied anatomy of KFS makes a posterior occipitocervical fixation strategy challenging. For these patients, the transoral atlantoaxial reduction plate (TARP) operation is an optimal option to perform a direct anterior fixation to achieve stabilization. OBJECTIVE: To evaluate the effectiveness of TARP internal fixation for the treatment of BI with KFS. METHODS: Ten consecutive patients with BI and KFS who underwent TARP reduction and fixation from 2010 to 2012 were reviewed. Clinical assessment and image measurements were performed preoperatively and at the most recent follow-up. Nine patients (9/10) were followed for an average of 31.44 months. RESULTS: Symptoms were alleviated in 9 of 9 patients (100.00%). The odontoid process was ideally corrected with the TARP system. The mean clivus canal angle improved from 124° preoperatively to 152° postoperatively. The average preoperative and postoperative Japanese Orthopedic Association scores were 10.56 (n = 9) and 14.67 (n = 9), respectively, indicating 63.82% improvement. There was bony bridge catenation on the computed tomography scans and no evidence of hardware failure at 6 months. CONCLUSION: The TARP operation is effective and safe for treating patients with BI with KFS. The midterm clinical results were satisfactory.

Transoral approach for revision surgery of os odontoideum with atlantoaxial dislocation.

Revision surgery for os odontoideum with irreducible atlantoaxial dislocation with a transoral approach is not commonly seen. Typically, management of this type of atlantoaxial dislocation is through posterior fixation and fusion or transoral decompression and posterior fusion. This report describes revision surgery in a patient with os odontoideum who was treated with a transoral approach. A 50-year-old man was diagnosed with os odontoideum and atlantoaxial dislocation in 2007 and was treated surgically with posterior occipitocervical internal fixation and fusion. In 2012, he had recurrence of neck pain and numbness of the limbs. Neurologic function was grade D according to the standard neurologic classification of spinal cord injury from the American Spinal Injury Association. Because this was a revision surgery, the internal fixation implant was removed through a posterior approach and a transoral approach was used for release, reduction, internal fixation, and fusion. Two 6-mm cages filled with autogenous bone were introduced into the lateral mass spaces for bony fusion and distraction, and 2 cervical compressive mini-frames were used for fixation. Complete atlantoaxial reduction and decompression of the spinal cord were achieved. The patient reported improvement of symptoms after surgery. Movement of the extremities increased from grade III force to grade V, and neurologic status improved from American Spinal Injury Association grade D to grade E. A transoral approach for release, reduction, bony fusion, and fixation could be an effective procedure for the treatment of os odontoideum with irreducible atlantoaxial dislocation. It provides a new option for bony fusion and internal fixation of the atlantoaxial joint.