Posterior-Stabilized Antibiotic Cement Articulating Spacer With Endoskeleton-Reinforced Cam Reduces Rate of Post-Cam Mechanical Complications in Prosthetic Knee Infection: A Preliminary Study.

BACKGROUND: Posterior-stabilized antibiotic cement articulating spacers (PS spacers) reduce spacer mechanical complications in prosthetic knee infections (PKIs); however, joint dislocation after femoral cam fracture has been reported. We hypothesized that the rate of post-cam mechanical complications is lower in PS spacers with an endoskeleton-reinforced cam. METHOD: A retrospective study of PKIs using PS spacers with or without a Kirschner wire-reinforced cam (K-PS or nK-PS spacers, respectively) was conducted between 2015 and 2019. The rates of post-cam mechanical complications and reoperation, as well as risk factors for post or cam failure, were analyzed. RESULTS: The cohort included 118 nK-PS and 49 K-PS spacers. All patients were followed up for 2 years. The rate of joint subluxation/dislocation after femoral cam fracture was lower in K-PS (0%) than in nK-PS spacers (17.8%; P = .002). The reoperation rate for spacer mechanical complications was lower in K-PS (0%) than in nK-PS spacers (11.9%; P = .008). The identified risk factors for femoral cam fractures were body mass index ≥25 kg/m2, femoral spacer size ≤2, and surgical volume ≤12 resection arthroplasties per year. CONCLUSION: This preliminary study highlights that K-PS spacers have a lower rate of post-cam mechanical complications than nK-PS spacers. We recommend the use of PS spacers with endoskeleton-reinforced cam when treating PKIs performed by surgeons with lower surgical volumes, especially in patients with higher body mass index and smaller femoral spacer sizes.

Cruciate-Retaining vs Posterior-Stabilized Antibiotic Cement Articulating Spacers for Two-Stage Revision of Prosthetic Knee Infection: A Retrospective Cohort Study.

BACKGROUND: Antibiotic cement articulating spacers are recommended during 2-stage revision for prosthetic knee infection because of increased range of motion (ROM) and improved function; however, spacer mechanical complications have been reported. We aimed to determine the association between different constraints of articulating spacers and the rate of complications and infection eradication, functional outcomes, and ROM. METHODS: A retrospective study of prosthetic knee infection using cruciate-retaining (CR) or posterior-stabilized (PS) spacers was conducted between 2011 and 2018. The rate of spacer mechanical complications, infection eradication after reimplantation and reoperation, Hospital of Special Surgery (HSS) knee score, and ROM during the interim stage were analyzed. All patients were regularly followed up for 2 years. RESULTS: One hundred forty-one patients were included, with 66 CR and 75 PS spacers. Overall mechanical complication rate was lower in PS (9.3%) than in CR spacers (45.5%) (P < .001), especially in joint dislocation (1.3% vs 30.3%, respectively, P < .001). Overall reoperation rate was lower in PS (16.0%) than in CR spacers (36.4%) (P < .001), especially for mechanical complications (1.3% vs 24.2%, respectively, P < .001). HSS knee score was higher in PS (72.3) than in CR spacers (63.8) (P < .001). ROM was greater in PS (90.3°) than in CR spacers (80.6°) (P = .005), especially at maximum flexion (102.4° vs 89.6°, respectively, P = .003). Infection eradication was comparable between the spacers. CONCLUSION: Both spacers can control infection; however, PS spacers had a lower rate of mechanical complications and reoperation, better HSS knee scores, and greater ROM than CR spacers.

Anthropometric Factors on Safe Distances between Popliteal Vessels to the Femur for Cerclage Wiring of the Distal Femoral Fracture: A Magnetic Resonance Imaging Study.

Background and Objectives: The proximity of the popliteal vessels in the distal femur may increase the risk of iatrogenic vascular injury during cerclage wiring. In this study, the closest location and distance of the popliteal vessels to the femur was examined using magnetic resonance imaging (MRI). The associations between anthropometric factors and the distance that would guide the placement of wires safely during surgery were also identified. Materials and Methods: We reviewed adult knee magnetic resonance images and recorded: (1) the relation and the shortest horizontal distance (d-H) from the femoral cortex to the popliteal vessels in axial images and (2) the vertical distance (d-V) from the adductor tubercle to the axial level of the d-H values in coronal images. The effects of anthropometric factors (sex, age, body height, body weight, body mass index, thigh circumference, femoral length and femoral width) on these distances were analysed. Results: Analysis of 206 knee magnetic resonance images revealed that the closet locations of popliteal vessels were at the posteromedial aspect of the femur. The d-H and d-V were 7.38 ± 3.22 mm and 57.01 ± 11.14 mm, respectively, and were both shorter in women than in men (p < 0.001). Multivariate analysis identified thigh circumference and femoral length as the most influential factors for the d-H and d-V, respectively (p < 0.001). Linear regression demonstrated a strong positive linear correlation between the thigh circumference and the d-H and between the femoral length and the d-V (Pearson's r = 0.891 and 0.806, respectively (p < 0.001)). Conclusions: The closet location and distance of the popliteal vessels to the femur provide useful information for wire placement during distal femoral fracture surgery while minimising the risk of vascular injury. Given that patients with a smaller thigh circumference and a shorter femoral length are more likely to have a smaller d-H and a shorter d-V, respectively, cautious measures should be taken in such cases.

Diagnosis of painful cemented vertebrae from failed vertebroplasty: modified dynamic radiographs play an important role.

PURPOSE: The diagnosis of painful cemented vertebrae resulting from failed PV is not clearly defined in literature. This report evaluates the effectiveness of modified dynamic radiographs in diagnosing painful cemented vertebrae resulting from failed PV. METHODS: From January 2011 to June 2015, 345 patients with a total of 399 VCFs underwent PV at our institution. Among the 345 patients, 27 patients underwent repeated PV at the cemented vertebrae because of persisting or recurrent pain after vertebroplasty. The prevertebroplasty examinations included routine radiographs, modified dynamic radiographs, and MRI. Kyphotic angles and the anterior vertebral body height (AVBH) were measured. The image findings in routine radiographs, modified dynamic radiographs, and MRI were compared. Finally, a visual analog scale was used to measure the outcome. RESULTS: The patients ranged in age from 67 to 90 years. MRI revealed a moderate amount of fluid (definite diagnosis of refracture) in the cemented vertebrae in seven patients, bone edema without fluid in nine patients, and bone edema with minimal fluid in ten patients. The rate of diagnosis of painful cemented vertebrae according to MRI was 27% (7/26). The difference in the kyphotic angle between sitting and supine cross-table lateral radiographs was -9.36° ± 5.20° (P < 0.001). The difference in AVBH was 8.08 ± 3.21 mm (P < 0.001). All 27 patients were confirmed to have dynamic mobility according to the modified dynamic radiographs. CONCLUSIONS: When the diagnosis of painful cemented vertebrae is questionable, modified dynamic radiographs can help diagnose painful cemented vertebrae resulting from failed PV.

Structural characteristics of the nonallosteric human cytosolic malic enzyme.

Human cytosolic NADP(+)-dependent malic enzyme (c-NADP-ME) is neither a cooperative nor an allosteric enzyme, whereas mitochondrial NAD(P)(+)-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by fumarate. This study examines the molecular basis for the different allosteric properties and quaternary structural stability of m-NAD(P)-ME and c-NADP-ME. Multiple residues corresponding to the fumarate-binding site were mutated in human c-NADP-ME to correspond to those found in human m-NAD(P)-ME. Additionally, the crystal structure of the apo (ligand-free) human c-NADP-ME conformation was determined. Kinetic studies indicated no significant difference between the wild-type and mutant enzymes in Km,NADP, Km,malate, and kcat. A chimeric enzyme, [51-105]_c-NADP-ME, was designed to include the putative fumarate-binding site of m-NAD(P)-ME at the dimer interface of c-NADP-ME; however, this chimera remained nonallosteric. In addition to fumarate activation, the quaternary structural stability of c-NADP-ME and m-NAD(P)-ME is quite different; c-NADP-ME is a stable tetramer, whereas m-NAD(P)-ME exists in equilibrium between a dimer and a tetramer. The quaternary structures for the S57K/N59E/E73K/S102D and S57K/N59E/E73K/S102D/H74K/D78P/D80E/D87G mutants of c-NADP-ME are tetrameric, whereas the K57S/E59N/K73E/D102S m-NAD(P)-ME quadruple mutant is primarily monomeric with some dimer formation. These results strongly suggest that the structural features near the fumarate-binding site and the dimer interface are highly related to the quaternary structural stability of c-NADP-ME and m-NAD(P)-ME. In this study, we attempt to delineate the structural features governing the fumarate-induced allosteric activation of malic enzyme.

Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study.

Oseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van't Hoff equation were - 77.49 kJ/mol, -176.54 J/(mol∙K), and - 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.

Medullary-Sparing Antibiotic Cement Articulating Spacer Reduces the Rate of Mechanical Complications in Advanced Septic Hip Arthritis: A Retrospective Cohort Study.

Antibiotic cement articulating spacers eradicate infection during a two-stage revision for advanced septic hip arthritis (ASHA); however, mechanical complications have been reported. We hypothesized that the rate of mechanical complications would be lower in medullary-sparing (MS) than in non-medullary-sparing (n-MS) articulating spacers. A retrospective study of ASHA using n-MS or MS spacers was conducted between 1999 and 2019. The rate of mechanical complications and reoperation and risk factors for mechanical complications were analyzed. The cohort included 71 n-MS and 36 MS spacers. All patients were followed up for 2 years. The rate of spacer dislocation was lower in MS (0%) than in n-MS spacers (14.1%; p = 0.014). The reoperation rate for mechanical complications was lower in MS (0%) than in n-MS spacers (12.7%; p = 0.019). The rate of a diaphyseal stem during reimplantation was lower in MS (0%) than in n-MS spacers (19.4%; p = 0.002). The identified risk factors for n-MS spacer dislocation were postoperative under-restored femoral head diameter ≥3 mm, femoral offset ≥3 mm, and surgical volume (≤6 resection arthroplasties per year). Both spacers controlled infection. However, MS spacers had a lower spacer dislocation and reoperation rate and avoided the diaphyseal stem during reimplantation. We recommend using MS spacers to restore native femoral head diameter and femoral offset when ASHA is treated by surgeons with lower surgical volumes.

Effect of Surgeon Volume on Mechanical Complications after Resection Arthroplasty with Articulating Spacer.

Two-stage revision with an antibiotic-loaded cement articulating spacer is a standard treatment for chronic prosthetic knee infection (PKI); however, mechanical complications can occur during the spacer period. There is limited evidence on the association between surgeon volume and mechanical complications after resection arthroplasty (RA) using an articulating spacer. This study aimed to compare the rates of mechanical complications and reoperation after RA with articulating spacers by surgeons with high volumes (HV) and low volumes (LV) of RA performed and analyzed the risk factors for mechanical failure. The retrospective study investigated 203 patients treated with PKIs who underwent RA with articulating spacers and were divided according to the number of RAs performed by the surgeons: HV (≥14 RAs/year) or LV (<14 RAs/year). Rates of mechanical complications and reoperations were compared. Risk factors for mechanical complications were analyzed. Of the 203 patients, 105 and 98 were treated by two HV and six LV surgeons, respectively. The mechanical complication rate was lower in HV surgeons (3.8%) than in LV surgeons (36.7%) (p < 0.001). The reoperation rate for mechanical complications was lower in HV surgeons (0.9%) than in LV surgeons (24.5%) (p < 0.001). Additionally, 47.2% of patients required hinge knees after mechanical spacer failure. Medial proximal tibial angle < 87°, recurvatum angle > 5°, and the use of a tibial spacer without a cement stem extension were risk factors for mechanical complications. Based on these findings, we made the following three conclusions: (1) HV surgeons had a lower rate of mechanical complications and reoperation than LV surgeons; (2) mechanical complications increased the level of constraint in final revision knee arthroplasty; and (3) all surgeons should avoid tibial spacer varus malalignment and recurvatum deformity and always use a cement stem extension with a tibial spacer.

Analysis of flavonoids by graphene-based surface-assisted laser desorption/ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a simple and fast technique for the analysis of large biomolecules but is not suitable for the detection of low molecular weight molecules and compounds, such as flavonoids and phenylpropanoids, mainly due to the lack of an appropriate matrix. Flavonoids and phenylpropanoids, such as coumarin and its derivatives, have attracted much attention recently because of their pharmacological activities and putative therapeutic benefits. In this study, we developed a quick and simple LDI-TOF MS method for the detection of flavonoids and the derivatives of coumarin. Analytes were spotted onto a matrix of graphene-based nanoparticles and then analyzed by LDI-TOF MS in the negative ion mode. Analysis of the sensitivity and effect of different graphene-based nanoparticles including graphene, graphene oxide, and reduced graphene oxide on desorption/ionization of analytes showed that graphene oxide was the most suitable matrix. Moreover, we found that graphene oxide sheets of larger lateral size resulted in better desorption/ionization efficiency. Overall, we show that graphene oxide is a useful matrix for the analysis of flavonoids and the derivatives of coumarin by LDI-TOF MS in the negative ion mode.

Arthroscopy-Assisted Reduction and Internal Fixation versus Open Reduction and Internal Fixation for Glenoid Fracture with Scapular Involvement: A Retrospective Cohort Study.

BACKGROUND: We investigated the superiority of arthroscopy-assisted reduction and internal fixation (ARIF) to open reduction and internal fixation (ORIF) for treating glenoid fracture with scapular involvement. METHODS: We retrospectively enrolled patients with glenoid fracture who underwent ARIF or ORIF from 2010-2020. Radiographic outcomes were assessed, and clinical outcomes (active range of motion [ROM], visual analog scale [VAS], Constant, and Disabilities of the Arm, Shoulder and Hand [DASH]) were evaluated 12 months postoperatively. RESULTS: Forty-four patients with Ideberg type II-VI glenoid fractures (ARIF: 20; ORIF: 24; follow-up 12-22 months) were included. Union was achieved in all patients. Active ROM values were comparable between the approaches. Constant and DASH scores were non-significantly better with ARIF (90.9 ± 9.2 vs. 86.6 ± 18.1 [p = 0.341] and 6.8 ± 9.4 vs. 9.3 ± 21.3 [p = 0.626], respectively). However, VAS scores were significantly lower with ARIF (1.5 ± 0.6 vs. 2.7 ± 1.4, p = 0.001). Associated intra-articular lesions (articular depressions [80%], superior labral anterior-posterior tear [20%], labral tears [30%]) were found in most ARIF cases and were repaired during ARIF. CONCLUSIONS: For glenoid fracture with scapular involvement, ARIF allows accurate diagnosis of fracture pattern and the management of associated intra-articular lesions, with better pain control outcomes than ORIF. Thus, arthroscopy-assistant surgery should be considered in patient with glenoid fracture.

Percutaneous Endoscopic Surgery Alone to Treat Severe Infectious Spondylodiscitis in the Thoracolumbar Spine: A Reparative Mechanism of Spontaneous Spinal Arthrodesis.

BACKGROUND: Infective spondylodiscitis has been treated solely with antibiotics based on the pathogen identified. Surgical intervention was used in cases of unidentified pathogens, failed antibiotic treatment, neurological deficit, or instability. The standard surgical procedure was debridement and interbody fusion with a bone graft through the anterior approach, followed by posterior instrumentation. Recently, percutaneous endoscopic surgery has been proven to be safe and effective for treating infectious spondylodiscitis. The results of endoscopy surgery treatment alone for infectious spondylodiscitis with severe bony destruction were analyzed in this study. OBJECTIVE: To describe the clinical and radiological outcomes in patients with infectious spondylodiscitis and severe bony destruction, who were treated with minimally invasive endoscopic surgery alone. STUDY DESIGN: Retrospective observational study (Institutional Review Board: CMUH 105-REC2-101). SETTING: An inpatient surgery center. METHODS: The study included 24 patients with infectious spondylodiscitis and severe bony destruction treated with endoscopy surgery. The patients were treated according to the endoscopic surgical protocol and were followed up for at least 5 years. A retrospective chart review was conducted to evaluate the locations, symptoms and signs, comorbidity, pain scale, and functional outcome. Laboratory data, such as erythrocyte sedimentation rate and C-reactive protein level, and clinical outcomes, including the pain scale, visual analogue scale, and functional score of Oswestry disability index, were recorded. All patients underwent a preoperative magnetic resonance imaging (MRI) scan and were carefully reviewed and classified based on the severity, including endplate erosion, bone edema (low T1, high T2), loss of vertebral height, paravertebral inflammation, paravertebral abscess, and epidural abscess. All patients underwent a plain film follow-up at 3, 6, 9, 12, and 18 months after surgery and computed tomography at 12 months postoperatively. RESULTS: The comorbidities of patients were categorized according to the Charlson Comorbidity Index. The results revealed 10 lesions on the thoracic or upper lumbar spine (between T10 and L3) and 14 on the lower lumbar spine (between L3 and S1). Bone destruction as a result of severe infection and loss of disc height was observed in most cases. During the final follow-up, no significant changes were observed in the sagittal alignment, and a kyphotic angle change of less than 10° was observed in 20 cases. Syndesmophyte formation along the anterior longitudinal ligament (ALL), paravertebral syndesmophyte formation, intervertebral bony fusion, and bony ankylosis of the facet joints in the form of osteophyte formation and fusion were noted. No posterior instrumentation surgery was performed for instability in our case series. LIMITATIONS: This was a retrospective observational clinical case series with small sample size. CONCLUSIONS: A trend of spontaneous spinal arthrodesis, including syndesmophyte formation along the ALL, paravertebral ligaments, direct intervertebral bone growth, and bony ankylosis of the facet joint were observed after a minimally invasive endoscopy treatment for infectious spondylodiscitis. The stability of the 3 columns resulted in segmental stability, which prevented the progression of the kyphotic deformity. Percutaneous endoscopic surgery is safe and effective for treating infectious spondylodiscitis even in patients with severe bony destruction.

Desmoplastic tumour-associated stroma versus neural tissue in central nervous system metastasis: effects of different microenvironments on tumour growth.

AIMS: Interactions between tumour cells and extracellular matrix (ECM) are critical in the metastatic cascade. We compared effects of desmoplastic stroma versus neural tissue on central nervous system (CNS) metastasis. METHODS AND RESULTS: Using integrins (ECM receptors), ECM (fibronectin, laminin and collagen IV) and CD31 and vascular endothelial growth factor (VEGF) for angiogenesis, this study examined immunohistochemically 69 consecutive cases of CNS metastases. In contrast to low-level expression in tumour-embedded neural tissue, ECM [fibronectin (71%), laminin γ-1 (79%) and collagen IV (92%)] and CD31-positive microvascular densities (33 versus 4 vessels/field) were significantly richer in desmoplastic tumour stroma, which was present in 90% (53 of 59) of carcinomas, 100% (five of five) of malignant melanomas and 100% (two of two) of sarcomas. Collagen IV expression in tumour stroma was correlated with the expression of fibronectin (P = 0.013) and laminin (P = 0.034) and with infiltrative tumour edges (P = 0.005); fibronectin-positive tumour stroma was correlated with a higher microvascular density (P = 0.015). In addition, tumour cells expressed integrins (∼75%) and laminin (84%) more frequently than VEGF (23%), and tumour expression of laminin was correlated with the presence of desmoplastic stroma (P = 0.006). Interestingly, laminin-positive tumour stroma was a worse prognosticator (P = 0.072). CONCLUSIONS: ECM- and vascular-rich stroma is important in tumour growth, which underlies therapeutic strategies targeting tumour-associated stroma.

Theoretical calculation of the OH vibrational overtone spectra of 1-n alkane diols (n = 2-4): origin of disappearing hydrogen-bonded OH peak.

In this theoretical study, we simulated the vibrational overtone spectrum of ethylene glycol (EG), 1-3 propanediol (PD), and 1-4 butanediol (BD). Using the local mode model along with the potential energy curve and dipole moment function calculated by B3LYP/6-31+G(d,p) and QCISD/6-311++G(3df,3pd), we obtained the theoretical peak position and integrated absorption coefficient. Furthermore, the vibrational spectra was simulated using a Voigt function using homogeneous and inhomogenous width obtained from quantum chemical calculation methods. Previously, Howard and Kjaergaard recorded the second and third overtone photoacoustic spectra of the three aforementioned alkane diols in the gas phase and observed that the intramolecular hydrogen bonded OH peak becomes difficult to observe as the intramolecular hydrogen bonding strength increased, that is, as the chain length was increased. In this paper we show that the disappearance of the hydrogen-bonded OH peak for the OH stretching overtone excitation for BD is partly due to the increase in homogeneous width due to the increase in the hydrogen bond strength and partly due to the decrease in the relative population of the intramolecular hydrogen-bonded conformers as the chain length is increased. This latter feature is a consequence of the unfavorable strained geometry needed to form the intramolecular hydrogen bond in longer alkane chains.

Theoretical calculation of the OH vibrational overtone spectra of 1,5-pentanediol and 1,6-hexanediol.

It is well-known that intramolecular hydrogen bonding affects the relative energetics of conformers, as well as the OH stretching peak positions, intensities, and width. In this study we simulated the Δv(OH) = 3, 4 overtone spectra of 1,5-pentanediol (PeD) and 1,6-hexanediol (HD) using the peak positions, intensities, and width calculated from the B3LYP/6-31+G(d,p) method. Furthermore, room temperature free energy calculations were performed using B3LYP/6-31+G(d,p) MP2/6-31+G(d,p), and MP2/6-311++G(3df,3pd) to obtain the relative population of the conformers. From the calculation of 109 and 381 distinct conformers for PeD and HD, respectively, we find that for these long chain diols the intramolecular hydrogen bonded conformers are not the most dominant conformation at room temperature. This is in stark contrast with shorter chain diols such as ethylene glycol for which the hydrogen bonded conformer dominates the population at room temperature. On the other hand, we found that the correlation between the hydrogen bonded OH red shift versus the homogeneous width, Γ = 0.0155(Δω)(1.36), which was derived for shorter chain diols, is valid even for these longer chain diols. We also showed that the intramolecular hydrogen bonded OH initially decays through the CCOH torsion and COH bending mode no matter how long the alkanediol chain length is for 1,n-alkanediols for n up to 6.

RTN4B-mediated suppression of Sirtuin 2 activity ameliorates ß-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model.

Sirtuin 2 (SIRT2) is an NAD+ dependent deacetylase that is the most abundant sirtuin protein in the brain. Accumulating evidence revealed the role of SIRT2 in a wide range of biological processes and age-related diseases. However, the pivotal mechanism of SIRT2 played in Alzheimer's disease (AD) remains unknown. Here, we report that pharmacological inactivation of SIRT2 has a beneficial effect in AD. The deacetylase inhibitor of SIRT2 rescued the cognitive impairment in amyloid precursor protein/presenilin 1 transgenic mouse (APP/PS1 mouse), and the BACE1 cleavage was weakened to reduce the ß-amyloid (Aß) production in the hippocampus. Moreover, we firstly identified that Reticulon 4B (RTN4B) played a crucial role between SIRT2/BACE1 regulation in AD. RTN4B, as a deacetylation substrate for SIRT2, the deacetylation by SIRT2 drived the ubiquitination and degradation of RTN4B and then the disturbed RTN4B interacted with and influenced the expression of BACE1. When we overexpressed RTN4B in neurons of the hippocampus in the AD mouse model, the abnormal Aß accumulation and cognitive impairment were ameliorated, consistent with the results of SIRT2 inhibition in vivo. Moreover, we showed that the regulatory effect of SIRT2 on BACE1 is dependent on RTN4B. When RTN4B was knocked down, the effects of SIRT2 inhibition on the BACE1 level, Aß pathology, and AD-liked behaviors were also blocked. Collectively, we provide evidence that SIRT2 may be a potential target for AD; the new found SIRT2/RTN4B/BACE1 pathological pathway is one of the critical mechanisms for the improvement of SIRT2 on AD.

Two Cases of De Novo Pathological Gambling Associated With Aripiprazole.

OBJECTIVES: Pathological gambling can be potentiated by treatment with dopamine agonists. Aripiprazole, bearing a partial agonist activity at dopamine D2 and D3 receptors, has also been linked to such a behavioral aberration, usually on subjects predisposed with tendency of impulsive or addictive behaviors. METHODS: Review of patient's medical records and literature review. RESULTS: Two young patients' pathological gambling emerged simply due to exposure to aripiprazole, neither related to manic or psychotic symptoms nor with history of addictive or impulsive behaviors. Their pathological gambling disappeared soon after switching aripiprazole to other antipsychotics. One patient has tested such a relationship by reexposure to aripiprazole while his compulsion to gamble recurred. CONCLUSIONS: In addition to previously recognized risk factors, pathological gambling might occur in young patients whose history did not reveal an addictive tendency while they were sensitive to the pharmacological effect, as well as adverse effects, of psychotropic agents.

A prospective study of the factors associated with life quality during medical internship.

BACKGROUND: Medical interns' quality of life (QOL) are related to patient care quality, but the specific factors responsible for interns' QOL have not been well studied. Herein we presented this nationwide, prospective study to examine the impact of working hours restrictions on the QOL among medical interns. METHODS: The study recruited 295 medical interns (age: 25.3 ± 2.1, male: 68.1%) from all the 8 medical colleges in Taiwan during the 2012-2013 academic years. Subjects were assessed for QOL by brief version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF) and the 9-item Patient Health Questionnaire (PHQ-9) before and every 3 months during their internship. We also investigated their demographic data, working hours, workload characteristics, such as specialties of internship rotation, acceptance of new patients after 24-hour, and no 24-hour off within 7 days, and self-reported patient related burnout. We used generalized estimation equation to delineate the change of WHOQOL-BREF and PHQ-9 scores during internship. We used multivariate regression analysis to examine the associated factors of QOL. RESULTS: WHOQOL-BREF score significantly decreased during internship (baseline: 60.0 ± 9.7, 53.7 ± 9.3 at 3 months, then remained at 55 after 9 months). Acceptance of new patients after 24 hours of continuous duty (ß = -2.089), no 24-hour off within 7 days (ß = -1.748), score of patient related burnout (ß = -2.50), and PHQ-9 depression score (ß = -1.02) were associated with lower WHOQOL-BREF score. Working hours was not significantly associated with the QOL (p = .6268). CONCLUSIONS: Our findings revealed interns' QOL significantly decreased during internship. Acceptance of new patients after 24-hour of continuous duty and patient related burnout predominantly impacted interns' QOL and depression more than working hours did.

A preliminary study of the novel antibiotic-loaded cement computer-aided design-articulating spacer for the treatment of periprosthetic knee infection.

BACKGROUND: In comparison to static spacers, articulating spacers have been shown to result in a similar infection eradication rate in two-stage revision of periprosthetic knee infections. However, the optimal construct for articulating spacers has not been identified yet. The aim of this study was to present a preliminary result of treatment for periprosthetic knee infection using a novel computer-aided design (CAD)-articulating spacer. METHODS: We retrospectively reviewed 32 consecutive cases of chronic periprosthetic knee infection occurring from January 2015 to December 2015. In these cases, we used an antibiotic-loaded, optimized CAD-articulating spacer based on the retrieved knee prosthesis. Evaluation included infection eradication rate, the Hospital of Special Surgery (HSS) knee score, range of motion (ROM), and spacer-related mechanical complications. All cases were regularly followed-up for 2 years minimum. RESULTS: Twenty-eight of 32 patients (87.5%) had infection eradication; 18 patients (56.3%) received reimplantation successfully. The mean interval between spacer insertion and reimplantation was 8.8 months (range 4.0-12.5 months). The mean HSS knee score and ROM significantly increased during each interval (p < 0.0001 for both). The mean HSS knee scores were 31.2 (range 20-48) at initial visit, 65.4 (range 60-78.8) at 1 month after spacer insertion, and 84.2 (range 78-90) at 3 months after reimplantation (p < 0.0001). The mean ROM were 72.0° (range 15-100°), 85.6° (range 35-110°), and 102.0° (range 80-122°), respectively (p = 0.002). Two (6.3%) spacer-related mechanical complications occurred. CONCLUSIONS: The CAD-articulating spacer in two-staged revision of periprosthetic knee infection significantly controlled infection, improved clinical outcomes, increased ROM, and decreased mechanical complications in the preliminary study. Further larger clinical studies are needed to confirm the findings presented here.

Comparison of genomes of three Xanthomonas oryzae bacteriophages.

BACKGROUND: Xp10 and OP1 are phages of Xanthomonas oryzae pv. oryzae (Xoo), the causative agent of bacterial leaf blight in rice plants, which were isolated in 1967 in Taiwan and in 1954 in Japan, respectively. We recently isolated the Xoo phage Xop411. RESULTS: The linear Xop411 genome (44,520 bp, 58 ORFs) sequenced here is 147 bp longer than that of Xp10 (60 ORFs) and 735 bp longer than that of OP1 (59 ORFs). The G+C contents of OP1 (51%) and Xop411 and Xp10 (52% each) are less than that of the host (65%). The 9-bp 3'-overhangs (5'-GGACAGTCT-3') in Xop411 and Xp10 are absent from OP1. More of the deduced Xop411 proteins share higher degrees of identity with Xp10 than with OP1 proteins, while the right end of the genomes of Xp10 and OP1, containing all predicted promoters, share stronger homology. Xop411, Xp10, and OP1 contain 8, 7, and 6 freestanding HNH endonuclease genes, respectively. These genes can be classified into five groups depending on their possession of the HNH domain (HNN or HNH type) and/or AP2 domain in intact or truncated forms. While the HNN-AP2 type endonuclease genes dispersed in the genome, the HNH type endonuclease genes, each with a unique copy, were located within the same genome context. Mass spectrometry and N-terminal sequencing showed nine Xop411 coat proteins, among which three were identified, six were assigned as coat proteins (4) and conserved phage proteins (2) in Xp10. The major coat protein, in which only the N-terminal methionine is removed, appears to exist in oligomeric forms containing 2 to 6 subunits. The three phages exhibit different patterns of domain duplication in the N-terminus of the tail fiber, which are involved in determination of the host range. Many short repeated sequences are present in and around the duplicated domains. CONCLUSION: Geographical separation may have confined lateral gene transfer among the Xoo phages. The HNN-AP2 type endonucleases were more likely to transfer their genes randomly in the genome and may degenerate after successful transmission. Some repeated sequences may be involved in duplication/loss of the domains in the tail fiber genes.

Probing the Roles of Calcium-Binding Sites during the Folding of Human Peptidylarginine Deiminase 4.

Our recent studies of peptidylarginine deiminase 4 (PAD4) demonstrate that its non-catalytic Ca2+-binding sites play a crucial role in the assembly of the correct geometry of the enzyme. Here, we examined the folding mechanism of PAD4 and the role of Ca2+ ions in the folding pathway. Multiple mutations were introduced into the calcium-binding sites, and these mutants were termed the Ca1_site, Ca2_site, Ca3_site, Ca4_site and Ca5_site mutants. Our data indicate that during the unfolding process, the PAD4 dimer first dissociates into monomers, and the monomers then undergo a three-state denaturation process via an intermediate state formation. In addition, Ca2+ ions assist in stabilizing the folding intermediate, particularly through binding to the Ca3_site and Ca4_site to ensure the correct and active conformation of PAD4. The binding of calcium ions to the Ca1_site and Ca2_site is directly involved in the catalytic action of the enzyme. Finally, this study proposes a model for the folding of PAD4. The nascent polypeptide chains of PAD4 are first folded into monomeric intermediate states, then continue to fold into monomers, and ultimately assemble into a functional and dimeric PAD4 enzyme, and cellular Ca2+ ions may be the critical factor governing the interchange.