Biochemical and structural characterization of an inositol pyrophosphate kinase from a giant virus.

Kinases that synthesize inositol phosphates (IPs) and pyrophosphates (PP-IPs) control numerous biological processes in eukaryotic cells. Herein, we extend this cellular signaling repertoire to viruses. We have biochemically and structurally characterized a minimalist inositol phosphate kinase (i.e., TvIPK) encoded by Terrestrivirus, a nucleocytoplasmic large ("giant") DNA virus (NCLDV). We show that TvIPK can synthesize inositol pyrophosphates from a range of scyllo- and myo-IPs, both in vitro and when expressed in yeast cells. We present multiple crystal structures of enzyme/substrate/nucleotide complexes with individual resolutions from 1.95 to 2.6 Å. We find a heart-shaped ligand binding pocket comprising an array of positively charged and flexible side chains, underlying the observed substrate diversity. A crucial arginine residue in a conserved "G-loop" orients the γ-phosphate of ATP to allow substrate pyrophosphorylation. We highlight additional conserved catalytic and architectural features in TvIPK, and support their importance through site-directed mutagenesis. We propose that NCLDV inositol phosphate kinases may have assisted evolution of inositol pyrophosphate signaling, and we discuss the potential biogeochemical significance of TvIPK in soil niches.

Longer peripheral-track lesions are associated with instability after arthroscopic Bankart repair.

BACKGROUND: The glenoid track concept has enabled the categorization of Hill-Sachs lesions (HSLs) into on-track lesions and off-track lesions. Furthermore, among the on-track lesions, further categorization has been established based on the distance from the medial edge of the Hill-Sachs lesion to the medial edge of the glenoid track, into peripheral-track lesions and central-track lesions. Recent studies on peripheral-track lesions and central-track lesions within the glenoid track have shown inconsistencies in failure rates, which deserves further investigation. METHODS: A retrospective cohort comparison of patients who underwent arthroscopic Bankart repair between 2015 and 2020 was performed. 102 patients with peripheral-track HSLs were included. The patients were divided into 2 groups based on the results of the postoperative apprehension test: the apprehension positive group (n = 30), and the apprehension negative group (n = 72). Using preoperative computed tomography (CT) and an image reconstruction program, 3-dimensional (3D) images were segmented to calculate the length, width, depth, and distance of the HSLs. A multivariate logistic regression was used to determine the risk factors of recurrence, for which odds ratio (OR) and 95% confidence interval (CI) were provided. RESULTS: A multivariate logistic regression analysis revealed that the length of the peripheral-track HSLs was a significant independent predictor of failure in this study. (OR 1.380; 95% CI 1.170-1.627; P < .001). The receiver operating characteristics curve (ROC) demonstrated a predictive power (area under the curve = 0.841) and a threshold value of 14.2 mm. CONCLUSION: Length was the only risk factor for the recurrent instability of peripheral-track HSLs after ABR. In the context of surgical decision-making, utilizing the glenoid track concept, medical practitioners may need to evaluate instability by considering the length as a continuous factor, while differentiating between peripheral-track and central-track classifications.

Intraoperative fluoroscopy reduces the variability in femoral tunnel placement during single-bundle anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the effect of using intraoperative fluoroscopy on femoral and tibial tunnel positioning variability in single-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 80 consecutive patients with single-bundle ACL reconstruction between 2014 and 2016 were retrospectively reviewed. Among them, 40 underwent ACL reconstruction without fluoroscopy (non-fluoroscopy group) and 40 underwent fluoroscopy-assisted ACL reconstruction (fluoroscopy group). Femoral and tibial tunnel locations were evaluated using a standardized grid system with three-dimensional computed tomography images. Femoral and tibial tunnel location variability was compared between the groups. RESULTS: The operation time was longer in the fluoroscopy group than in the non-fluoroscopy group (61.3 ± 5.2 min vs. 55.5 ± 4.5 min, p < 0.001). In the fluoroscopy group, a guide pin was repositioned in 16 (40%) cases on the femoral side and 2 (5%) cases on the tibial side. No significant difference in the femoral tunnel location was observed between the fluoroscopy and non-fluoroscopy groups (anterior-posterior plane, 29.0% ± 3.2% vs. 30.0% ± 6.1%; proximal-distal plane, 30.8% ± 4.8% vs. 29.4% ± 8.3%; all parameters, n.s.); variability was significantly lower in the fluoroscopy group (p < 0.001 for both anterior-posterior and proximal-distal planes). No significant difference in the tibial tunnel location and variability was observed between the fluoroscopy and non-fluoroscopy groups (medial-lateral plane, 45.8% ± 2.0% vs. 46.6% ± 2.4%; anterior-posterior plane, 31.2% ± 4.0% vs. 31.0% ± 5.4%) (all parameters, n.s.). CONCLUSIONS: Tunnel positioning with fluoroscopic assistance is feasible and effective in achieving consistency in femoral tunnel placement despite a slightly longer operation time. Intraoperative fluoroscopy can be helpful in cases wherein identifying anatomical landmarks on arthroscopy was difficult or for surgeons with less experience who performed ACL reconstruction. LEVEL OF EVIDENCE: IV.

Second-look arthroscopic findings and clinical outcomes of meniscal repair with concomitant anterior cruciate ligament reconstruction: comparison of suture and meniscus fixation device.

INTRODUCTION: The purpose of this study was to evaluate the healing rate of repaired meniscus and functional outcomes of patients who received all-inside meniscal repair using sutures or devices with concomitant arthroscopic anterior cruciate ligament (ACL) reconstruction. MATERIALS AND METHODS: Among the patients who have ACL tear and posterior horn tear of medial or lateral meniscus, 61 knees who received all-inside repair using sutures (suture group, n = 28) or meniscal fixation devices (device group, n = 33) with concomitant ACL reconstruction during the period from January 2012 to December 2015, followed by second-look arthroscopy, were retrospectively reviewed. Healing status of the repair site was assessed by second-look arthroscopy. Through the clinical assessment, clinical success (negative medial joint line tenderness, no history of locking or recurrent effusion, and negative McMurray test) rate of the repaired meniscus and functional outcomes (International Knee Documentation Committee subjective score and Lysholm knee score) was evaluated. RESULTS: In a comparison of healing status of repaired meniscus evaluated by second-look arthroscopy, suture group had 23 cases of complete healing (82.1%), 4 cases of incomplete healing (14.3%), and 1 case of failure (3.6%). Device group had 18 cases of complete healing (54.5%), 4 cases of incomplete healing (24.2%), and 7 cases of failure (21.2%) (p = 0.048). Clinical success rate of the meniscal repair was 89.3% (25 cases) and 81.8% (27 cases) in suture group and device group, respectively (p = 0.488). No significant difference of functional outcomes was observed between the two groups (p > 0.05, both parameters). CONCLUSIONS: Among the patients who received meniscal repair with concomitant ACL reconstruction, suture group showed better healing status of repaired meniscus based on the second-look arthroscopy than device group. However, no significant between-group difference of clinical success rate and functional outcomes was observed.

Whole-Cell Photoenzymatic Cascades to Synthesize Long-Chain Aliphatic Amines and Esters from Renewable Fatty Acids.

Long-chain aliphatic amines such as (S,Z)-heptadec-9-en-7-amine and 9-aminoheptadecane were synthesized from ricinoleic acid and oleic acid, respectively, by whole-cell cascade reactions using the combination of an alcohol dehydrogenase (ADH) from Micrococcus luteus, an engineered amine transaminase from Vibrio fluvialis (Vf-ATA), and a photoactivated decarboxylase from Chlorella variabilis NC64A (Cv-FAP) in a one-pot process. In addition, long chain aliphatic esters such as 10-(heptanoyloxy)dec-8-ene and octylnonanoate were prepared from ricinoleic acid and oleic acid, respectively, by using the combination of the ADH, a Baeyer-Villiger monooxygenase variant from Pseudomonas putida KT2440, and the Cv-FAP. The target compounds were produced at rates of up to 37 U g-1 dry cells with conversions up to 90 %. Therefore, this study contributes to the preparation of industrially relevant long-chain aliphatic chiral amines and esters from renewable fatty acid resources.

Effect of Femoral Tunnel Position on Stability and Clinical Outcomes After Single-Bundle Anterior Cruciate Ligament Reconstruction Using the Outside-In Technique.

PURPOSE: To evaluate the effects of the femoral tunnel location in the femoral footprint of the anterior cruciate ligament (ACL) on postoperative knee stability and clinical outcomes after ACL reconstruction (ACLR) using the outside-in technique. METHODS: From December 2012 to August 2014, ACLR was performed using the outside-in technique in 137 patients. Among these patients, those who had a follow-up period of over 2 years were retrospectively reviewed. A total of 102 patients met the inclusion criteria. The relative location of the femoral tunnel in the lateral condyle was evaluated as a percentage using the standardized grid system on a 3-dimensional computed tomography image. Each patient was then classified into the anterior group, center group (anteroposterior plane, 29.3% ± 3.5%), or posterior group depending on the location of the femoral tunnel. Knee laxity was evaluated using a GNRB knee arthrometer, stress radiography, and the pivot-shift test. From a clinical perspective, patient-reported outcomes (International Knee Documentation Committee subjective form and Lysholm knee score) were then evaluated. RESULTS: Of 102 patients, 31 (30.4%) were assigned to the anterior group, 46 (45.1%) were assigned to the center group, and 25 (24.5%) were assigned to the posterior group. Postoperative side-to-side differences, which were measured using stress radiographs and the GNRB arthrometer, were significantly smaller in the posterior group (1.7 ± 0.6 mm and 1.5 ± 0.5 mm, respectively) than in the center group (2.3 ± 0.9 mm and 2.2 ± 2.8 mm, respectively) and anterior group (2.4 ± 0.7 mm and 2.4 ± 1.3 mm, respectively) (P = .002 for stress radiography and P = .002 for GNRB arthrometer). No significant between-group differences were observed in the pivot-shift test results and patient-reported outcomes among the 3 groups. CONCLUSIONS: The location of the femoral tunnel in the anatomic ACL footprint did not affect postoperative stability and clinical outcomes in the case of ACLR using the outside-in technique. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Clinical and Radiologic Outcomes of Patients With Lax Healing After Medial Meniscal Root Repair: Comparison With Subtotal Meniscectomy.

PURPOSE: To compare radiologic and clinical outcomes between patients who underwent medial meniscus posterior root tear (MMPRT) repair and were subsequently classified as having lax healing based on second-look arthroscopy and patients who underwent subtotal meniscectomy for an MMPRT. METHODS: The patients who received pullout repair or subtotal meniscectomy due to MMPRT between January 2011 and December 2014 were retrospectively reviewed. Among the patients who underwent MMPRT repair, those whose lax healing of the repair site was confirmed by second-look arthroscopy (repair/lax healing group) and among the patients who received subtotal meniscectomy, those who have varus deformity of <5° and a Kellgren-Lawrence grade of ≤2 (meniscectomy group) were included in the study population. Medial joint space width, Kellgren-Lawrence grade, International Knee Documentation Committee Subjective Knee Evaluation Form score, and Lysholm Knee score were used for radiologic and clinical assessment. RESULTS: The meniscectomy group included 24 patients (average follow-up, 37.2 months), and the repair/lax healing group included 21 patients (average follow-up, 39.2 months). The 2 groups showed improved patient-reported outcomes postoperatively (P < .001). However, medial joint space width (P < .001) became narrow and Kellgren-Lawrence grade (P = .002 and P = .005, respectively) worsened. Comparison of the radiologic outcomes between the 2 groups revealed that the repair/lax healing group had less Kellgren-Lawrence grade progression than the meniscectomy group (P = .014). The grade progressed by ≥2 grades in 4 patients (16.7%) and 0 patients in the meniscectomy and repair/lax healing groups, respectively (P < .001). CONCLUSIONS: Although the repair/lax healing group showed improved functional outcomes on short-term follow-up, arthritic change progressed radiologically. Nevertheless, the repair/lax healing group showed better radiologic outcomes than the meniscectomy group, despite lax healing of the repair site. However, because of the small number of cases in this study, the results of this study could be associated with potential for type II or ß errors. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Long-term outcomes of unicompartmental knee arthroplasty in patients requiring high flexion: an average 10-year follow-up study.

INTRODUCTION: To evaluate the long-term survival of unicompartmental knee arthroplasty (UKA) in the Asian population and assess differences in clinical outcomes between mobile- and fixed-bearing UKA. MATERIALS AND METHODS: Among 111 cases of UKA that were performed by 1 surgeon from January 2002 to December 2009, we retrospectively reviewed 96 cases (36 mobile-bearing, 62 fixed-bearing) for this study. We examined cause of revision or failure, type of reoperation/revision, and duration from the surgery date to the revision upon reviewing the medical record. Survival analysis was conducted using the Kaplan-Meier method. Functional outcomes were evaluated based on range of motion and patient-reported outcome (PRO) measures (Knee Injury and Osteoarthritis Outcome Score) for cases with at least 8 years of follow-up (average, 10.2 years). RESULTS: Overall, the 10-year survival was 88% [95% confidence interval (CI) 0.81-0.95], and the estimated mean survival time was 13.4 years (95% CI 12.5-14.2). In a comparison of survival between the mobile- and fixed-bearing groups, the former had a 10-year survival of 85% (95% CI, 0.72-0.97) and an estimated mean survival time of 13.5 years (95% CI 12.2-14.7) and the latter had a 10-year survival of 90% (95% CI 0.82-0.99) and an estimated mean survival time of 13.4 years (95% CI 12.3-14.4). Thus, there was no significant difference in survival between the two groups (log-rank test, p = 0.718). In addition, no significant difference in functional outcomes was observed between the two groups (p > 0.05 for all). CONCLUSIONS: UKA performed in the Asian population showed a relatively good functional outcome and survival rate at an average 10-year follow-up. No difference in survival and PROs was observed according to the bearing type. Although the present study demonstrated a good survival rate, similar to that in other Western studies, further studies investigating the impact of the Asian lifestyle on the long-term survival of UKA is necessary.

Unusual truncation of N-acylated peptoids under acidic conditions.

The terminal amino groups of peptoids have often been protected with acetyl groups to improve cell permeability and therapeutic potential, and to prevent the poisoning of the catalysts in organometallic reactions. Interestingly, the unusual truncation of the terminal peptoid unit has sometimes been encountered when the acetylated linear peptoids were treated with a TFA cleavage cocktail. In this study, we systematically investigated the electronic effects of acyl groups on the truncation of N-acylated peptoids to rationalize the formation of the deleted peptoids and to establish an appropriate strategy for preventing such undesired truncation.

Temporal Muscle Thickness and Sarcopenia Components in Healthy Adults, Validated through Allgeun Diagnostic Tool.

Sarcopenia, characterized by progressive muscle loss and functional decline, poses significant risks, including falls, impaired daily activities, and increased mortality. We developed Allgeun, a novel device that measures handgrip strength, muscle mass, and physical performance. This study aimed to investigate whether temporal muscle thickness (TMT) could be used as a sarcopenia marker and to evaluate the usability of Allgeun. This prospective study enrolled 28 participants without medical or neurological disorders. They underwent three-dimensional T1-weighted imaging using a 3 Tesla magnetic resonance imaging scanner. TMT was measured based on T1-weighted images by a board-certified neuroradiologist. Allgeun was used to measure the following three key components of sarcopenia: muscle strength (handgrip strength), muscle mass (calf and thigh circumference), and physical performance (five times the chair stand test). Correlation analysis was conducted between TMT and the results of the handgrip strength, calf and thigh circumferences, and chair stand tests. There were moderate positive correlations between TMT and calf circumference (r = 0.413, p = 0.029), thigh circumference (r = 0.486, p = 0.008), and handgrip strength (r = 0.444, p = 0.018). However, no significant correlation was observed between TMT and physical performance (r = -0.000, p = 0.998). Our findings underscore TMT's potential as an indicator of sarcopenia, particularly regarding muscle mass and strength. Additionally, we demonstrated that the new device, Allgeun, is useful for screening and diagnosing the severity of sarcopenia.

Risk of Infection After Septic and Aseptic Revision Total Knee Arthroplasty: A Systematic Review.

BACKGROUND: The causes of primary total knee arthroplasty (TKA) failure can be divided into septic and aseptic etiologies. It is unclear whether the etiology affects the infection rate after revision TKA. This systematic review was conducted to evaluate whether there is a difference in infection rates between septic and aseptic revision TKA. We hypothesized that infection rates would be higher after septic revision TKA. METHODS: The PubMed and Embase databases and the Cochrane Library were searched to find studies evaluating infection rates following septic and aseptic revision TKA. We included studies that compared the postoperative infection rates of a group that received revision TKA for aseptic failure and a group that received 1- or 2-stage revision TKA for septic failure. Studies on re-revision TKA and on revision surgery after partial knee arthroplasty were excluded, as were studies of debridement, antibiotics, and implant retention (DAIR). RESULTS: Twelve studies were included in this systematic review. In studies in which 1- or 2-stage revision TKA was performed for septic failure, septic revision TKA had a significantly higher infection rate than aseptic revision TKA (odds ratio [OR], 6.83; 95% confidence interval [CI], 1.54 to 30.33; p = 0.01). Similarly, in studies in which 2-stage revision TKA was performed for septic failure, septic revision TKA had a significantly higher infection rate than aseptic revision TKA (OR, 4.14; 95% CI, 2.33 to 7.36; p < 0.00001). In the comparison of revision TKA for aseptic loosening and septic revision TKA, septic revision TKA had a higher infection rate than aseptic revision TKA (OR, 4.45; 95% CI, 2.28 to 8.70; p < 0.0001). CONCLUSIONS: Overall, septic revision TKA had a higher infection rate than aseptic revision TKA. Even when 2-stage revision TKA was performed for septic failure, the infection rate was higher after septic revision TKA than after aseptic revision. Surgeons should explain the relatively high infection rates to patients undergoing revision TKA for septic failure of their primary joint replacement. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Ethambutol-mediated cell wall modification in recombinant Corynebacterium glutamicum increases the biotransformation rates of cyclohexanone derivatives.

The effects of structural modification of cell wall on the biotransformation capability by recombinant Corynebacterium glutamicum cells, expressing the chnB gene encoding cyclohexanone monooxygenase of Acinetobacter calcoaceticus NCIMB 9871, were investigated. Baeyer-Villiger oxygenation of 2-(2'-acetoxyethyl) cyclohexanone (MW 170 Da) into R-7-(2'-acetoxyethyl)-2-oxepanone was used as a model reaction. The whole-cell biotransformation followed Michaelis-Menten kinetics. The V (max) and K (S) values were estimated as 96.8 U g(-1) of dry cells and 0.98 mM, respectively. The V (max) was comparable with that of cyclohexanone oxygenation, whereas the K (S) was almost eightfold higher. The K (S) value of 2-(2'-acetoxyethyl) cyclohexanone oxygenation was reduced by ca. 30% via altering the cell envelop structure of C. glutamicum with ethambutol, which inhibits arabinosyl transferases involved in the biosynthesis of cell wall arabinogalactan and mycolate layers. The higher whole-cell biotransformation rate was also observed in the oxygenation of ethyl 2-cyclohexanone acetate upon ethambutol treatment of the recombinant C. glutamicum. Therefore, it was assumed that the biotransformation efficiency of C. glutamicum-based biocatalysts, with respect to medium- to large-sized lipophilic organic substrates (MW > ca. 170), can be enhanced by engineering their cell wall outer layers, which are known to function as a formidable barrier to lipophilic molecules.

Biomechanical Comparative Study for Osteosynthesis of Pauwels Type III Femoral Neck Fractures: Conventional Devices versus Novel Fixed Angle Devices.

Purpose: Osteosynthesis has been recommended for treatment of Pauwels type III femoral neck fractures in young patients. However, no implant of choice has been reported so far. This study was conducted in order to compare the fixation stability of two conventional fixation methods with three different novel fixed angle devices in this type of fracture. Materials and Methods: A total of 25 composite femurs (4th Generation Saw bone; Pacific Research Laboratories, USA) corresponding to human bone were used. Pauwels type III fracture type was uniformly reproduced. Specimens were fixed with a cannulated screw, cannulated screw with cable, and Intertan nail, dynamic hip screw, and IKEY nail. Measurement of failure loads and the rotational change of the femoral head fragment was performed for evaluation of fixation stability. Results: All implants were compared with cannulated screw and dynmaic hip screw. No meaningful improvement was observed for the cannulated screw with cable compared with the cannulated screw and dynamic hip screw. Meaningful improvement in load-to-failure and y-rotation and z-rotation was observed for both the Intertan nail and IKEY nail compared with the cannulated screw. However, compared with the dynamic hip screw, only the IKEY nail showed improvement in the same profile but the Intertan nail did not. Conclusion: Among novel fixed angle devices, meaningful improvement was observed for the IKEY nail compared with conventional implants. Strengths of this implant include biomechanical stability and simplicity of surgical technique, indicating that it may be another good option for osteosynthesis of Pauwels type III femoral neck fractures.

Novel RPL13 Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia.

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant in RPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia. In vitro studies on patient-derived dermal fibroblasts harboring RPL13 missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p < 0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p = 0.007) and attenuated global translation (p = 0.017). In line with the human phenotype, our rpl13 mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum of RPL13 mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generated rpl13 mutant zebrafish model corroborates the role of eL13 in skeletogenesis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Synthetic GPI array to study antitoxic malaria response.

Parasite glycosylphosphatidylinositol (GPI) is an important toxin in malaria disease, and people living in malaria-endemic regions often produce high levels of anti-GPI antibodies. The natural anti-GPI antibody response needs to be understood to aid the design of an efficient carbohydrate-based antitoxin vaccine. We present a versatile approach based on a synthetic GPI glycan array to correlate anti-GPI antibody levels and protection from severe malaria.

Synthetic glycosylphosphatidylinositol microarray reveals differential antibody levels and fine specificities in children with mild and severe malaria.

Glycosylphosphatidylinositol (GPI) glycolipids abound on the cell surface at the merozoite stage of Plasmodium falciparum life cycle are a central toxin in malaria. The contribution of GPI specific humoral immune responses to protection against malaria pathology is not clear, since studies on the correlation between anti-GPI antibody titers and disease severity have yielded contradictory results. Here, we present the application of a carbohydrate microarray based on synthetic PfGPI glycans to assess levels and fine specificities of anti-GPI antibody responses in healthy and malaria diseased individuals. Furthermore, the age dependent development of humoral immune responses against GPI in malaria-exposed children was investigated. Anti-GPI antibodies were only rarely found in children under the age of 18 months. Sera from subjects with severe malaria and healthy children contained antibodies that recognized predominantly synthetic Man(3)-GPI and Man(4)-GPIs. In contrast, antibodies in sera of children with mild malaria also showed substantial reactivity with truncated glycans comprising glucosamine-inositol moieties without mannose or with only one or two mannose residues.

Efficient solid-phase synthesis of a series of cyclic and linear peptoid-dexamethasone conjugates for the cell permeability studies.

Cyclic peptides and their cyclic analogs have received a great deal of attention because of their numerous interesting biological activities and their challenging chemical synthesis. It has also been hypothesized that they might improve the cell permeability compared to linear molecules by providing internal hydrogen bonding and generally decreasing the conformational flexibility. In this study, a series of cyclic and linear peptoid-dexamethasone conjugates were rationally designed and efficiently synthesized on solid-phase for systematic cell permeability studies using reporter gene-based assays. These model compounds should be used to reveal how the cell permeability of cyclic molecules is affected by several physicochemical properties, especially, the reduced conformational flexibility and the ring size. In addition, the synthetic strategy that was adopted in this study can also provide a robust platform for postchemical modifications of various molecular scaffolds in solid-phase or solution-phase syntheses.

Factors Affecting Quality of Life and Satisfaction in Patients with Arthritis after Change to a Fixed-Dose Naproxen/Esomeprazole Combination Drug.

BACKGROUND: In drug therapy for patients with arthritis, a naproxen/esomeprazole combination drug may be a tolerable choice because it can minimize gastrointestinal and cardiovascular adverse effects. The aim of this study was to investigate the changes in quality of life (QOL), medication adherence, and satisfaction after switch from the existing drug to the combination drug. In addition, we analyzed the correlation between the above-mentioned variables and the stratified demographic and medical data of the patients. METHODS: A prospective, noninterventional, observational study was conducted in 30 hospitals between May 2014 and July 2016. In total, 2,308 patients with osteoarthritis, 99 patients with rheumatoid arthritis, and 76 patients with ankylosing spondylitis were enrolled. Demographic information (age, sex, body mass index [BMI], alcohol consumption, and smoking) and medical information (type of arthritis, duration of disease, and comorbidities) were collected via a self-administered questionnaire. Patients were observed for more than three months after switching to the combination drug. Data on the QOL (EuroQoL 5-Dimension questionnaire [EQ-5D questionnaire]), medication adherence (Morisky Medication Adherence Scale [MMAS]), and satisfaction were collected at the first and last visits. RESULTS: A total of 2,483 patients enrolled at 30 hospitals completed the questionnaire. After the switch to the combination drug, the mean EQ-5D score improved from 0.72 ± 0.17 to 0.79 ± 0.14 (p < 0.001), and significant improvement was associated with female sex (p = 0.016), shorter disease duration (p < 0.001), and absence of comorbidities (p < 0.001). The mean MMAS score was 6.38 ± 1.77, indicating medium adherence. Satisfaction was significantly higher in female patients (p < 0.001), in patients with a shorter disease duration (p < 0.001), osteoarthritis (p = 0.003), and no comorbidities (p < 0.001). Serious drug-related adverse effects did not occur. CONCLUSIONS: The overall QOL was improved with medium adherence after the switch to the combination drug. On the basis of the analysis of stratified data, sex, age, drinking, smoking, disease duration, comorbidities, and BMI might be associated with QOL, satisfaction, and adherence.

Predictors of the need for laminectomy after indirect decompression via initial anterior or lateral lumbar interbody fusion.

OBJECTIVE: The goal of this study was to evaluate factors that are associated with the need for additional posterior direct decompressive surgery after anterior lumbar interbody fusion (ALIF) or lateral lumbar interbody fusion (LLIF). METHODS: Eighty-six adult patients who underwent ALIF or LLIF for degenerative spondylolisthesis and foraminal stenosis were enrolled. Patient factors (age, sex, number of surgery levels, and visual analog scale [VAS] score for leg and back pain); procedure-related factors (cage height and lordosis); and radiographic measurements (disc height [DH]; foraminal height [FH], foraminal area [FA], central canal diameter [CCD], and facet joint degeneration [FD]) were analyzed. All patients underwent staged surgery on 2 different days, with the anterior portion first, followed by the posterior portion. RESULTS: Of 86 patients, 62 underwent posterior decompression and 24 had no posterior decompression. There were no significant differences between groups with regard to age, sex, preoperative VAS score for back pain, cage height, cage angulation, preoperative DH, FH, FA, CCD, and FD (p > 0.05). The group that underwent posterior decompression showed statistically different numbers of treated segments (1.92 vs 1.21, p < 0.01), preoperative VAS leg score (7.9 vs 6.3), symptom duration (14.2 months vs 9.4 months), postoperative DH improvement (61.3% vs 96.2%), postoperative FH improvement (21.5% vs 32.1%), postoperative FA improvement (24.1% vs 36.9%), and cage height minus preoperative DH (5.3 mm vs 7.5 mm) compared with the nondecompression group. CONCLUSIONS: There appears to be some correlation between the need for posterior decompression and the number of treated segments, VAS leg scores, symptom duration, FH, FA, and difference between the cage height and preoperative DH. In selected patients undergoing staged surgery, indirect decompression without direct decompression may be a reasonable option in treating degenerative spinal conditions.