Miracle-dz/UniFAR-FTUs huggingface dataset:
Ibuprofen‐loaded poly(trimethylene carbonate‐co‐ε‐caprolactone) electrospun fibres for nerve regeneration

The development of scaffolds that combine the delivery of drugs with the physical support provided by electrospun fibres holds great potential in the field of nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well‐known non‐steroidal anti‐inflammatory drug, in electrospun fibres of the statistical copolymer poly(trimethylene carbonate‐co‐ε‐caprolactone) [P(TMC‐CL)] to serve as a drug delivery system to enhance axonal regeneration in the context of a spinal cord lesion, by limiting the inflammatory response. P(TMC‐CL) fibres were electrospun from mixtures of dichloromethane (DCM) and dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology, as well as mean fibre diameter, which decreased as the DMF content in solution increased. Ibuprofen‐loaded fibres were prepared from P(TMC‐CL) solutions containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to jet instability, resulting in the formation of a less homogeneous fibrous mesh. Under the optimized conditions, drug‐loading efficiency was above 80%. Confocal Raman mapping showed no preferential distribution of ibuprofen in P(TMC‐CL) fibres. Under physiological conditions ibuprofen was released in 24 h. The release process being diffusion‐dependent for fibres prepared from DCM solutions, in contrast to fibres prepared from DCM–DMF mixtures where burst release occurred. The biological activity of the drug released was demonstrated using human‐derived macrophages. The release of prostaglandin E2 to the cell culture medium was reduced when cells were incubated with ibuprofen‐loaded P(TMC‐CL) fibres, confirming the biological significance of the drug delivery strategy presented. Overall, this study constitutes an important contribution to the design of a P(TMC‐CL)‐based nerve conduit with anti‐inflammatory properties. Copyright © 2013 John Wiley & Sons, Ltd.
Long-term Outcomes of Postoperative Septic Arthritis After Anterior Cruciate Ligament Reconstruction

Background: Septic arthritis is a rare but potentially devastating complication of anterior cruciate ligament (ACL) reconstruction surgery. Several studies, including one by this group, have reported short- and medium-term outcomes, but to our knowledge there are no long-term follow-up studies. Hypothesis: Postoperative septic arthritis after ACL reconstruction surgery will lead to diminished long-term outcomes compared with surgery without infectious complications, likely related to the development of arthritis. Study Design: Case series; Level of evidence, 4. Methods: Four of 831 consecutive patients undergoing arthroscopically guided ACL reconstruction surgeries performed by 1 surgeon were previously reported on by this group at an average follow-up of 36 months. These same patients were contacted and reevaluated. Each patient underwent a physical examination, functional testing, and subjective evaluations with the SF-36, Lysholm, International Knee Documentation Committee (IKDC), and Tegner activity scale scores. Plain film radiographs and magnetic resonance imaging (MRI) scans were analyzed by 2 musculoskeletal radiologists. Results: Average follow-up time for this study was 17.9 years, and average age was 44.3 years. No other injuries or surgeries had occurred from the time of the previous study. Each patient had a decline in SF-36, Lysholm, and IKDC score, and the average Tegner score was unchanged. Average vertical hop test performance and Biodex dynamometry were both improved. The average side-to-side displacement measured via the KT-1000 arthrometer was increased. Radiographic and MRI studies revealed progression of arthritis in all patients and ACL graft rupture in 1 patient. Conclusion: Patients who develop septic arthritis as a complication of ACL reconstruction surgery have diminished long-term subjective, functional, and radiographic outcomes compared with historical reports of uncomplicated cases, likely related to pain from advanced arthritis. As compared with their own earlier follow-up, these patients had declines in pain-related subjective measures but remained stable or improved in both functional testing and activity-related subjective scales.
The Calcium Store Sensor, STIM1, Reciprocally Controls Orai and CaV1.2 Channels

Channel STIMulation The STIM1 protein functions as a calcium sensor and regulates entry of calcium into cells across the plasma membrane. When cell surface receptors are stimulated and cause release of calcium from internal stores in the endoplasmic reticulum (ER), STIM proteins in the ER membrane interact with the Orai channel pore protein in the plasma membrane to allow calcium entry from the outside of the cell (see the Perspective by Cahalan). Park et al. (p. 101) and Wang et al. (p. 105) now show that STIM also acts to suppress conductance by another calcium channel—the voltage-operated CaV1.2 channel. STIM1 appeared to interact directly with CaV1.2 channels in multiple cell types, including vascular smooth muscle cells, neurons, and cultured cells derived from T lymphocytes. The interaction inhibited opening of the CaV1.2 channels and caused depletion of the channel from the cell surface. The sensor protein that monitors depletion of intracellular calcium regulates two classes of calcium entry channels. Calcium signals, pivotal in controlling cell function, can be generated by calcium entry channels activated by plasma membrane depolarization or depletion of internal calcium stores. We reveal a regulatory link between these two channel subtypes mediated by the ubiquitous calcium-sensing STIM proteins. STIM1 activation by store depletion or mutational modification strongly suppresses voltage-operated calcium (CaV1.2) channels while activating store-operated Orai channels. Both actions are mediated by the short STIM-Orai activating region (SOAR) of STIM1. STIM1 interacts with CaV1.2 channels and localizes within discrete endoplasmic reticulum/plasma membrane junctions containing both CaV1.2 and Orai1 channels. Hence, STIM1 interacts with and reciprocally controls two major calcium channels hitherto thought to operate independently. Such coordinated control of the widely expressed CaV1.2 and Orai channels has major implications for Ca2+ signal generation in excitable and nonexcitable cells.
The Effect of Musculoskeletal Pain on Health-Related Quality of Life and Exercise Capacity

Abstract Objectives: To compare health-related quality of life [QOL] and exercise capacity of the individuals with mild pain not requiring medical advice and not related to any musculoskeletal disease or problem with that of no pain individuals. Methods: Fifty-two healthy individuals without a musculoskeletal system disease were enrolled to the study. Demographic data and medical statuses were recorded. Pain severity by visual analog scale and quality of life by the World Health Organization Quality of Life [WHOQOL BREF-27] assessment were evaluated. The six-minute walking test was used to measure the exercise capacity. Peripheral oxygen saturation, heart rate, leg fatigue and dyspnea were recorded before and after the six-minute walking test. Results: Forty-three percent of the participants [Group 1] had mean pain severity according to the visual analog scale 40.54 ± 2.03, while 56.7% [Group 2] did not have pain. In Group 1, the scores of the physical health, psychological health and social relationships domains of the WHOQOL BREF questionnaire were lower than Group 2 and the difference was statistically significant. While walking distance was similar in both groups, changes before and after the exercise test, dyspnea severity and perceived leg fatigue were found significantly higher in the Group 1 [p < 0.05]. A significant correlation was found between all subgroups of WHOQOL BREF and walking distance [p < 0.05]. Conclusions: Participants reporting mild pain severity have negatively impaired QOL in physical health, psychological health and social relationships, perceived dyspnea severity and leg fatigue during exercise compared with persons without pain. Additionally, QOL impairment was found in relation with pain severity and exercise capacity.
Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis

Form and Function The Planar Cell Polarity (PCP) signaling pathway governs cell movements that drive axis elongation and neural tube closure in vertebrate embryos, and certain vertebrate PCP proteins have also been implicated in ciliogenesis. Likewise, the septin cytoskeleton controls diverse cell behaviors, such as cytokinesis and cell migration, but little is known about how septin functions are regulated in vivo. Kim et al. (p. 1337, published online 29 July; see the Perspective by Barral) found that control of septins by the PCP effector protein, Fritz, was a crucial control point for morphogenesis and ciliogenesis. During neural tube closure, Fritz-mediated septin localization maintained cell shape but not cell polarity. In ciliated epithelial cells, Fritz was required for assembly of the septin rings at the base of cilia, which are needed for normal ciliogenesis and signaling. A gene involved in morphogenesis and ciliogenesis is mutated in patients with Bardet-Biedl syndrome. The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease.
A Matched-Cohort Population Study of Reoperation After Meniscal Repair With and Without Concomitant Anterior Cruciate Ligament Reconstruction

Background: Evidence for the success of a meniscal repair performed alone versus combined with anterior cruciate ligament reconstruction (ACLR) is equivocal. No large-scale comparative studies exist regarding this issue. Hypothesis: In the general population, meniscal repair in a presumed stable knee has the same rate of reoperation as meniscal repair performed with ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: All meniscal repairs performed with ACLR in Ontario, Canada, between July 2003 and March 2008 in patients aged 15 to 60 years were identified using administrative billing, diagnostics, and procedural coding. This cohort was matched 1:1 for sex, age, and calendar year of surgery with a cohort of patients who underwent meniscal repair alone. The McNemar test of matched pairs was used to compare reoperation rates (debridement or repair) within 2 years of the index procedure. Conditional logistic regression analysis was used to identify potential risk factors for reoperation among unmatched patient (socioeconomic status surrogate, comorbidity) and provider (surgeon volume, academic hospital status) factors. Results: Of 1332 patients who underwent meniscal repair and ACLR, 1239 (93%) were matched with patients who underwent meniscal repair alone. The rate of meniscal reoperation was 9.7% in the combined cohort compared with 16.7% in the repair alone cohort (P < .0001). In the regression analysis, only ACLR was protective against meniscal reoperation (odds ratio, 0.57; P < .0001). Surgeon volume of meniscal repair did not influence outcome. Conclusion: A meniscal repair performed in conjunction with ACLR carries a 7% absolute and 42% relative risk reduction of reoperation after 2 years compared with isolated meniscal repair.
Comparison of Drop Jumps and Sport-Specific Sidestep Cutting

Background: Anterior cruciate ligament (ACL) injuries are a serious problem, with a high incidence and serious consequences. Published clinical screening tests are based on 2-legged and controlled drop jumps, but ACL injuries are known to occur in single-legged landings and sidestep cutting, where the load is predominantly distributed to a single leg. Purpose: To describe knee kinematics and kinetics in drop jumps and sidestep cutting and investigate the rank correlation of knee valgus angles and knee abduction moments between and within these movements. Study Design: Controlled laboratory study. Methods: A total of 120 elite female handball players (mean ± SD: age, 22.4 ± 7.1 years; height, 171 ± 7 cm; weight, 67 ± 7 kg), each performed 3 drop jumps and 3 sport-specific sidestep cuts to each side. Kinematics and kinetics were calculated from high-speed 3-dimensional motion analysis. Results: Knee kinematics and kinetics were significantly different between drop jumps and sidestep cutting. The knee abduction moment was 6 times higher in sidestep cutting (1.58 ± 0.60 Nm/kg vs 0.25 ± 0.16 Nm/kg). There was a poor correlation between knee abduction moments (ρ = 0.135) in the 2 tasks, but a moderate correlation (ρ = 0.706) for knee valgus angles. There was a poor correlation between knee valgus angles in drop jumps and knee abduction moments in sidestep cuts (ρ = 0.238). Conclusion: Motion patterns are different between drop jumps and sidestep cutting. There is a moderate correlation for knee abduction moments between the 2 tasks, but knee abduction moments are less consistent across tasks. Clinical Relevance: Knee valgus angles during drop jumps do not predict knee abduction moments during sidestep cutting. The moderate correlation of knee valgus angles in drop jumps and sidestep cutting indicates that this measure may be more relevant for screening efforts.
Augmented Feedback Supports Skill Transfer and Reduces High-Risk Injury Landing Mechanics

Background: There is a current need to produce a simple, yet effective method for screening and targeting possible deficiencies related to increased anterior cruciate ligament (ACL) injury risk. Hypothesis: Frontal plane knee angle (FPKA) during a drop vertical jump will decrease upon implementing augmented feedback into a standardized sport training program. Study Design: Controlled laboratory study. Methods: Thirty-seven female participants (mean ± SD: age, 14.7 ± 1.5 years; height, 160.9 ± 6.8 cm; weight, 54.5 ± 7.2 kg) were trained over 8 weeks. During each session, each participant received standardized training consisting of strength training, plyometrics, and conditioning. They were also videotaped running on a treadmill at a standardized speed and performing a repeated tuck jump for 10 seconds. Study participants were randomized into 2 groups and received augmented feedback on either their jumping (AF) or sprinting (CTRL) form. Average (mean of 3 trials) and most extreme (trial with greatest knee abduction) FPKA were calculated from 2-dimensional video captured during performance of the drop vertical jump. Results: After testing, a main effect of time was noted, with the AF group reducing their FPKA average by 37.9% over the 3 trials while the CTRL group demonstrated a 26.7% reduction average across the 3 trials (P < .05). Conversely, in the most extreme drop vertical jump trial, a significant time-by-group interaction was noted (P < .05). The AF group reduced their most extreme FPKA by 6.9° (pretest, 18.4° ± 12.3°; posttest, 11.4° ± 10.1°) on their right leg and 6.5° (pretest, 16.3° ± 14.5°; posttest, 9.8° ± 10.7°) on their left leg, which represented a 37.7% and 40.1% reduction in FPKA, respectively. In the CTRL group, no similar changes were noted in the right (pretest, 16.9° ± 14.3°; posttest, 14.0° ± 12.3°) or left leg (pretest, 9.8° ± 11.1°; posttest, 7.2° ± 9.2°) after training. Conclusion: Providing athletes with augmented feedback on deficits identified by the tuck jump assessment has a positive effect on their biomechanics during a different drop vertical jump task that is related to increased ACL injury risk. The ability of the augmented feedback to support the transfer of skills and injury risk factor reductions across different tasks provides exciting new evidence related to how neuromuscular training may ultimately cross over into retained biomechanics that reduce ACL injuries during sport. Clinical Relevance: The tuck jump assessment’s ease of use makes it a timely and economically favorable method to support ACL prevention strategies in young girls.
Arthroscopically Assisted 2-Bundle Anatomic Reduction of Acute Acromioclavicular Joint Separations

Background: Currently, no clinical midterm results have been reported on arthroscopically assisted reduction of the acutely dislocated acromioclavicular (AC) joint using suture-button devices for fixation. Hypothesis: Athroscopically assisted reduction of the acutely dislocated AC joint yields satisfactory clinical outcomes without loss of reduction, clavicle migration, or AC joint degeneration at midterm follow-up evaluation. Study Design: Case series; Level of evidence, 4. Methods: The clinical and radiographic outcomes of 23 of 30 consecutive patients (21 men, 2 women) who underwent anatomic reduction for acute AC joint dislocation using 2 suture-button devices between 2006 and 2007 were reviewed. Radiographic evaluation was performed by measurement of coracoclavicular (CC) distance and AC displacement. Clinical evaluation included a visual analog scale (VAS) for pain, the Constant score, the simple shoulder test, and the Short Form–36. Previously, this same patient collective was reviewed after 2 years of follow-up using similar methods. Results: All 23 patients were available for midterm follow-up examination 58 months postoperatively. There were 3 Rockwood type III, 3 type IV, and 17 type V acromioclavicular joint separations. Mean ± SD follow-up was 58 ± 5.6 months (range, 51-67 months). Most patients (96%) remained very satisfied or satisfied with the procedure outcome. The VAS and Constant score improved significantly when compared with baseline (0.3 ± 0.6 and 91.5 ± 4.7 at 58 months postoperatively vs 4.5 ± 1.9 and 34.5 ± 6.9 at baseline) and remained essentially unchanged when compared with the 2-year outcome scores (0.3 ± 0.6 and 91.5 ± 4.7 at 58 months postoperatively vs 0.25 ± 0.5 and 94.3 ± 3.2 at 2 years). Radiographs showed 8 radiographic failures (undercorrection, posterior displacement, or both) and 4 additional overcorrections of the CC distance. When comparing with 24-month data, 17 of 20 radiographs remained unchanged; 1 case of previous overcorrection drifted into normal AC alignment and 2 cases increased in posterior subluxation of the clavicle. Conclusion: Arthroscopically assisted reduction of the acutely dislocated AC joint provides satisfactory clinical results 58 months after surgery. Compared with the baseline, all patients improved significantly. Two of 23 patients revealed an increased posterior dislocation compared with evaluation 24 months after surgery. No further migration of the clavicle or AC joint degeneration was observed.
Low‐sodium haemodialysis without fluid removal improves blood pressure control in chronic haemodialysis patients

SUMMARY: Hypertension is an important and well‐established risk factor for both cardiovascular and cerebrovascular disease. Hypertension is much more common in patients on renal replacement therapy than in the general population. Up to 80% of patients on renal replacement therapy are hypertensive and about 50% of dialysis patients die from cardiovascular causes. Salt and water overload are major factors exacerbating hypertension in the dialysis population. This was a prospective crossover study of 10 patients examining the effect of haemodialysis for 2 weeks using usual (Na+ 138–140 mmol/L) sodium dialysate with a 2‐week period of low (reduced by an average of 5 mmol/L Na+ to 133 mmol/L on average) sodium dialysate on inter‐dialytic ambulatory blood pressure (ABPM) and trans‐thoracic bioimpedance (TTB). Ten patients, mean age 67 years, completed the study (two women and eight men). No patient became severely hyponatraemic during the study period. Mean 48 h inter‐dialytic blood pressure (BP) fell from 141/83 to 133/78 (P < 0.01). Mean arterial BP measured immediately prior to TTB fell from 92.8 mmHg to 87.5 mmHg (P < 0.01) during the low‐sodium haemodialysis period. Afterload (systemic vascular resistive index – SVRI) measured by TTB fell significantly during the low‐sodium haemodialysis period (SVRI on Na+‐140 = 3426 cf. Na+‐134 = 2281; P = 0.01). Dialysate sodium reduction without extra fluid removal had a beneficial effect on inter‐dialytic 48‐h blood pressure in chronic stable haemodialysis patients. Lowering dialysate sodium reduced the systemic vascular resistance index as measured by TTB. Reduction of dialysate sodium was well tolerated, although mild dizzines and cramps did occur. These data suggest that sodium overload and water overload may have independent effects on BP and that simple‐to‐achieve and modest changes in dialysate sodium could usefully augment the action of antihypertensives in dialysis patients.
Differential Arginylation of Actin Isoforms Is Regulated by Coding Sequence–Dependent Degradation

Making Modifications Arginylation of β-actin regulates cell motility and the actin cytoskeleton, but how differential arginylation of the two highly similar actin isoforms—β and γ—is achieved in vivo is unclear. Zhang et al. (p. 1534; see the Perspective by Weygand-Durasevic and Ibba) describe a cotranslational mechanism that selectively regulates the arginylation of proteins through degradation and is dependent on the nucleotide coding sequence coupled to the translation speed. The work provides an explanation for the different N-terminal arginylation states of β- and γ-actin in vivo and suggests translation rate affected by nucleotide coding sequence confers different posttranslational states to proteins and selectively regulates protein degradation. The translational speed of proteins influences whether they are cotranslationally degraded after arginylation. The mammalian cytoskeletal proteins β- and γ-actin are highly homologous, but only β-actin is amino-terminally arginylated in vivo, which regulates its function. We examined the metabolic fate of exogenously expressed arginylated and nonarginylated actin isoforms. Arginylated γ-actin, unlike β-, was highly unstable and was selectively ubiquitinated and degraded in vivo. This instability was regulated by the differences in the nucleotide coding sequence between the two actin isoforms, which conferred different translation rates. γ-actin was translated more slowly than β-actin, and this slower processing resulted in the exposure of a normally hidden lysine residue for ubiquitination, leading to the preferential degradation of γ-actin upon arginylation. This degradation mechanism, coupled to nucleotide coding sequence, may regulate protein arginylation in vivo.