Optimisation of the preservation conditions for molecularly imprinted polymer nanoparticles specific for trypsin.

The influence of lyophilisation, autoclaving and sonication on the stability and performance of trypsin-specific molecularly imprinted polymer nanoparticles (MIP NPs) has been studied in order to improve their long-term physical stability. Glucose, glycine, sorbitol and trehalose were tested as cryoprotectant agents during the lyophilisation treatment. The effect of lyophilisation and sterilisation on affinity of trypsin-specific NPs was assessed using Biacore 3000 instrument. The results have demonstrated that MIP NPs successfully withstood the lyophilisation and autoclaving conditions without a reduction of their recognition properties and affinity. It is possible to conclude that both tested lyophilisation and sterilisation treatments were suitable for a long-term storage of the prepared MIP NPs and could be used to store MIP NPs in dry state and hence reduce the chance of the bacterial contamination. An effective preservation of the MIP NPs is a crucial requirement for their future applications in the clinical diagnostics and bioimaging.

Formalizing Visualization Design Knowledge as Constraints: Actionable and Extensible Models in Draco.

There exists a gap between visualization design guidelines and their application in visualization tools. While empirical studies can provide design guidance, we lack a formal framework for representing design knowledge, integrating results across studies, and applying this knowledge in automated design tools that promote effective encodings and facilitate visual exploration. We propose modeling visualization design knowledge as a collection of constraints, in conjunction with a method to learn weights for soft constraints from experimental data. Using constraints, we can take theoretical design knowledge and express it in a concrete, extensible, and testable form: the resulting models can recommend visualization designs and can easily be augmented with additional constraints or updated weights. We implement our approach in Draco, a constraint-based system based on Answer Set Programming (ASP). We demonstrate how to construct increasingly sophisticated automated visualization design systems, including systems based on weights learned directly from the results of graphical perception experiments.

Ulnar neuropathy and medial elbow pain in women's fastpitch softball pitchers: a report of 6 cases.

BACKGROUND: Elite-level women's fastpitch softball players place substantial biomechanical strains on the elbow that can result in medial elbow pain and ulnar neuropathic symptoms. There is scant literature reporting the expected outcomes of the treatment of these injuries. This study examined the results of treatment in a series of these patients. METHODS: We identified 6 female softball pitchers (4 high school and 2 collegiate) with medial elbow pain and ulnar neuropathic symptoms. Trials of conservative care failed in all 6, and they underwent surgical treatment with subcutaneous ulnar nerve transposition. These patients were subsequently monitored postoperatively to determine outcome. RESULTS: All 6 female pitchers had early resolution of elbow pain and neuropathic symptoms after surgical treatment. Long-term follow-up demonstrated that 1 patient quit playing softball because of other injuries but no longer reported elbow pain or paresthesias. One player was able to return to pitching at the high school level but had recurrent forearm pain and neuritis 1 year later while playing a different sport and subsequently stopped playing competitive sports. Four patients continued to play at the collegiate level without further symptoms. CONCLUSIONS: Medial elbow pain in women's softball pitchers caused by ulnar neuropathy can be treated effectively with subcutaneous ulnar nerve transposition if nonsurgical options fail. Further study is necessary to examine the role of overuse, proper training techniques, and whether pitching limits may be necessary to avoid these injuries.

2,4-dichlorophenoxyacetic acid (2,4-D) and risk of non-Hodgkin lymphoma: a meta-analysis accounting for exposure levels.

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most commonly used selective herbicides in the world. A number of epidemiology studies have found an association between 2,4-D exposure and non-Hodgkin lymphoma (NHL) but these results are inconsistent and controversial. A previous meta-analysis found no clear association overall but did not specifically examine high-exposure groups. We conducted a systematic review and meta-analysis of the peer-reviewed epidemiologic studies of the associations between 2,4-D and NHL, with a particular focus on high-exposure groups, and evaluations of heterogeneity, dose-response, and bias. A total of 12 observational studies, 11 case-control studies, and one cohort study, were included. The summary relative risk for NHL using study results comparing subjects who were ever versus never exposed to 2,4-D was 1.38 (95% confidence interval (CI), 1.07-1.77). However, in analyses focusing on results from highly exposed groups, the summary relative risk for NHL was 1.73 (95% CI, 1.10-2.72). No clear bias based on study design, exposure assessment methodology, or outcome misclassification was seen. Overall, these findings provide new evidence for an association between NHL and exposure to the herbicide 2,4-D.

Cobalt-iron (oxy)hydroxide oxygen evolution electrocatalysts: the role of structure and composition on activity, stability, and mechanism.

Cobalt oxides and (oxy)hydroxides have been widely studied as electrocatalysts for the oxygen evolution reaction (OER). For related Ni-based materials, the addition of Fe dramatically enhances OER activity. The role of Fe in Co-based materials is not well-documented. We show that the intrinsic OER activity of Co(1-x)Fe(x)(OOH) is ∼100-fold higher for x ≈ 0.6-0.7 than for x = 0 on a per-metal turnover frequency basis. Fe-free CoOOH absorbs Fe from electrolyte impurities if the electrolyte is not rigorously purified. Fe incorporation and increased activity correlate with an anodic shift in the nominally Co(2+/3+) redox wave, indicating strong electronic interactions between the two elements and likely substitutional doping of Fe for Co. In situ electrical measurements show that Co(1-x)Fe(x)(OOH) is conductive under OER conditions (∼0.7-4 mS cm(-1) at ∼300 mV overpotential), but that FeOOH is an insulator with measurable conductivity (2.2 × 10(-2) mS cm(-1)) only at high overpotentials >400 mV. The apparent OER activity of FeOOH is thus limited by low conductivity. Microbalance measurements show that films with x ≥ 0.54 (i.e., Fe-rich) dissolve in 1 M KOH electrolyte under OER conditions. For x < 0.54, the films appear chemically stable, but the OER activity decreases by 16-62% over 2 h, likely due to conversion into denser, oxide-like phases. We thus hypothesize that Fe is the most-active site in the catalyst, while CoOOH primarily provides a conductive, high-surface area, chemically stabilizing host. These results are important as Fe-containing Co- and Ni-(oxy)hydroxides are the fastest OER catalysts known.

Contributions to activity enhancement via Fe incorporation in Ni-(oxy)hydroxide/borate catalysts for near-neutral pH oxygen evolution.

Ni-borate materials are oxygen evolution catalysts that operate at near-neutral pH and have been found previously to improve due to structural changes induced via anodic conditioning. We find that this increased activity after conditioning at 0.856 V vs. SCE, as measured on a turn-over frequency basis (TOF) at 400 mV overpotential (TOF = 0.38 s(-1)), accompanies significant Fe incorporation (14%). Films conditioned in Fe-free electrolyte exhibit ∼10 times lower activity (TOF = 0.03 s(-1)). By co-depositing Fe-Ni we demonstrate high activity without conditioning (TOF = 0.24 s(-1)) which improves further with shortened (∼30 min) conditioning (TOF = 1.4 s(-1)).

RuleBender: integrated modeling, simulation and visualization for rule-based intracellular biochemistry.

BACKGROUND: Rule-based modeling (RBM) is a powerful and increasingly popular approach to modeling cell signaling networks. However, novel visual tools are needed in order to make RBM accessible to a broad range of users, to make specification of models less error prone, and to improve workflows. RESULTS: We introduce RuleBender, a novel visualization system for the integrated visualization, modeling and simulation of rule-based intracellular biochemistry. We present the user requirements, visual paradigms, algorithms and design decisions behind RuleBender, with emphasis on visual global/local model exploration and integrated execution of simulations. The support of RBM creation, debugging, and interactive visualization expedites the RBM learning process and reduces model construction time; while built-in model simulation and results with multiple linked views streamline the execution and analysis of newly created models and generated networks. CONCLUSION: RuleBender has been adopted as both an educational and a research tool and is available as a free open source tool at http://www.rulebender.org. A development cycle that includes close interaction with expert users allows RuleBender to better serve the needs of the systems biology community.

[4-(Bromo-methyl)-benz-yl]triphenyl-phospho-nium bromide acetonitrile monosolvate.

In the title compound, C(26)H(23)BrP(+)·Br(-)·C(2)H(3)N, the dihedral angles between the plane of the benzylic phenyl ring attached to the P atom and the planes of the three directly attached phenyl rings are 34.04 (12), 45.48 (13) and 87.18 (9)°. In the crystal, centrosymmetric pairs of cations and anions are linked into dimeric aggregates via C-H⋯Br hydrogen bonds. There is also a C-H⋯N hydrogen bond to the acetonitrile solvent mol-ecule.

RuleBender: a visual interface for rule-based modeling.

SUMMARY: Rule-based modeling (RBM) is a powerful and increasingly popular approach to modeling intracellular biochemistry. Current interfaces for RBM are predominantly text-based and command-line driven. Better visual tools are needed to make RBM accessible to a broad range of users, to make specification of models less error prone and to improve workflows. We present RULEBENDER, an open-source visual interface that facilitates interactive debugging, simulation and analysis of RBMs. AVAILABILITY: RULEBENDER is freely available for Mac, Windows and Linux at http://rulebender.org.

Low profile fixation of radial head and neck fractures: surgical technique and clinical experience.

Radial head preservation with internal fixation is the preferred treatment for displaced radial head and neck fractures. Although plate fixation has been used successfully, concerns remain about loss of forearm rotation. A technique of low-profile fixation using obliquely oriented screws from the radial head into the shaft has been developed to avoid distal dissection of the soft tissues and placement of hardware in an already-constrained area adjacent to the annular ligament and lateral ligamentous structures. This technique is most useful in axially stable fractures that have no or minimal shaft comminution and is our preferred method of treatment to avoid distal dissection and placement of hardware along the radial neck.

Patient perceptions of open and arthroscopic shoulder surgery.

PURPOSE: There has been a significant increase in surgeon as well as patient interest in arthroscopic treatment of shoulder pathology. We hypothesize that patients have a strong preference for arthroscopic shoulder surgery. Currently, there are no data in the literature reporting on how people perceive open versus arthroscopic shoulder surgery. METHODS: Prospectively, a total of 202 patients were administered a questionnaire at the offices of 2 fellowship-trained shoulder surgeons, 1 located at a tertiary referral center (center A) and 1 in private practice (center B). The questionnaire asked a series of questions about specific factors when choosing an orthopaedic surgeon and the preference for arthroscopic or open surgery. In addition, 7 short-term and long-term outcomes were listed, and the patient was asked to choose whether open or arthroscopic surgery would provide the best outcome or whether he or she felt that there was no difference. RESULTS: Among patients at center A, 88% would prefer arthroscopy if they were to have shoulder surgery, as would 96% of patients at center B. Among patients at center A, 14% would avoid shoulder surgery if the only option was open surgery, as would 25% at center B. The reputation of the surgeon and institution were the primary factors in choosing a surgeon. Recommendation of a former patient and years of surgeon experience were less important factors for patient selection of a shoulder surgeon. CONCLUSIONS: The study shows that the vast majority of patients perceive multiple advantages of arthroscopic shoulder surgery despite a lack of published data to support many of these assumptions, particularly with regard to expected functional outcome of arthroscopic versus open shoulder surgery. CLINICAL RELEVANCE: Shoulder surgeons should be aware of these perceptions when discussing treatment options with patients. A continued effort should be made to emphasize known scientific data when considering the relative risks and benefits of arthroscopic and open shoulder surgery.

Arthroscopic rotator cuff debridement in patients with rheumatoid arthritis.

There is little information available concerning the results of rotator cuff debridement in patients with rheumatoid arthritis (RA). We performed a review of 16 shoulders with underlying RA that underwent arthroscopic rotator cuff tear debridement; there were 10 full-thickness tears and 6 partial-thickness tears. Of the 10 patients with full-thickness rotator cuff tears, 8 had unsatisfactory results, whereas none of the patients with partial-thickness tears had unsatisfactory results. Pain was improved in 5 of 6 shoulders with partial-thickness cuff tears, whereas only 5 of 10 with full-thickness tears had an improvement with regard to pain. Motion did not improve in either group. Patients with RA who require operative intervention for pain relief because of rotator cuff tearing can be treated successfully with debridement alone. However, pain relief was less predictable with large or massive tears when compared with partial-thickness tears, and functional gains were not achieved in either group.

Early complications of operatively treated proximal humeral fractures.

Minimal information exists regarding early complications after operatively treated proximal humeral fractures. Of the 82 shoulders that had osteosynthesis, 42 had a (nonmedical) complication, with 21 requiring further surgery. Of 42 shoulders with complications, 12 were related to incomplete reduction, 16 had loss of anatomic fracture fixation, 9 had delayed healing, 3 had an infection, 1 had rotator cuff failure, and 1 had loose bodies. Fixed-angle plates had lower rates of initial malpositioning and resultant malunion. Of the 22 shoulders requiring hemiarthroplasty, 14 had an early complication. Of these, 7 had complications relating to implant insertion or tuberosity malreduction at the index operation and 7 had problems with tuberosity healing. The rate of complications after operative treatment of proximal humeral fractures is high. All efforts at fracture fragment fixation with osteosynthesis and hemiarthroplasty should be directed at obtaining anatomic fracture fixation that resists displacement.

Patient and physician-assessed shoulder function after arthroplasty.

BACKGROUND: We found no information in the literature regarding the relationship between patient and physician-derived outcome assessments with a shoulder questionnaire. In this study, we examined a group of patients who were assessed with patient and physician-administered questionnaires following shoulder arthroplasty. METHODS: From August 2003 to February 2004, sixty-seven consecutive patients who had been followed for a minimum of six months after shoulder arthroplasty were evaluated with a self-administered and an identical physician-directed shoulder questionnaire that assessed clinical and functional outcomes at the time of routine follow-up. An assessment of the agreement between physicians and patients as well as the factors that affected agreement was performed. RESULTS: The intraclass correlation indicated almost perfect physician-patient agreement (>0.80) on items related to overall pain, pain at night, pain with activity, stability, and active elevation and substantial agreement (intraclass correlation, 0.66 and 0.69) between the physician and patient assessments of pain without activity and strength. While the differences were small, on the average physician ratings for pain were lower (indicating less pain) than patient ratings for pain, physicians rated stability and strength as being closer to normal, and they reported less active elevation. There was substantial agreement between the physician and patient assessments of outcome with the modified Neer system (intraclass correlation = 0.75), with 87% agreement if excellent and satisfactory outcomes were combined. CONCLUSIONS: A patient-derived questionnaire can provide a high level of agreement with surgeon assessments of outcome following shoulder surgery. Patient-administered methods should continue to be evaluated as a means of assessment of these patients.

Arthroscopic shoulder synovectomy in patients with rheumatoid arthritis.

PURPOSE: Currently, there is little information available concerning the results of shoulder synovectomy in patients with rheumatoid arthritis. Furthermore, it remains difficult to assess the success of shoulder synovectomy because of a high association of rotator cuff tears in rheumatoid patients. We hypothesized that synovectomy in patients with a functionally intact rotator cuff would provide durable pain relief. TYPE OF STUDY: Case series. METHODS: Sixteen shoulders in 13 patients with rheumatoid arthritis were treated with arthroscopic shoulder synovectomy from 1988 to 2002 with a mean follow-up of 5.5 years. Patients with full-thickness rotator cuff tears or partial tears that required repair were excluded. Two of the 13 patients had been diagnosed with juvenile rheumatoid arthritis and 11 had adult-onset disease. The medical records of the patients were reviewed and patients were assessed clinically and by questionnaire to assess pain, satisfaction, range of motion, radiographic outcomes, and occurrence of complications. RESULTS: There was an improvement in pain at long-term follow-up in 13 of 16 patients (P < .001). Active shoulder elevation improved from a median of 145 degrees to 160 degrees but was not significant (P = .14). External rotation improved significantly (P = .01) from a median of 45 degrees (range, 0 degrees to 90 degrees) to 60 degrees (range, 0 degrees to 100 degrees). According to the Neer rating system, there were 5 excellent, 8 satisfactory, and 3 unsatisfactory results. Seven of 8 shoulders followed-up radiographically for more than 1 year showed radiographic progression of disease. All 3 patients reporting pain that was no better or worse than before surgery had radiographic arthrosis at last follow-up with advancing periarticular erosions and reduction of glenoid articular space. CONCLUSIONS: Arthroscopic synovectomy of the shoulder in patients with rheumatoid arthritis with an intact rotator cuff offers a reliable decrease in pain with less predictable improvements in range of motion. Limitations in predicting final results based on preoperative radiographs should be discussed with patients; those with more advanced radiographic changes may not benefit from the procedure. LEVEL OF EVIDENCE: Level IV, therapeutic study, case series, no control group.

Complications of operative fixation of proximal humeral fractures in patients with rheumatoid arthritis.

Currently, there is no information in the literature on operative treatment of proximal humeral fractures in patients with rheumatoid arthritis. Eleven patients underwent osteosynthesis of the proximal humerus from December 1987 to December 2002. Nine patients were treated for acute fractures, and two were treated for nonunions. Four had loss of initial anatomic reduction, two were treated nonoperatively with resultant malunion, and two required revision fixation. Two patients with symptomatic pseudarthrosis were treated with internal fixation and bone grafting. Both had complications (1 requiring hemiarthroplasty after painful nonunion and 1 with chondrolysis). All patients with acute fractures achieved fracture union. One patient had an excellent result, four had satisfactory results, and six had an unsatisfactory result. Patients and treating physicians should be aware of the high rate of complications and unsatisfactory results in patients with rheumatoid arthritis who undergo operative treatment of proximal humeral fractures.

Outcomes are poor after treatment of sepsis in the rheumatoid shoulder.

Currently, there is little information regarding treatment of shoulder sepsis in patients with rheumatoid arthritis. This study examines the prognosis and outcome after operative treatment of native shoulder infection in patients with rheumatoid arthritis. Seventeen patients were retrospectively reviewed (20 shoulders) after surgical intervention for shoulder sepsis between 1982 and 2002. Nine patients (12 shoulders) were associated with multiple joint infections. The most common isolated organism from cultures was Staphylococcus aureus in 15 shoulders. Three patients died during initial admission to the hospital (at 7 days, 5 months, and 6 months) because of multisystem organ failure and multiple joint infections. Fourteen patients (15 shoulders) survived for followup, with two excellent, six satisfactory, and seven unsatisfactory results. Mean active elevation was 100 degrees. Further surgery was required in three patients: one synovectomy and two shoulder arthrodeses. In this study, patients with shoulder sepsis with rheumatoid arthritis were found to have a high rate of multiple joint sepsis and unsatisfactory shoulder function.

Rotator cuff repair in patients with rheumatoid arthritis.

BACKGROUND: Currently, there is very little information available regarding the results of rotator cuff repair in patients with rheumatoid arthritis. Therefore, we reviewed our experience to determine the results, the risk factors for an unsatisfactory outcome, and the rates of failure of this procedure. METHODS: We retrospectively reviewed the records of all patients with rheumatoid arthritis who had undergone repair of a rotator cuff tear at our institution from 1988 to 2002. Twenty-three shoulders in twenty-one patients were identified. The median duration of follow-up for the twenty shoulders that did not require revision surgery was 9.7 years. Nine shoulders had a partial-thickness tear, and fourteen had a full-thickness tear. The shoulders were assessed with regard to pain, functional outcome, and overall patient satisfaction. RESULTS: Patients with both partial and full-thickness rotator cuff tears had significant improvements in terms of overall pain (p < 0.05) and satisfaction (p < 0.05). Patients who had undergone repair of a partial-thickness tear had improved active elevation (from 155 degrees to 180 degrees; p = 0.03), whereas patients who had undergone repair of a full-thickness tear did not have improved elevation. Six of the fourteen shoulders with a full-thickness tear had an unsatisfactory result, whereas only two of the nine shoulders with a partial-thickness tear had an unsatisfactory result. CONCLUSIONS: Rotator cuff repair in patients with rheumatoid arthritis can be challenging. However, durable pain relief and patient satisfaction can be achieved. Functional gains should not be expected in patients with full-thickness rotator cuff tears. Repair of the rotator cuff in patients with rheumatoid arthritis can be undertaken when nonoperative measures for pain relief have failed.

Vascular changes of the hand in professional baseball players with emphasis on digital ischemia in catchers.

BACKGROUND: Repetitive trauma to the hand is a concern for baseball players. The present study investigated the effects of repetitive trauma and the prevalence of microvascular pathological changes in the hands of minor league professional baseball players. In contrast to previous investigators, we documented the presence of abnormalities in younger, asymptomatic individuals. METHODS: Thirty-six baseball players on active minor league rosters underwent a history and physical examination of both hands as well as additional specialized tests, including Doppler ultrasound, a timed Allen test, determination of digital brachial pressure indices, and ring sizing of fingers. Data were compared between gloved hands and throwing hands, hitters and nonhitters, and players at four different positions (catcher [nine subjects], outfielder [seven subjects], infielder [five subjects], and pitcher [fifteen subjects]). RESULTS: Digital brachial indices in the ring fingers of the gloved (p < 0.05) and throwing hands (p < 0.02) of catchers were significantly diminished compared with those in all other players. Doppler testing showed a significantly greater prevalence of abnormal flow in the ulnar artery at Guyon's canal when catchers were compared with other position players (p < 0.01). Doppler abnormalities were significantly more common in the gloved hand compared with the throwing hand (p < 0.05). Seven of nine catchers (and only catchers) were found to have index finger hypertrophy (average change, two ring sizes; p < 0.01); the hypertrophy occurred at the proximal phalanx and the proximal interphalangeal joint of the gloved hand. Catchers had a significantly higher prevalence of subjective hand symptoms (specifically, weakness in the gloved hand) compared with pitchers and infielders/outfielders (44% compared with 7% and 17%, respectively; p < 0.05). CONCLUSIONS: Microvascular changes are present in the hands of otherwise healthy professional baseball players in all positions, with a significantly higher prevalence in catchers, prior to the development of clinically important ischemia. Repetitive trauma resulting from the impact of the baseball also leads to digital hypertrophy in the index finger of the gloved hand of catchers. Gloves currently used by professional catchers do not adequately protect the hand from repetitive trauma.

The "moving valgus stress test" for medial collateral ligament tears of the elbow.

BACKGROUND: The diagnosis of a painful partial tear of the medial collateral ligament in overhead-throwing athletes is challenging, even for experienced elbow surgeons and despite the use of sophisticated imaging techniques. HYPOTHESIS: The "moving valgus stress test" is an accurate physical examination technique for diagnosis of medial collateral ligament attenuation in the elbow. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Twenty-one patients underwent surgical intervention for medial elbow pain due to medial collateral ligament insufficiency or other abnormality of chronic valgus overload, and they were assessed preoperatively with an examination called the moving valgus stress test. To perform the moving valgus stress test, the examiner applies and maintains a constant moderate valgus torque to the fully flexed elbow and then quickly extends the elbow. The test is positive if the medial elbow pain is reproduced at the medial collateral ligament and is at maximum between 120 degrees and 70 degrees. RESULTS: The moving valgus stress test was highly sensitive (100%, 17 of 17 patients) and specific (75%, 3 of 4 patients) when compared to assessment of the medial collateral ligament by surgical exploration or arthroscopic valgus stress testing. The mean shear range (ie, the arc within which pain was produced with the moving valgus stress test) was 120 degrees to 70 degrees. The mean angle at which pain was at a maximum was 90 degrees of elbow flexion. CONCLUSIONS: The moving valgus stress test is an accurate physical examination technique that, when performed and interpreted correctly, is highly sensitive for medial elbow pain arising from the medial collateral ligament.