Surface modification to improve in vitro attachment and proliferation of human urinary tract cells

To evaluate the attachment and proliferation of cultured human urinary tract cells to culture plates surface-modified by photochemical immobilization of extracellular matrix (ECM) proteins. MATERIALS AND METHODS Human uroepithelial (UEC) and smooth muscle (SMC) cells were harvested from ureter and expanded in culture; 24-well culture plates surface-modified by photochemical covalent immobilization of ECM proteins were then seeded with UEC or SMC. To characterize cellular attachment, cells were incubated on surface-modified plates for 30 and 90 min. For proliferation assays the cells were incubated for 3 12 days. Standard tissue culture plates with no surface modification and sham-modified plates served as controls. Differential attachment and proliferation on the various surfaces were assessed using analysis of variance with Fisher's posthoc test for multiple comparisons. RESULTS Attachment at 30 and 90 min of both UEC and SMC on plates surface-modified with ECM proteins was significantly greater than in control plates. Surface-modification with collagen resulted in significantly greater cellular attachment than with either laminin or fibronectin. UEC proliferation was also significantly greater than in control plates by surface-modification with collagen and fibronectin, but not with laminin. SMC proliferation was significantly better after surface modification than on sham- modified plates, but was no better than standard plates. CONCLUSIONS Covalent photochemical immobilization of ECM proteins to potential growth surfaces enhances the attachment of cultured UEC and SMC and the proliferation of UEC. This technique might be useful in modifying surface properties of synthetic polymer-based materials in a controlled and defined manner, giving them the capacity to promote and sustain the growth of urinary tract cells. This may lead to development of alternative methods of tissue engineering in the urinary tract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73750/1/j.1464-410X.2003.04418.x.pd

RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells.

The RAD54 family DNA translocases have several biochemical activities. One activity, demonstrated previously for the budding yeast translocases, is ATPase-dependent disruption of RAD51-dsDNA binding. This activity is thought to promote dissociation of RAD51 from heteroduplex DNA following strand exchange during homologous recombination. In addition, previous experiments in budding yeast have shown that the same activity of Rad54 removes Rad51 from undamaged sites on chromosomes; mutants lacking Rad54 accumulate nonrepair-associated complexes that can block growth and lead to chromosome loss. Here, we show that human RAD54 also promotes the dissociation of RAD51 from dsDNA and not ssDNA. We also show that translocase depletion in tumor cell lines leads to the accumulation of RAD51 on chromosomes, forming complexes that are not associated with markers of DNA damage. We further show that combined depletion of RAD54L and RAD54B and/or artificial induction of RAD51 overexpression blocks replication and promotes chromosome segregation defects. These results support a model in which RAD54L and RAD54B counteract genome-destabilizing effects of direct binding of RAD51 to dsDNA in human tumor cells. Thus, in addition to having genome-stabilizing DNA repair activity, human RAD51 has genome-destabilizing activity when expressed at high levels, as is the case in many human tumors

Performance of the PROMIS After Operative Interventions for Shoulder Instability

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to capture patient-reported outcomes (PROs) in an efficient manner. Few studies have assessed this instrument postoperatively. Purpose: To compare the PROMIS Physical Function computer adaptive test (PROMIS PF CAT) and Upper Extremity (PROMIS UE) item bank to other previously validated PRO instruments and to evaluate ceiling and floor effects and construct validity responsiveness in patients who underwent operative interventions for shoulder instability. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 72 patients who underwent operative interventions for shoulder instability completed the American Shoulder and Elbow Surgeons (ASES) assessment form, Marx shoulder activity scale (Marx), 36-Item Short Form Health Survey physical function (SF-36 PF) and general health (SF-36 GH), Western Ontario Shoulder Instability Index (WOSI), PROMIS PF CAT, and PROMIS UE before surgery and then at 6 weeks and 6 months postoperatively. Correlation coefficients were calculated among these tools. The effect size of change was also calculated for each tool at each time point. A total of 91 patients who had also undergone surgery for shoulder instability completed these PRO instruments 2 years postoperatively. The percentage of patients hitting the ceiling and floor effects of each of the PRO instruments was calculated at all time points. Results: The PROMIS PF CAT demonstrated excellent-good correlation with the SF-36 PF at all postoperative time points (0.61 at 6 weeks, 0.68 at 6 months, and 0.64 at 2 years; P \u3c .01 for all). The PROMIS UE showed excellent correlation with the ASES at 6 weeks postoperatively (0.73, P \u3c .01). Both the PROMIS PF CAT and PROMIS UE demonstrated the ability to detect change after surgical interventions with a medium to large effect size. The PROMIS UE demonstrated a ceiling effect at 6 months (68.1%) and 2 years (67.0%) postoperatively. The PROMIS PF CAT demonstrated no ceiling effect at any time point. Conclusion: The PROMIS PF CAT demonstrated good to excellent correlation with other previously validated PRO instruments that assess physical function in patients with shoulder instability postoperatively. The PROMIS UE demonstrated good correlation with other PRO tools but had a significant ceiling effect and is not recommended for this patient population. Both tools demonstrated an ability to detect change after surgical interventions with a good effect size

Performance of the PROMIS in Patients After Anterior Cruciate Ligament Reconstruction

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) is designed to advance patient-reported outcome (PRO) instruments by utilizing question banks for major health domains. Purpose: To compare the responsiveness and construct validity of the PROMIS physical function computer adaptive test (PF CAT) with current PRO instruments for patients before and up to 2 years after anterior cruciate ligament (ACL) reconstruction. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Initially, 157 patients completed the PROMIS PF CAT, Short Form-36 Health Survey (SF-36 physical function [PF] and general health [GH]), Marx Activity Rating Scale (MARS), Knee injury and Osteoarthritis Outcome Score (KOOS activities of daily living [ADL], sport, and quality of life [QOL]), and EuroQol-5 dimensions questionnaire (EQ-5D) at 6 weeks, 6 months, and 2 years after ACL reconstruction. Correlations between instruments, ceiling and floor effects, effect sizes (Cohen d), and standardized response means to describe responsiveness were evaluated. Subgroup analyses compared participants with and without additional arthroscopic procedures using linear mixed models. Results: At baseline, 6 weeks, and 6 months, the PROMIS PF CAT showed excellent or excellent-good correlations with the SF-36 PF (r = 0.75-0.80, P \u3c .01), KOOS-ADL (r = 0.63-0.70, P \u3c .01), and KOOS-sport (r = 0.32-0.69, P \u3c .01); excellent-good correlation with the EQ-5D (r = 0.60-0.71, P \u3c .01); and good correlation with the KOOS-QOL (r = 0.52-0.58, P \u3c .01). As expected, there were poor correlations with the MARS (r = 0.00-0.24, P \u3c .01) and SF-36 GH (r = 0.16-0.34, P \u3c .01 ). At 2 years, the PROMIS PF CAT showed good to excellent correlations with all PRO instruments (r = 0.42-0.72, P \u3c .01), including the MARS (r = 0.42, P \u3c .01), indicating frequent return to preinjury function. The PROMIS PF CAT had the fewest ceiling or floor effects of all instruments tested, and patients answered, on average, 4 questions. There was no significant difference in baseline physical function scores between subgroups; at follow-up, all groups showed improvements in scores that were not statistically different. Conclusion: The PROMIS PF CAT is a valid tool to assess outcomes after ACL reconstruction up to 2 years after surgery, demonstrating the highest responsiveness to change with the fewest ceiling and floor effects and a low time burden among all instruments tested. The PROMIS PF CAT is a beneficial alternative for assessing physical function in adults before and after ACL reconstruction

Performance of the PROMIS in Patients Undergoing 3 Common Elbow Procedures

Background: Ulnar collateral ligament (UCL) reconstruction, distal biceps tendon repair, and elbow arthroscopic surgery are common elbow procedures performed in active patients. Hypothesis: We hypothesized (1) good to excellent correlation between Patient-Reported Outcomes Measurement Information System (PROMIS) instruments and traditional orthopaedic upper extremity patient-reported outcome (PRO) measures; (2) that PROMIS instruments would demonstrate ceiling effects; and (3) that the PROMIS physical function computer adaptive test (PF CAT) would demonstrate a low question burden compared with other PRO instruments. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 76 patients undergoing UCL repair/reconstruction, distal biceps tendon repair, or elbow arthroscopic surgery filled out the Short Form–36 Health Survey (SF-36) Physical Function subscale, EuroQol–5 Dimensions (EQ-5D) questionnaire, PROMIS PF CAT, and PROMIS upper extremity item bank (UE). Excellent correlation between PROs was defined as ≥.70. Results: The PROMIS PF CAT had excellent correlation with the SF-36 (r = 0.74; P \u3c .0001), Disabilities of the Arm, Shoulder and Hand (DASH) survey (r = –0.76; P \u3c .0001), and PROMIS UE (r = 0.73; P \u3c .0001). The PROMIS UE demonstrated excellent correlation with the SF-36 (r = 0.73; P \u3c .0001) and DASH survey (r = –0.81; P \u3c .0001). The PROMIS UE had ceiling effects in 33% of patients. The SF-36 showed ceiling effects in 20% of patients. On average, patients answered 5.1 ± 2.2 questions on the PROMIS PF CAT. Conclusion: The PROMIS PF CAT and PROMIS UE are valid in patients undergoing distal biceps tendon repair, elbow arthroscopic surgery, and UCL repair. The PROMIS UE demonstrated high ceiling effects in younger, higher functioning patients and should be used with caution in this group. A further evaluation and modification of the PROMIS UE in younger, high-functioning patients are warranted. Finally, the PROMIS PF CAT exhibited a low question burden relative to traditional PRO instruments without the loss of reliability

Statin Use and Risk of Sepsis After Percutaneous Nephrolithotomy

Purpose: To examine the association between statin medication use and sepsis risk after percutaneous nephrolithotomy (PCNL). Materials and Methods: Using medical claims data, we identified working-age adults with urinary stone disease who were treated with PCNL. Among this cohort, we determined which patients had a prescription fill for a statin agent that encompassed their surgery date. We then fitted logistic regression models to examine for differences in rates of postoperative sepsis between statin users and nonusers. In addition, we evaluated the frequency of nonfebrile urinary tract infections (UTIs) and intensive care unit (ICU) services utilization and hospital length of stay (LOS) as a function of statin use. Results: During the study period, at total of 2046 patients underwent PCNL, 382 (18.7%) of whom had a prescription fill for a statin agent preceding their surgery. The overall rate of sepsis in this population was 3.8%. After adjusting for patient health status and sociodemographic factors, the rate of postoperative sepsis was comparable between statin users and nonusers (5.3% vs 3.5%, respectively; P=0.105). In addition, UTI and ICU utilization rates did not relate to statin use (P>0.05 for all associations). Adjusted hospital LOS was shorter among statin users, but the difference was clinically trivial (3.6 vs 4.1 days; P=0.007). Conclusions: Statin use is not associated with reductions in postoperative sepsis, nonfebrile UTIs, ICU utilization, or hospital LOS after PCNL. To increase the safety of PCNL, urologists will have to consider other processes of care (e.g., clinical care pathways).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140081/1/end.2015.0042.pd

Scaling Studies for High Temperature Test Facility and Modular High Temperature Gas-Cooled Reactor

The Oregon State University (OSU) High Temperature Test Facility (HTTF) is an integral experimental facility that will be constructed on the OSU campus in Corvallis, Oregon. The HTTF project was initiated, by the U.S. Nuclear Regulatory Commission (NRC), on September 5, 2008 as Task 4 of the 5-year High Temperature Gas Reactor Cooperative Agreement via NRC Contract 04-08-138. Until August, 2010, when a DOE contract was initiated to fund additional capabilities for the HTTF project, all of the funding support for the HTTF was provided by the NRC via their cooperative agreement. The U.S. Department of Energy (DOE) began their involvement with the HTTF project in late 2009 via the Next Generation Nuclear Plant (NGNP) project. Because the NRC's interests in HTTF experiments were only centered on the depressurized conduction cooldown (DCC) scenario, NGNP involvement focused on expanding the experimental envelope of the HTTF to include steady-state operations and also the pressurized conduction cooldown (PCC)

The Prevalence and Clinical Implications of Comorbid Back Pain in Shoulder Instability: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.

Background:Understanding predictors of pain is critical, as recent literature shows that comorbid back pain is an independent risk factor for worse functional and patient-reported outcomes (PROs) as well as increased opioid dependence after total joint arthroplasty. Purpose/Hypothesis:The purpose of this study was to evaluate whether comorbid back pain would be predictive of pain or self-reported instability symptoms at the time of stabilization surgery. We hypothesized that comorbid back pain will correlate with increased pain at the time of surgery as well as with worse scores on shoulder-related PRO measures. Study Design:Cross-sectional study; Level of evidence, 3. Methods:As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients consented to participate in pre- and intraoperative data collection. Demographic characteristics, injury history, preoperative PRO scores, and radiologic and intraoperative findings were recorded for patients undergoing surgical shoulder stabilization. Patients were also asked, whether they had any back pain. Results:The study cohort consisted of 1001 patients (81% male; mean age, 24.1 years). Patients with comorbid back pain (158 patients; 15.8%) were significantly older (28.1 vs 23.4 years; P < .001) and were more likely to be female (25.3% vs 17.4%; P = .02) but did not differ in terms of either preoperative imaging or intraoperative findings. Patients with self-reported back pain had significantly worse preoperative pain and shoulder-related PRO scores (American Shoulder and Elbow Surgeons score, Western Ontario Shoulder Instability Index) (P < .001), more frequent depression (22.2% vs 8.3%; P < .001), poorer mental health status (worse scores for the RAND 36-Item Health Survey Mental Component Score, Iowa Quick Screen, and Personality Assessment Screener) (P < .01), and worse preoperative expectations (P < .01). Conclusion:Despite having similar physical findings, patients with comorbid back pain had more severe preoperative pain and self-reported symptoms of instability as well as more frequent depression and lower mental health scores. The combination of disproportionate shoulder pain, comorbid back pain and mental health conditions, and inferior preoperative expectations may affect not only the patient's preoperative state but also postoperative pain control and/or postoperative outcomes

Killing Tensors and Conformal Killing Tensors from Conformal Killing Vectors

Koutras has proposed some methods to construct reducible proper conformal Killing tensors and Killing tensors (which are, in general, irreducible) when a pair of orthogonal conformal Killing vectors exist in a given space. We give the completely general result demonstrating that this severe restriction of orthogonality is unnecessary. In addition we correct and extend some results concerning Killing tensors constructed from a single conformal Killing vector. A number of examples demonstrate how it is possible to construct a much larger class of reducible proper conformal Killing tensors and Killing tensors than permitted by the Koutras algorithms. In particular, by showing that all conformal Killing tensors are reducible in conformally flat spaces, we have a method of constructing all conformal Killing tensors (including all the Killing tensors which will in general be irreducible) of conformally flat spaces using their conformal Killing vectors.Comment: 18 pages References added. Comments and reference to 2-dim case. Typos correcte