Physical Therapy

K + channels play important roles in skeletal muscle contraction by regulating action potential duration. Blocking these channels, for example with 3,4-diaminopyridine (DAP), augments muscle force considerably, and these force increases are maintained well during fatigue-inducing contractions. The present study tested the hypothesis that K + channel blockade also improves force of previously fatigued muscle. Rat diaphragm underwent fatigue-inducing stimulation in vitro with four different stimulation protocols consisting of 20 Hz vs. 50 Hz trains and 1 min vs. 4 min stimulation durations. DAP administered at the onset of the recovery period produced significant force increases irrespective of the amount of antecedent force loss. These force gains considerably exceeded those resulting from normal force recovery in untreated muscle. Furthermore contraction time was prolonged by DAP in all cases, and half-relaxation time was prolonged by DAP in most cases. Several differences were found compared with previous studies of DAP in fresh muscle, including smaller magnitude and slower time course of force increases. Intracellular electrophysiological recordings found smaller effects of DAP on action potential overshoot and time-depolarization integral in previously stimulated compared with fresh muscle. These data indicate that K + channel blockade does indeed increase force of fatigued diaphragm, but to an attenuated extent relative to its effects on non-fatigued muscle, which can be explained on the basis of electrophysiological findings. Nonetheless DAP-induced force increases were usually sufficient to restore force to values present prior to the onset of fatigue-inducing stimulation. Published by Elsevier B.V.

Rising education costs are an imperative problem in the United States.Over the last 20 years, the cost for a student to attend college has increased 439%. Currently, the United States is ranked 10th out of 30 countries for the number 25 to 34-year olds that hold associate degrees or higher. However, Americans are continually falling behind in education. This speech discusses the problems and causes associated with rising tuition costs and also proposes solutions to decrease the costs of higher education.

Mitochondria have many important functions within a cell, such as ATP production, regulation of Ca2+ homeostasis and apoptosis. The purpose of this project is to generate cell lines that lack mitochondria. These cell lines would be useful in studies involving mechanisms like metabolism, homeostasis, and apoptosis. The MDA-MB-231 human breast cancer cell line was selected for these studies and grown in normal growth media supplemented with ethidium bromide and uridine. After a period of 30 days, clonal cells were selected for serial dilutions (designated 231A-P). These clonal cell lines were then used to isolate genomic DNA and RNA for PCR and RT-PCR studies. Primers were designed to the mitochondrial and nuclear genomes as well as mRNA (cDNA) from these respective genomes. ND5, ND4, and Cytochrome b genes were amplified from the mitochondrial genome and the cystic fibrosis gene was amplified from the nuclear genome. PCR and RT-PCR were carried out with optimized conditions for primer sets. This paper will report the results of these initial findings. We expect to see no mitochondria as detected by PCR and RT- PCR.

Today breast cancer is the second most diagnosed cancer in women, accounting for 1 in 4 cancers diagnosed. Some oncologists have suggested that the poor prognosis of certain cancers may be blamed on current standardized cancer treatments. PARP inhibitor, an anticancer drug that affects base excision repair in DNA of cancer cells has been a proposed solution to increasing cancer survival rates when used in conjunction with standardized cancer treatments. This speech discusses the problems associated with standardized cancer treatments and how PARP inhibitor can be a contributor to maximize these treatments.

Triple negative (TN) breast cancer accounts for 10% of all sporadic breast cancers and lack three specific cellular receptors, estrogen receptor-α, progesterone receptor, and HER2 receptor/NEU oncogene (termed ER-, PR-, HER2). Interestingly, preclinical research has found that TN breast cancers are phenotypically similar to BRCA1 and BRCA2 mutated breast cancers. Research also suggests that the BRCA1 gene is involved in several types of DNA repair mechanisms including double-stranded break repair, nucleotide excision repair, and DNA cross-link repair and that mutations in BRCA1 result in defects in DNA repair. These mutations have been shown to be highly sensitive to chemotherapy drugs such as mitomycin C and cisplatin. Recently, it has been indicated that drugs called Poly (ADP-ribose) polymerase (PARP) inhibitors may have a primary role in treating BRCA mutated cancer. This review discusses the biological mechanisms of PARP and PARP inhibition as well as PARP inhibitor’s implications and limitations.

The basal-like subtype of breast cancer is characterized by a “triple negative” (TN) phenotype (i.e. negative for estrogen, progesterone, and HER2 receptors). These cancers are often associated with a poor outcome and are resistant to current treatment. It has been shown that TN breast cancers are defective in repairing oxidative DNA damage through the base-excision repair (BER) pathway. PARP1 is a member of a large family of enzymes that can detect single strand breaks within the DNA and mediates recruitment of BER elements. In recent clinical trials, it has been shown that TN breast cancers are responsive to PARP inhibitors. However, the exact mechanism of how PARP inhibitor interacts with the BER pathway has not yet been elucidated. In this study, we investigated whether the inhibition of PARP will lead to increased sensitivity to H2O2, an indicator of reduced BER. We found that TN HCC1806 were more sensitive to the PARP inhibitor PJ34 and to hydrogen peroxide (H2O2) than luminal MCF7 cells. However, when cells were treated with PARP inhibitor followed by H2O2, we found that at a ≥IC50 there was an antagonistic effect of PJ34 on H2O2 sensitivity. HCC1806 PARP1 and 2 knockdowns were also tested for H2O2 sensitivity. PARP2 knockdowns showed increased sensitivity to H2O2 compared to Non-Silencing and PARP1 knockdowns, likely explained by the fact that PARP protein levels are decreased by 80% in PARP2 knockdowns and only 20% in PARP1 knockdowns. This increased H2O2 sensitivity in PARP2 knockdowns suggests a role for PARP in BER.

The basal-like subtype of breast cancer is characterized by a “triple negative” (TN) phenotype (i.e. negative for estrogen, progesterone, and HER2 receptors). These cancers are often associated with a poor outcome and are resistant to current treatment. It has been shown that TN breast cancers are defective in repairing oxidative DNA damage through the base-excision repair (BER) pathway. PARP1 is a member of a large family of enzymes that can detect single strand breaks within the DNA and mediates recruitment of BER elements. In recent clinical trials, it has been shown that TN breast cancers are responsive to PARP inhibitors. However, the exact mechanism of how PARP inhibitor interacts with the BER pathway has not yet been elucidated. In this study, we investigated whether the inhibition of PARP will lead to increased sensitivity to H2O2, an indicator of reduced BER. We found that TN HCC1806 were more sensitive to the PARP inhibitor PJ34 and to hydrogen peroxide (H2O2) than luminal MCF7 cells. However, when cells were treated with PARP inhibitor followed by H2O2, we found that at a ≥IC50 there was an antagonistic effect of PJ34 on H2O2 sensitivity. HCC1806 PARP1 and 2 knockdowns were also tested for H2O2 sensitivity. PARP2 knockdowns showed increased sensitivity to H2O2 compared to Non-Silencing and PARP1 knockdowns, likely explained by the fact that PARP protein levels are decreased by 80% in PARP2 knockdowns and only 20% in PARP1 knockdowns. This increased H2O2 sensitivity in PARP2 knockdowns suggests a role for PARP in BER.

Mitochondria have many important functions within a cell, such as ATP production, regulation of Ca2+ homeostasis and apoptosis. The purpose of this project is to generate cell lines that lack mitochondria. These cell lines would be useful in studies involving mechanisms like metabolism, homeostasis, and apoptosis. The MDA-MB-231 human breast cancer cell line was selected for these studies and was grown in normal growth media supplemented with ethidium bromide and uridine. After a period of 30 days, clonal cells were selected for serial dilutions (designated 231A-P). These clonal cell lines were then used to isolate genomic DNA and RNA for PCR and RT-PCR studies.  Primers were designed to the mitochondrial and nuclear genomes as well as mRNA (cDNA) from these respective genomes. ND5, ND4, and cytochrome b genes were amplified from the mitochondrial genome and the cystic fibrosis gene was amplified from the nuclear genome. PCR and RT-PCR were carried out with optimized conditions for primer sets. We expect to see no mitochondria as detected by PCR and RT-PCR. This poster will report the results of these initial findings. This research was supported by NSF-REU grant #DBI0647160.

Mitochondria have many important functions within a cell, such as ATP production, regulation of Ca2+ homeostasis and apoptosis. The purpose of this project is to generate cell lines that lack mitochondria. These cell lines would be useful in studies involving mechanisms like metabolism, homeostasis, and apoptosis. The MDA-MB-231 human breast cancer cell line was selected for these studies and was grown in normal growth media supplemented with ethidium bromide and uridine. After a period of 30 days, clonal cells were selected for serial dilutions (designated 231A-P). These clonal cell lines were then used to isolate genomic DNA and RNA for PCR and RT-PCR studies.  Primers were designed to the mitochondrial and nuclear genomes as well as mRNA (cDNA) from these respective genomes. ND5, ND4, and cytochrome b genes were amplified from the mitochondrial genome and the cystic fibrosis gene was amplified from the nuclear genome. PCR and RT-PCR were carried out with optimized conditions for primer sets. We expect to see no mitochondria as detected by PCR and RT-PCR. This poster will report the results of these initial findings. This research was supported by NSF-REU grant #DBI0647160.

Triple negative (TN) breast cancer accounts for 10% of all sporadic breast cancers and lack three specific cellular receptors, estrogen receptor-α, progesterone receptor, and HER2 receptor/NEU oncogene (termed ER-, PR-, HER2). Interestingly, preclinical research has found that TN breast cancers are phenotypically similar to BRCA1 and BRCA2 mutated breast cancers. Research also suggests that the BRCA1 gene is involved in several types of DNA repair mechanisms including double-stranded break repair, nucleotide excision repair, and DNA cross-link repair and that mutations in BRCA1 result in defects in DNA repair. These mutations have been shown to be highly sensitive to chemotherapy drugs such as mitomycin C and cisplatin. Recently, it has been indicated that drugs called Poly (ADP-ribose) polymerase (PARP) inhibitors may have a primary role in treating BRCA mutated cancer. This review discusses the biological mechanisms of PARP and PARP inhibition as well as PARP inhibitor’s implications and limitations.

Introduction: Activities requiring repeated and asymmetrical trunk movements are associated with an increased risk for low back pain (LBP). One potential reason for this is that people develop specific movement strategies related to the repetitive movements. Over time, the strategies are generalized across multiple activities. The use of these strategies is thought to contribute to tissue adaptations that eventually become impairments. Both the strategies and resulting impairments are proposed to be evident during an examination and provide insight into the specific LBP condition. The purpose of this secondary analysis was to examine the relationship between the specific activities a person with LBP performs regularly, such as participation in a rotation-related sport, and the impairments assessed on examination. We hypothesized that people with LBP who participated in a rotation-related sport would display more (1) rotation-related impairments, and (2) asymmetry of these impairments than people without LBP who did not participate in the sport.
Methods: Back healthy controls (BHC) and people with LBP were recruited and matched based on gender, age, and activity level. Participants completed self-report measures and participated in a standardized clinical examination. Self-report measures included (1) a demographic and LBP history form, and (2) the Baecke Habitual Activity Questionnaire. Participants with LBP also completed a sport-related activity questionnaire and the Oswestry LBP Disability Questionnaire. The number of impairments exhibited during the clinical examination was calculated for each participant. Independent samples t-tests were conducted to compare (1) the total number of rotation-related impairments, and (2) asymmetry of these impairments between the BHC and LBP groups. Effect sizes were calculated using Cohen’s d.
Results: Data from 55 participants with LBP and 42 BHC were analyzed. Compared to the BHCs, participants with LBP displayed a significantly higher number of (1) rotation-related impairments (LBP: 6.49 ± 2.29, BHC: 4.14 ± 2.35; 95% CI for mean difference = 3.29 to 1.40; Cohen’s d = 1.01), and (2) asymmetry of rotation-related impairments (LBP: 3.73 ± 1.66, BHC: 2.76 ± 1.87; 95% CI for mean difference = 1.68 to 0.25; Cohen’s d = 0.55).
Discussion: As hypothesized, participants with LBP displayed a significantly greater number and asymmetry of rotation-related impairments than BHCs. Interestingly, the BHCs also displayed some of the same impairments and asymmetry as the participants with LBP. These data suggest that although both groups display movement impairments, participation in an activity in which the movement impairments are used repetitively may increase the number and asymmetry, and potentially contribute to a LBP condition. Future research should include prospective investigation to better understand the relationships between impairments, activity type, and LBP. The ultimate goal would be to identify the specific impairments to target for rehabilitative and preventative treatment of LBP. These studies could have important implications for people who regularly participate in work and daily activities requiring repetitive trunk movements.

Objective: To determine if people with low back pain (LBP) who regularly participated in a rotation-related activity displayed more rotation-related impairments than people without LBP who did not participate in the activity.

Design: Secondary analysis of data from a case-control study.

Setting: Musculoskeletal analysis laboratory at an academic medical center.

Participants: A convenience sample of 55 participants with chronic or recurrent LBP who participated in a rotation-related sport that was associated with their LBP symptoms and 42 back healthy controls
(BHC). Participants were matched based on age, gender, and activity level.

Interventions: Not applicable.

Main Outcome Measures: The total number of (1) rotation-related impairments, and (2) asymmetric rotation-related impairments identified during a standardized clinical examination.

Results: Compared to the BHC group, the LBP group displayed a significantly higher number of (1) rotation-related impairments (LBP: 6.49 ± 2.29, BHC: 4.14 ± 2.35; 95% CI for mean difference = 3.29 to
1.40; Cohen's d = 1.01) and (2) asymmetry of rotation-related impairments (LBP: 3.73 ± 1.66, BHC: 2.76 ± 1.87; 95% CI for mean difference = 1.68 to 0.25; Cohen's d = 0.55).

Conclusions: Compared to the BHC group, the LBP group displayed more total rotation-related impairments and asymmetry of impairments. These findings suggest that participation in a rotation related activity may increase the number and asymmetry of impairments identified on examination, and could potentially contribute to a LBP condition.

The Mini-BESTest is a relatively new outcome measure used to measure dynamic balance. This talk discusses advantages and disadvantages of using the Mini-BESTest. Reliability, validity, and accuracy of the Mini-BEST are compared with other commonly used balance outcome measures. Finally, clinical applicability of the outcome measure is discussed.

Deep vein thrombosis (DVT) is a relatively common disease encountered by physical therapists, especially in the outpatient orthopedic settings. If a DVT is missed by a healthcare professional, a patient is at increased risk for pulmonary embolism, post-phlebitic
syndrome, or chronic thromboembolic. This talk discusses the natural history of DVT, diagnosis of DVT, and clinical prediction rules physical therapists can use to help guide decisions in referring patients for further testing. Finally, 2 clinical cases are discussed.

Patellofemoral pain (PFP) accounts for 25% of all knee pain presentations in active individuals to outpatient physical therapy clinics.  Historically, the etiology of PFP has been attributed to altered patellofemoral joint mechanics and stresses. However, recent research has suggested insufficient strength of the proximal hip musculature may contribute to PFP.  Many studies exploring the effectiveness of hip strengthening include confounding interventions such as hip strengthening combined with quadriceps strengthening. Therefore, there is a lack of literature exploring the effectiveness of hip strengthening as an isolated intervention in the treatment of PFP. A structured review was conducted to answer the following clinical question: “What is the effect of hip strengthening on pain and function in the rehabilitation of patients under 45 years of age with patellofemoral pain?”
Based on results of 11 studies, there is moderate evidence to suggest that hip strengthening is effective in (1) decreasing general pain and pain during activity and (2) improving generalized lower extremity function during activities such as squatting, walking, and stair negotiation, functional strength and health status in people with PFP. The population that best applies to this review includes active and sedentary men and women 22-35 years old with chronic PFP. Additionally, this review indicates that hip strengthening alone or in combination with quadriceps strengthening or trunk stability training is more effective at improving pain and function compared to quadriceps strengthening alone.

Patellofemoral pain (PFP) accounts for 25% of all knee pain presentations in active individuals to outpatient physical therapy clinics.  Historically, the etiology of PFP has been attributed to altered patellofemoral joint mechanics and stresses. However, recent research has suggested insufficient strength of the proximal hip musculature may contribute to PFP.  Many studies exploring the effectiveness of hip strengthening include confounding interventions such as hip strengthening combined with quadriceps strengthening. Therefore, there is a lack of literature exploring the effectiveness of hip strengthening as an isolated intervention in the treatment of PFP. A structured review was conducted to answer the following clinical question: “What is the effect of hip strengthening on pain and function in the rehabilitation of patients under 45 years of age with patellofemoral pain?”
Based on results of 11 studies, there is moderate evidence to suggest that hip strengthening is effective in (1) decreasing general pain and pain during activity and (2) improving generalized lower extremity function during activities such as squatting, walking, and stair negotiation, functional strength and health status in people with PFP. The population that best applies to this review includes active and sedentary men and women 22-35 years old with chronic PFP. Additionally, this review indicates that hip strengthening alone or in combination with quadriceps strengthening or trunk stability training is more effective at improving pain and function compared to quadriceps strengthening alone.

This document is an appendix further describing the studies utilized to reach the answer to the clinical question.

Patellofemoral pain (PFP) accounts for 25% of all knee pain presentations in active individuals to outpatient physical therapy clinics.  Historically, the etiology of PFP has been attributed to altered patellofemoral joint mechanics and stresses. However, recent research has suggested insufficient strength of the proximal hip musculature may contribute to PFP.  Many studies exploring the effectiveness of hip strengthening include confounding interventions such as hip strengthening combined with quadriceps strengthening. Therefore, there is a lack of literature exploring the effectiveness of hip strengthening as an isolated intervention in the treatment of PFP. A structured review was conducted to answer the following clinical question: “What is the effect of hip strengthening on pain and function in the rehabilitation of patients under 45 years of age with patellofemoral pain?”
Based on results of 11 studies, there is moderate evidence to suggest that hip strengthening is effective in (1) decreasing general pain and pain during activity and (2) improving generalized lower extremity function during activities such as squatting, walking, and stair negotiation, functional strength and health status in people with PFP. The population that best applies to this review includes active and sedentary men and women 22-35 years old with chronic PFP. Additionally, this review indicates that hip strengthening alone or in combination with quadriceps strengthening or trunk stability training is more effective at improving pain and function compared to quadriceps strengthening alone.

Objective
To determine if people with low back pain (LBP) who regularly participated in a rotation-related activity displayed more rotation-related impairments than people without LBP who did and did not participate in the activity.

Design
Secondary analysis of data from a case-control study.

Setting
Musculoskeletal analysis laboratory at an academic medical center.

Participants
A convenience sample of 55 participants with LBP who participated in a rotation-related sport, 26 back healthy controls who participated in a rotation-related sport (BHC+RRS) and 42 back healthy controls who did not participate in a rotation-related sport (BHC-RRS). Participants were matched based on age, gender, and activity level.

Interventions
Not applicable.

Main Outcome Measures
The total number of rotation-related impairments and asymmetric rotation-related impairments identified during a standardized clinical examination.

Results
Compared to the BHC-RRS group, both the LBP and BHC+RRS groups displayed significantly more (1) rotation-related impairments (LBP: p<.001; BHC+RRS: p=.015) (2) asymmetric rotation-related impairments (LBP: p=.006; BHC+RRS: p=.020) and (3) rotation-related impairments with trunk movement tests (LBP: p=.002; BHC+RRS: p<.001). The LBP group had significantly more rotation-related impairments with extremity movement tests than both of the back healthy groups (BHC+RRS: p=.011; BHC-RRS: p<.001).

Conclusions
LBP and BHC+RRS groups demonstrated a similar number of total rotation-related impairments and asymmetric rotation-related impairments, and these numbers were greater than those of the BHC-RRS group. Compared to people without LBP, people with LBP displayed more rotation-related impairments when moving an extremity. These findings suggest that impairments associated with extremity movements may be associated with having a LBP condition.

Key Words
low back pain; spine; rotation; sports

Low back pain (LBP) is a common musculoskeletal condition that affects 60-80% of the US population at some point during adulthood. Because of its prevalence and its course, LBP is a costly health conditions, yet no optimal treatments have been shown to consistently improve its clinical course. Additionally, one of the most important risk factors for LBP development is a previous history of LBP. Therefore, it is essential to prevent this first episode from occurring.

The pilot program proposed in this application aims to incorporate peer education, training and lab sessions, and lifting equipment to promote back protective behaviors and change mindsets among staff at high risk for occupational low back injury in four BJC-affiliated hospitals. Currently, BJC handles all occupational low back injuries after they occur. This program aims to change this practice by addressing the prevention of LBP. Administered by the BJC Ergonomics Department, the program will strive to decrease the number and cost of occupational-related low back injuries in the workplace. Our strategies include an assessment of the attitudes and openness to ceiling lift use, education on the benefits of ceiling lifts and back safety, and adjustment of the ratio of ceiling lifts in target hospitals. Data analysis and processing are recommended as the program progresses and at program completion.

This document provides recommendations for planning, implementing, and evaluating pilot testing of this program.  Additionally, it provides information on causal framework, logic model, timelines, budgeting, and potential outcome measures for the program.