Selection for increased voluntary wheel-running affects behavior and brain monoamines in mice.

Selective-breeding of house mice for increased voluntary wheel-running has resulted in multiple physiological and behavioral changes. Characterizing these differences may lead to experimental models that can elucidate factors involved in human diseases and disorders associated with physical inactivity, or potentially treated by physical activity, such as diabetes, obesity, and depression. Herein, we present ethological data for adult males from a line of mice that has been selectively bred for high levels of voluntary wheel-running and from a non-selected control line, housed with or without wheels. Additionally, we present concentrations of central monoamines in limbic, striatal, and midbrain regions. We monitored wheel-running for 8 weeks, and observed home-cage behavior during the last 5 weeks of the study. Mice from the selected line accumulated more revolutions per day than controls due to increased speed and duration of running. Selected mice exhibited more active behaviors than controls, regardless of wheel access, and exhibited less inactivity and grooming than controls. Selective-breeding also influenced the longitudinal patterns of behavior. We found statistically significant differences in monoamine concentrations and associated metabolites in brain regions that influence exercise and motivational state. These results suggest underlying neurochemical differences between selected and control lines that may influence the observed differences in behavior. Our results bolster the argument that selected mice can provide a useful model of human psychological and physiological diseases and disorders.

Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology.

AIMS/HYPOTHESIS: Methylglyoxal (MG) is an important precursor for AGEs. Normally, MG is detoxified by the glyoxalase (GLO) enzyme system (including component enzymes GLO1 and GLO2). Enhanced glycolytic metabolism in many cells during diabetes may overpower detoxification capacity and lead to AGE-related pathology. Using a transgenic rat model that overexpresses GLO1, we investigated if this enzyme can inhibit retinal AGE formation and prevent key lesions of diabetic retinopathy. METHODS: Transgenic rats were developed by overexpression of full length GLO1. Diabetes was induced in wild-type (WT) and GLO1 rats and the animals were killed after 12 or 24 weeks of hyperglycaemia. N ε)-(Carboxyethyl)lysine (CEL), N(ε)-(carboxymethyl)lysine (CML) and MG-derived-hydroimidazalone-1 (MG-H1) were determined by immunohistochemistry and by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS). Müller glia dysfunction was determined by glial fibrillary acidic protein (GFAP) immunoreactivity and by spatial localisation of the potassium channel Kir4.1. Acellular capillaries were quantified in retinal flat mounts. RESULTS: GLO1 overexpression prevented CEL and MG-H1 accumulation in the diabetic retina when compared with WT diabetic counterparts (p < 0.01). Diabetes-related increases in Müller glial GFAP levels and loss of Kir4.1 at the vascular end-feet were significantly prevented by GLO1 overexpression (p < 0.05) at both 12- and 24-week time points. GLO1 diabetic animals showed fewer acellular capillaries than WT diabetic animals (p < 0.001) at 24 weeks' diabetes. CONCLUSIONS/INTERPRETATION: Detoxification of MG reduces AGE adduct accumulation, which, in turn, can prevent formation of key retinal neuroglial and vascular lesions as diabetes progresses. MG-derived AGEs play an important role in diabetic retinopathy.

Müller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products.

AIMS/HYPOTHESIS: The impact of AGEs and advanced lipoxidation end-products (ALEs) on neuronal and Müller glial dysfunction in the diabetic retina is not well understood. We therefore sought to identify dysfunction of the retinal Müller glia during diabetes and to determine whether inhibition of AGEs/ALEs can prevent it. METHODS: Sprague-Dawley rats were divided into three groups: (1) non-diabetic; (2) untreated streptozotocin-induced diabetic; and (3) diabetic treated with the AGE/ALE inhibitor pyridoxamine for the duration of diabetes. Rats were killed and their retinas were evaluated for neuroglial pathology. RESULTS: AGEs and ALEs accumulated at higher levels in diabetic retinas than in controls (p < 0.001). AGE/ALE immunoreactivity was significantly diminished by pyridoxamine treatment of diabetic rats. Diabetes was also associated with the up-regulation of the oxidative stress marker haemoxygenase-1 and the induction of glial fibrillary acidic protein production in Müller glia (p < 0.001). Pyridoxamine treatment of diabetic rats had a significant beneficial effect on both variables (p < 0.001). Diabetes also significantly altered the normal localisation of the potassium inwardly rectifying channel Kir4.1 and the water channel aquaporin 4 to the Müller glia end-feet interacting with retinal capillaries. These abnormalities were prevented by pyridoxamine treatment. CONCLUSIONS/INTERPRETATION: While it is established that AGE/ALE formation in the retina during diabetes is linked to microvascular dysfunction, this study suggests that these pathogenic adducts also play a role in Müller glial dysfunction.

Advanced glycation end products accumulate in the reproductive tract of men with diabetes.

Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable effects of diabetes on sperm function. Specifically, a recent study has found a significantly higher sperm nuclear DNA fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and nine non-diabetic subjects. CML immunoreactivity was found throughout the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells cytoplasm and nuclei of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non-diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggest that these compounds may play a hitherto unrecognized role in male infertility.

Selection for aerobic capacity affects corticosterone, monoamines and wheel-running activity.

A positive genetic relationship between aerobic capacity and voluntary exercise has been suggested from earlier studies of mice selected for increased wheel-running activity. To further investigate the relationship between aerobic capacity and exercise behavior, wheel-running activity was studied in female rats bidirectionally selected for intrinsic aerobic capacity (high capacity runners - HCR; low capacity runners - LCR). Aerobic capacity was measured using a forced treadmill paradigm; the subpopulations of animals used in this experiment exhibited a 471% difference in endurance capacity. Rats were housed individually, with or without access to running wheels. Wheel-running activity was recorded and analyzed from weeks two through seven during an eight-week trial to determine voluntary activity levels. HCR animals exhibited 33% greater total wheel-running distance per day compared to LCR rats (16,838.7+1337.30 m versus 12,665.8+893.88 m), which was due to the HCR rats exhibiting increases in both running speed and duration over LCR rats. Differences in the intermittency of wheel running were also observed. HCR rats engaged in more bouts of running per day than LCR rats, and trended towards running faster, for more time, and for longer distances during bouts of running than LCR rats. Following the running trial, measurement of plasma corticosterone concentration and striatal dopaminergic activity showed differences between HCR and LCR rats, suggesting a divergence of physiological systems that could potentially influence locomotor behaviors in these lines. These results are consistent with earlier work, and suggest an evolutionarily conserved relationship between physiological capacity and behavioral activity of exercise.

Guidance hypothesis with verbal feedback in learning a palpation skill.

OBJECTIVE: To investigate whether a force application of a novel motor skill was simple or complex and to determine the appropriate level of feedback during training. The objective was to determine the effects of various amounts of knowledge of results (KR) on learning a novel skill that is frequently taught in chiropractic for the assessment of vertebral motor unit dysfunction. METHODS: Thirty-five active subjects were taught the novel skill of spring testing to a particular force range through 9 or 10 teaching sessions over a 2-week period (a school holiday limited some to only 9 sessions). To determine the particular force range, an initial phase of the study involved a licensed and practicing clinician performing motion palpation spring testing of the thoracic spine of a prone subject. The data from a total of 47 pushes throughout the thoracic spine were recorded, and the mean force and standard deviation were calculated. The second phase of the study used the obtained mean and standard deviation for teaching the force of prone thoracic spine motion palpation to 35 active subjects by administering spring testing to 35 passive subjects. The active subjects were randomly divided into 4 groups, with each receiving a varying amount of verbal feedback to move toward the target force of their learned skill. Each passive subject was laid prone on an instrumented adjusting table. Group 1 received the least amount of feedback while learning the novel skill. Groups 2 and 3 received more frequent, intermittent feedback while learning the skill, and group 4 received constant, frequent feedback during each of the 10 teaching sessions. All subjects returned within 2 weeks for 2 retention trials to determine the efficacy of the learned skill. RESULTS: The mean force determined was 143 N with a standard deviation of 14 N. Each subject was taught spring testing within this target range. The 2 final retention trials showed group 3 to have demonstrated the most targeted retention of the learned motor skill. These subjects exhibited the closest force range to the target for the motor skill learned and fewer changes in standard deviation compared with their acquisition trials and thus the highest retention. Group 4, receiving 100% feedback, demonstrated the most accurate spring testing during the acquisition trials, but the subjects did not effectively demonstrate when compared on acquisition and retention trials. CONCLUSION: The results of this study show data to be consistent with the guidance hypothesis in learning a novel motor skill. The constant KR feedback is beneficial for learning when used to reduce error during practice but detrimental when relied upon for retention and learning. These data suggest the necessity of using motor skill development learning theory in the teaching of chiropractic.

An audit of medicolegal conferencing.

In the English civil justice system, experts involved in a case are now commonly required to confer before the hearing and identify the areas of agreement and disagreement. A prospective study of 50 consecutive medicolegal conferences of experts was undertaken, with a view to defining their benefits, weaknesses and the optimum conference format. A record was kept of the dates of first instruction, court deadlines, and date, time and duration of conferences, together with related calls and correspondence. The manner of preparation of the statement was noted, the level of agreement/disagreement, any compromise, any later modifications of the draft, and the author's fees. Subsequently the instructing solicitors were asked to comment on the suitability of the joint statement and its contribution to settlement. Medicolegal conferencing is time-consuming and expensive. It may be of limited value where there is little or no difference of opinion, either between experts in a single field or between experts in different fields. The instructing solicitors must ensure that the participants receive, in advance of the conference, copies of all relevant documents including medical reports and medical records. An agenda is helpful in ensuring that matters of importance are not overlooked. Conferences are more effective when held in person than when conducted by telephone. The joint statement is best dictated in the presence of all participants during or after the conference. To ensure the most efficient and economical use of consultant time a formal combined audit of conferencing should be undertaken by the medical and legal professions.

Case report: Myofascial pain syndrome: a double crush-like appearance.

OBJECTIVE: To discuss the case of a patient with myofascial pain syndrome that appeared similar to double crush syndrome. CLINICAL FEATURES: This is a case report of a 45-year old female who presents to the private practice clinic with the same signs and symptoms of carpal tunnel syndrome, 1 year post-carpaltunnel surgery. The history is consistent with injuries that result in double crush syndrome and thoracic outlet syndrome. The patient history includes a motor vehicle accident (MVA) in 1963 that resulted in a prolonged hospital stay and fracture of a cervical vertebral (C4) body. She fractured the olecranon process of the right elbow during a fall in 1970's. She has smoked approximately 1 pack a day for 20 years. Her job involves long periods of sitting at a keyboard and in a car. All of these portions of the patient history are possible factors in the clinical signs and symptoms of double crush syndrome. INTERVENTION AND OUTCOME: Treatment involved chiropractic manipulation and physical therapy modalities for the elimination of pain and returning the patient's full range of motion in the wrist, elbow, shoulder and cervical spine. After range of motion was restored, a home exercise program was initiated. The home exercise program included a return to past sporting activity and active, resistive (Theraciser band) activities for the elbow and cervical spine. Also a reduction in smoking was initiated as part of the patient's treatment plan. CONCLUSION: It is our contention that patients who have electromyographic (EMG) demonstrable carpal tunnel syndrome need a cervical spine workup and a period of conservative care to include skilled manipulation, physical therapy and home exercises before surgery is recommended.

Intra-instrument reliability of 4 goniometers.

BACKGROUND: Cervical spine ROM movements taken accurately with reliable measuring devices are important in outcome measures as well as in measuring disability. OBJECTIVE: To compare the active cervical spine ROM in healthy young adult population using 4 different goniometers. METHODS: Subjects were tested during active cervical spine ROM. The devices were a single hinge inclinometer, single bubble carpenter's inclinometer, dual bubble goniometers and Cybex EDI 320 electrical inclinometer. All subjects were tested for rotational limits along each of the orthogonal axes of movement. There are 3 trials for each movement direction, except rotation was not measured with the Cybex as per manual suggestions. The subjects were randomly assigned to the sequence of devices. SUBJECTS: Twenty-seven student volunteers (19 men and 8 women) were tested. Ages ranged from 21 to 41, mean age of 27.6 years of age. DATA: Active cervical spine ROM trials for each measurement was used to calculate mean and standard deviation. An overall analysis of variance (ANOVA) and Bonferroni adjusted T-test were determined in order to calculate reliability and significance. DISCUSSION: The cost of the instruments were not used in determining reliability or significance. The single hinge inclinometer was found to be a reliable measure but not likely valid. The Cybex EDI 320 was found to be the best measuring device; however, the 2 instruments whose cost were in-between the single hinge inclinometer and the electrical goniometer were just as reliable as the more expensive device. The AMA Guides of Impairment were used as the normative data to compare these devices. CONCLUSION: Since the devices could measure reliably, whether expensive or more cost effective for students they would likely make adequate devices for training students on the methods for measuring ROM. There is previous data to suggest that older populations have gender differences and age differences with ROM. This study could not measure that and would make a useful follow-up study.

The use of Learning and Study Strategies Inventory (LASSI) as a predictor for success or failure on part I of the National Board of Chiropractic Examiners Test.

INTRODUCTION: The need for each chiropractic student to pass the National Chiropractic Board of Examiners (NCBE) exams is of great importance in their educational process. To date, no literature has evaluated the effectiveness of any outcome in predicting the success or failure on the NCBE exams. The Learning and Study Strategies Inventory (LASSI) was developed to assess students' learning and studying strategies. In this study, the LASSI and NCBE Part 1 scores and entering and cumulative grade point averages (GPAs) were used to assess any correlations related to NCBE scores. METHODS: The LASSI was administered to a group of trimester-6 students at Texas Chiropractic College after their completion of Part 1 of NCBE exams. The scores were analyzed by computer and appropriate statistical procedures were performed. RESULTS: Moderately high correlations were found with NCBE scores and each component of the LASSI. There were also moderately high correlations found with the NCBE scores and cumulative GPAs. Low correlations were found with NCBE scores and entering GPAs. CONCLUSIONS: Because of the high correlation of NCBE scores and the LASSI scores, it is recommended that this test be introduced to first-trimester students and that follow-up correlations be performed with NCBE scores, GPAs and LASSI scores. An elective course for students that perform poorly on LASSI could be developed to aid students weak in study skills and strategies. The need for further studies includes the evaluation of students put through the LASSI and preparation course as it relates to their NCBE scores.

Incidence of sporting injury in New Zealand youths aged 6-15 years.

OBJECTIVE: To document the incidence of injury in 6-15 year olds playing rugby union, rugby league, and netball, and to identify the common mechanisms, sites, severity, and time of injury. METHODS: Cross sectional data were collected by trained observers who watched 258 games of rugby union, netball, and rugby league over a four week period. The condition of the injured participants was monitored until recovery. RESULTS: In total, 5174 players were observed and an injury rate of 18 per 1000 player hours was calculated. Of all observed injuries, 29% required some form of medical treatment. A significant difference (p<0.05) in the distribution of injury over the four quarters of the games was recorded, most occurring in the first three quarters. In total, 81% of the injuries were classified as contact injuries, and these mainly occurred through direct contact with the opposition. Of all observed injuries, 27% were recurrent. CONCLUSIONS: The incidence of injury in rugby union, netball, and rugby league is low for children aged between 6 and 15 years relative to adult rates.