Congruence and trajectories of device-measured and self-reported physical activity during therapy for early breast cancer.

PURPOSE: This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments. METHODS: Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman's Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance. RESULTS: Ninety-nine participants (median age = 50) were treated with adjuvant (N = 23), neoadjuvant (N = 21) or without chemotherapy (N = 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only "fair" (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p = 0.006, neoadjuvant: ∆ = 45min, p = 0.038) and lower in week 18 than in week 3 (∆ = 43min, p = 0.010). CONCLUSION: Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.

The transCampus Metabolic Training Programme Explores the Link of SARS-CoV-2 Virus to Metabolic Disease.

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.

Alignment sensing for optical cavities using radio-frequency jitter modulation.

Alignment sensing is often required in precision interferometry applications such as Advanced LIGO in order to achieve the optimum performance. Currently favored sensing schemes rely on the use of two separate radio-frequency (RF) quadrant photodetectors and Gouy phase telescopes to determine the alignment of a beam relative to an optical cavity axis. In this paper, we demonstrate an alternative sensing scheme that has potential advantages over the current standard schemes. We show that by using electro-optic beam deflectors to impose RF jitter sidebands on a beam, it is possible to extract full alignment signals for two in-line optical cavities from just one single-element photodetector in reflection of each cavity.

Serological, genomic and structural analyses of the major mite allergen Der p 23.

BACKGROUND: Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein. OBJECTIVE: This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population and to determine the structure for functional characterization. METHODS: IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7 and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analysed by X-ray crystallography and NMR. RESULTS: Despite a high prevalence of Der p 23, (75% vs. 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n = 47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, thirty fold less than Der p 1 and sevenfold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulphide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23. CONCLUSIONS AND CLINICAL RELEVANCE: Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expression of other Dermatophagoides allergens.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

Study participation rate of patients with acute spinal cord injury early during rehabilitation.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: To investigate the study participation rate of patients with acute spinal cord injury (SCI) early during rehabilitation after conveying preliminary study information. SETTING: Single SCI rehabilitation center in Switzerland. METHODS: Newly admitted acute SCI patients receive a flyer to inform them concerning the purpose of clinical research, patient rights and active studies. Upon patient request, detailed study information is given. The rate of patients asking for detailed information (study interest) and the rate of study participation was evaluated from May 2013 to October 2014. Furthermore, the number of patients not withdrawing consent to the utilization of coded health-related data was determined. RESULTS: The flyer was given to 144 of the 183 patients admitted during the observation period. A total of 96 patients (67%) were interested in receiving detailed information, and 71 patients (49%) finally participated in at least one study. The vast majority of patients (that is, 91%) did not withdraw consent for retrospective data analysis. An age over 60 years had a significantly (P⩽0.023) negative effect on study interest and participation, and the consent rate to retrospective data analysis was significantly (P<0.04) lower in patients older than 75 years. Study interest and participation were reduced more than 5 and 14-fold, respectively, in patients older than 60 years. CONCLUSIONS: The relatively low (approximately 50%) study participation rates of acute SCI patients should be considered when planning clinical trials. The recruitment of patients older than 60 years may be reduced substantially.

Parallel phase modulation scheme for interferometric gravitational-wave detectors.

Advanced LIGO (aLIGO) requires multiple frequency sidebands to disentangle all of the main interferometer's length signals. This paper presents the results of a risk reduction experiment to produce two sets of frequency sidebands in parallel, avoiding mixed 'sidebands on sidebands'. Two phase modulation frequencies are applied to separate Electro-Optic Modulators (EOMs), with one EOM in each of the two arms of a Mach-Zehnder interferometer. In this system the Mach-Zehnder's arm lengths are stabilized to reduce relative intensity noise in the recombined carrier beam by feeding a corrective control signal back to the Rubidium Titanyl Phosphate (RTP) EOM crystals to drive the optical path length difference to zero. This setup's use of the RTP crystals as length actuators provides enough bandwidth in the feedback to meet arm length stability requirements for aLIGO.

Delivering kidney cancer care in rural Central and Southern Illinois: a telemedicine approach.

There is a growing body of experience and research suggesting that telemedicine (video conferencing, smart phones and online patient portals) could be the solution to addressing gaps in the provision of specialised healthcare in rural areas. The proposed role of telemedicine in providing needed services in hard to reach areas is not new. The United States Telecommunication Act of 1996 provided the initial traction for telemedicine by removing important economic and legal obstacles regarding the use of technology in healthcare delivery. This initial ruling has been supplemented by the availability of federal funding to support efforts aimed at developing telemedicine in underserved areas. In this paper, we explore one aspect of disease disparity pertinent to rural Illinois (kidney cancer incidence and mortality) and describe how we are planning to use an existing telemedicine program at Southern Illinois University School of Medicine (SIUSOM) to improve kidney cancer (Kca) care in rural Illinois. This represents an example of the possible role of telemedicine in addressing healthcare disparities in rural areas/communities and provides a description of general challenges and barriers to the implementation and maintenance of such systems.

Cardiac characterization of 16 patients with large NF1 gene deletions.

The aim of this study was to characterize cardiac features of patients with neurofibromatosis 1 (NF1) and large deletions of the NF1 gene region. The study participants were 16 patients with large NF1 deletions and 16 age- and sex-matched NF1 patients without such deletions. All the patients were comprehensively characterized clinically and by echocardiography. Six of 16 NF1 deletion patients but none of 16 non-deletion NF1 patients have major cardiac abnormalities (p = 0.041). Congenital heart defects (CHDs) include mitral insufficiency in two patients and ventricular septal defect, aortic stenosis, and aortic insufficiency in one patient each. Three deletion patients have hypertrophic cardiomyopathy. Two patients have intracardiac tumors. NF1 patients without large deletions have increased left ventricular (LV) diastolic posterior wall thickness (p < 0.001) and increased intraventricular diastolic septal thickness (p = 0.001) compared with a healthy reference population without NF1, suggestive of eccentric LV hypertrophy. CHDs and other cardiovascular anomalies are more frequent among patients with large NF1 deletion and may cause serious clinical complications. Eccentric LV hypertrophy may occur in NF1 patients without whole gene deletions, but the clinical significance of this finding is uncertain. All patients with clinical suspicion for NF1 should be referred to a cardiologist for evaluation and surveillance.

Identification of Maillard reaction products on peanut allergens that influence binding to the receptor for advanced glycation end products.

BACKGROUND: Recent immunological data demonstrated that dendritic cells preferentially recognize advanced glycation end product (AGE)-modified proteins, upregulate expression of the receptor for AGE (RAGE), and consequently bias the immune response toward allergy. METHODS: Peanut extract was characterized by mass spectrometry (MS) to elucidate the specific residues and specific AGE modifications found in raw and roasted peanuts and on rAra h 1 that was artificially glycated by incubation with glucose or xylose. The binding of the RAGE-V1C1 domain to peanut allergens was assessed by PAGE and Western analysis with anti-Ara h 1, 2, and 3 antibodies. IgE binding to rAra h 1 was also assessed using the same methods. RESULTS: AGE modifications were found on Ara h 1 and Ara h 3 in both raw and roasted peanut extract. No AGE modifications were found on Ara h 2. Mass spectrometry and Western blot analysis demonstrated that RAGE binds selectively to Ara h 1 and Ara h 3 derived from peanut extract, whereas the analysis failed to demonstrate Ara h 2 binding to RAGE. rAra h 1 with no AGE modifications did not bind RAGE; however, after AGE modification with xylose, rAra h 1 bound to RAGE. CONCLUSIONS: AGE modifications to Ara h 1 and Ara h 3 can be found in both raw and roasted peanuts. Receptor for AGE was demonstrated to selectively interact with AGE-modified rAra h 1. If sensitization to peanut allergens occurs in dendritic cells via RAGE interactions, these cells are likely interacting with modified Ara h 1 and Ara h 3, but not Ara h 2.

The impact of regional deprivation and individual socio-economic status on the prevalence of Type 2 diabetes in Germany. A pooled analysis of five population-based studies.

AIM: Our objective was to test the hypothesis that the prevalence of Type 2 diabetes increases with increasing regional deprivation even after controlling for individual socio-economic status. METHODS: We pooled cross-sectional data from five German population-based studies. The data set contained information on n = 11,688 study participants (men 50.1%) aged 45-74 years, of whom 1008 people had prevalent Type 2 diabetes (men 56.2%). Logistic multilevel regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes prevalence. We controlled for sex, age and lifestyle risk factors, individual socio-economic status and regional deprivation, based on a new small-area deprivation measure, the German Index of Multiple Deprivation. RESULTS: Adjusted for sex, age, body mass index (BMI), physical activity, smoking status and alcohol consumption, the prevalence of Type 2 diabetes showed a stepwise increase in risk with increasing area deprivation [OR 1.88 (95% CI 1.16-3.04) in quintile 4 and OR 2.14 (95% CI 1.29-3.55) in quintile 5 compared with the least deprived quintile 1], even after controlling for individual socio-economic status. Focusing on individual socio-economic status alone, the risk of having diabetes was significantly higher for low compared with medium or high educational level [OR 1.46 (95% CI 1.24-1.71)] and for the lowest compared with the highest income group [OR 1.53 (95% CI 1.18-1.99)]. CONCLUSION: Regional deprivation plays a significant part in the explanation of diabetes prevalence in Germany independently of individual socio-economic status. The results of the present study could help to target public health measures in deprived regions.

Regional differences in the prevalence of known Type 2 diabetes mellitus in 45-74 years old individuals: results from six population-based studies in Germany (DIAB-CORE Consortium).

AIM: In Germany, regional data on the prevalence of Type 2 diabetes mellitus are lacking for health-care planning and detection of risk factors associated with this disease. We analysed regional variations in the prevalence of Type 2 diabetes and treatment with antidiabetic agents. METHODS: Data of subjects aged 45-74 years from five regional population-based studies and one nationwide study conducted between 1997 and 2006 were analysed. Information on self-reported diabetes, treatment, and diagnosis of diabetes were compared. Type 2 diabetes prevalence estimates (95% confidence interval) from regional studies were directly standardized to the German population (31 December 2007). RESULTS: Of the 11,688 participants of the regional studies, 1008 had known Type 2 diabetes, corresponding to a prevalence of 8.6% (8.1-9.1%). For the nationwide study, a prevalence of 8.2% (7.3-9.2%) was estimated. Prevalence was higher in men (9.7%; 8.9-10.4%) than in women (7.6%; 6.9-8.3%). The regional standardized prevalence was highest in the east with 12.0% (10.3-13.7%) and lowest in the south with 5.8% (4.9-6.7%). Among persons with Type 2 diabetes, treatment with oral antidiabetic agents was more frequently reported in the south (56.9%) and less in the northeast (46.0%), whereas treatment with insulin alone was more frequently reported in the northeast (21.6%) than in the south (16.4%). CONCLUSION: The prevalence of known Type 2 diabetes showed a southwest-to-northeast gradient within Germany, which is in accord with regional differences in the distribution of risk factors for Type 2 diabetes. Furthermore, the treatment with antidiabetic agents showed regional differences.

Correlation of heart rate at lactate minimum and maximal lactate steady state in wheelchair-racing athletes.

STUDY DESIGN: Prospective, experimental study. OBJECTIVE: To investigate whether the heart rate (HR) at lactate minimum (LMHR)determined by means of a HR-guided lactate minimum test (LMT) corresponds to the HR at maximal lactate steady state (MLSS) in wheelchair-racing athletes. SETTING: Institute of Sports Medicine. METHODS: Eight well-trained wheelchair-racing athletes (mean age: 33±12 years; height: 169±12 cm; body mass: 59±11 kg; VO(2peak): 2.76±0.73 l min(-1)) completed a HR-guided LMT on a treadmill in their own racing wheelchair. Subsequently, exercise intensity at MLSS and corresponding HR were determined by means of several endurance tests on different days. RESULTS: All measured parameters (HR, speed, blood lactate, oxygen consumption and rating of perceived exertion) revealed significantly higher values at MLSS compared with values at lactate minimum (LM). However, there were highly significant correlations (r=0.914, P=0.002) between LMHR and HR at MLSS (163±6 versus 172±7 b.p.m.) as well as for speed (r=0.935, P=0.001) and blood lactate (r=0.944, P<0.001) at LM versus MLSS. The correlation for oxygen consumption (r=0.798, P=0.018) at LM versus MLSS was lower yet significant. CONCLUSIONS: There exists a close relationship between LMHR and HR at MLSS in wheelchair racing. This allows the prediction of MLSS based on a single exercise test in this special group of athletes. For practical use during daily training, routine HR at MLSS can be assumed to be 8-9 b.p.m. above the LMHRin wheelchair-racing athletes.

International spinal cord injury pulmonary function basic data set.

OBJECTIVES: To develop the International Spinal Cord Injury (SCI) Pulmonary Function Basic Data Set within the framework of the International SCI Data Sets in order to facilitate consistent collection and reporting of basic bronchopulmonary findings in the SCI population. SETTING: International. METHODS: The SCI Pulmonary Function Data Set was developed by an international working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. RESULTS: The final International SCI Pulmonary Function Data Set contains questions on the pulmonary conditions diagnosed before spinal cord lesion,if available, to be obtained only once; smoking history; pulmonary complications and conditions after the spinal cord lesion, which may be collected at any time. These data include information on pneumonia, asthma, chronic obstructive pulmonary disease and sleep apnea. Current utilization of ventilator assistance including mechanical ventilation, diaphragmatic pacing, phrenic nerve stimulation and Bi-level positive airway pressure can be reported, as well as results from pulmonary function testing includes: forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk).

The impact of a fellow on a regional robotic-assisted partial nephrectomy service.

INTRODUCTION: Training a fellow has a cost in time and effort for the surgeon and their team. Their relative inexperience may also negatively affect the patient. The aim of this study was to determine and quantify the impact of a fellow on a regional robotic-assisted partial nephrectomy service and on perioperative outcomes. MATERIALS AND METHODS: We reviewed the prospectively collected data for 522 patients who had undergone robotic-assisted partial nephrectomy since 2015 during the tenure of six fellows. Perioperative outcomes for three groups were compared: group A (no fellow participation), group B (some participation) and group C (fellow completed entire operation). We also reviewed progression over 12 months. RESULTS: Demographics were similar in all groups apart from the percentage of men, which was lower in group C (p < 0.05). Operative time was 27 minutes longer for group B (p < 0.001). Warm ischaemia time was significantly shorter for group A but the difference was only four minutes (p < 0.001). Length of stay was slightly shorter for group C compared with the other groups (p < 0.01). Trifecta achievement was greatest for group A (p < 0.001). There were no perioperative deaths in any group and positive margins, complications and readmissions were low and similar in all groups. Towards the end of their fellowship, fellows performed more operations independently. CONCLUSION: There is a measurable, but small, negative impact of a fellow on a robotic-assisted partial nephrectomy service, which reduces with experience. With appropriate supervision and patient selection, a fellow can be taught robotic-assisted partial nephrectomy without affecting patient safety or treatment outcome.

Acute Lower Extremity Fracture Management in Chronic Spinal Cord Injury: 2022 Delphi Consensus Recommendations.

Our objective was to develop a clinical practice guideline (CPG) for the treatment of acute lower extremity fractures in persons with a chronic spinal cord injury (SCI). Methods: Information from a previous systematic review that addressed lower extremity fracture care in persons with an SCI as well as information from interviews of physical and occupational therapists, searches of the literature, and expert opinion were used to develop this CPG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to determine the quality of evidence and the strength of the recommendations. An overall GRADE quality rating was applied to the evidence. Conclusions: Individuals with a chronic SCI who sustain an acute lower extremity fracture should be provided with education regarding the risks and benefits of operative and nonoperative management, and shared decision-making for acute fracture management should be used. Nonoperative management historically has been the default preference; however, with the advent of greater patient independence, improved surgical techniques, and advanced therapeutics and rehabilitation, increased use of surgical management should be considered. Physical therapists, kinesiotherapists, and/or occupational therapists should assess equipment needs, skills training, and caregiver assistance due to changes in mobility resulting from a lower extremity fracture. Therapists should be involved in fracture management as soon as possible following fracture identification. Pressure injuries, compartment syndrome, heterotopic ossification, nonunion, malunion, thromboembolism, pain, and autonomic dysreflexia are fracture-related complications that clinicians caring for patients who have an SCI and a lower extremity fracture may encounter. Strategies for their treatment are discussed. The underlying goal is to return the patient as closely as possible to their pre-fracture functional level with operative or nonoperative management.

Near-field radiative heat transfer between macroscopic planar surfaces.

Near-field radiation allows heat to propagate across a small vacuum gap at rates several orders of magnitude above that of far-field, blackbody radiation. Although heat transfer via near-field effects has been discussed for many years, experimental verification of this theory has been very limited. We have measured the heat transfer between two macroscopic sapphire plates, finding an increase in agreement with expectations from theory. These experiments, conducted near 300 K, have measured the heat transfer as a function of separation over mm to µm and as a function of temperature differences between 2.5 and 30 K. The experiments demonstrate that evanescence can be put to work to transfer heat from an object without actually touching it.

Ara h 2: crystal structure and IgE binding distinguish two subpopulations of peanut allergic patients by epitope diversity.

BACKGROUND: Peanut allergy affects 1% of the population and causes the most fatal food-related anaphylactic reactions. The protein Ara h 2 is the most potent peanut allergen recognized by 80-90% of peanut allergic patients. METHODS: The crystal structure of the major peanut allergen Ara h 2 was determined for the first time at 2.7 Å resolution using a customized maltose-binding protein (MBP)-fusion system. IgE antibody binding to the MBP fusion construct vs the natural allergen was compared by ELISA using sera from peanut allergic patients. RESULTS: The structure of Ara h 2 is a five-helix bundle held together by four disulfide bonds and related to the prolamin protein superfamily. The fold is most similar to other amylase and trypsin inhibitors. The MBP--Ara h 2 fusion construct was positively recognized by IgE from 76% of allergic patients (25/33). Two populations of patients could be identified. Subpopulation 1 (n = 14) showed an excellent correlation of IgE antibody binding to natural vs recombinant Ara h 2. Subpopulation 2 (n = 15) showed significantly reduced IgE binding to the MBP fusion protein. Interestingly, about 20% of the IgE binding in subpopulation 2 could be recovered by increasing the distance between MBP and Ara h 2 in a second construct. DISCUSSION: The reduced IgE binding to the MBP--Ara h 2 of subpopulation 2 indicates that the MBP molecule protects an immunodominant epitope region near the first helix of Ara h 2. Residues involved in the epitope(s) are suggested by the crystal structure. The MBP--Ara h 2 fusion constructs will be useful to further elucidate the relevance of certain epitopes to peanut allergy.

Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.

Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations. Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration. Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. If this is true, then buffering intracellular energy levels could exert neuroprotective effects. Creatine kinase and its substrates creatine and phosphocreatine constitute an intricate cellular energy buffering and transport system connecting sites of energy production (mitochondria) with sites of energy consumption, and creatine administration stabilizes the mitochondrial creatine kinase and inhibits opening of the mitochondrial transition pore. We found that oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age. Creatine administration protected G93A transgenic mice from increases in biochemical indices of oxidative damage. Therefore, creatine administration may be a new therapeutic strategy for ALS.

Reliability of non-invasive cardiac output measurement in individuals with tetraplegia.

STUDY DESIGN: The study is conducted on the basis of comparative-repeated measures. OBJECTIVES: The objective of this study is to assess the reliability of non-invasive cardiac output (CO) measurements in individuals with tetraplegia (TP) at rest and during exercise using Innocor, and to test the hypothesis that CO measurements are less reliable in TP than in able-bodied (AB) individuals. SETTING: Ambulatory volunteers, Switzerland. METHODS: Nine male motor-complete TP (C5-C7) and nine pair-matched AB performed repeated CO measurements at rest and during submaximal arm-crank and wheelchair exercises in four different test sessions. Within- and between-day reliabilities were compared between TP and AB. RESULTS: Mean differences between measurements at rest (TP vs AB, within-day: 0.1±0.5 vs 0.2±0.6 l min(-1), between-day: -0.7±0.6 vs -0.1±0.8 l min(-1)), during arm-crank (TP vs AB, within-day: 0.1±0.9 vs 0.5±0.7 l min(-1), between-day: -0.3±1.1 vs 0.0±1.1 l min(-1)) and wheelchair exercises (TP vs AB, within-day: 0.3±1.2 vs -0.1±0.8 l min(-1), between-day: 0.1±1.1 vs 0.5±0.9 l min(-1)) were not significantly different between TP and AB (all P>0.05). Coefficients of variation in TP (within-day, rest: 6.8%, arm-crank: 9.6% and wheelchair: 10.8%; between-day, rest: 11.9%, arm-crank: 11.2% and wheelchair: 10.3%) and in AB (within-day, rest: 7.7%, arm crank: 6.8% and wheelchair: 6.0%; between-day, rest: 9.2%, arm crank: 8.5% and wheelchair: 8.0%) indicated acceptable reliability. CONCLUSION: In contrast to our hypothesis, we found non-invasive CO measurements using Innocor to be as reliable in TP as they are in AB. Consequently, Innocor can be recommended for repeated assessments of CO in TP within routine diagnostics or for evaluation of training progress.