Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes.

AIMS: Morphological studies of pancreas samples obtained from young people with recent-onset type 1 diabetes have revealed distinct patterns of immune cell infiltration of the pancreatic islets suggestive of two age-associated type 1 diabetes endotypes that differ by inflammatory responses and rates of disease progression. The objective of this study was to investigate whether these proposed disease endotypes are associated with pathological differences in immune cell activation and cytokine secretion by applying multiplexed gene expression analysis to pancreatic tissue from recent-onset type 1 diabetes cases. METHODS: RNA was extracted from samples of fixed, paraffin-embedded pancreas tissue from type 1 diabetes cases characterised by endotype and from controls without diabetes. Expression levels of 750 genes associated with autoimmune inflammation were determined by hybridisation to a panel of capture and reporter probes and these were counted as a measure of gene expression. Normalised counts were analysed for differences in expression between 29 type 1 diabetes cases and 7 controls without diabetes, and between the two type 1 diabetes endotypes. RESULTS: Ten inflammation-associated genes, including INS, were significantly under-expressed in both endotypes and 48 genes were more highly expressed. A different set of 13 genes associated with the development, activation and migration of lymphocytes was uniquely overexpressed in the pancreas of people developing diabetes at younger age. CONCLUSIONS: The results provide evidence that histologically defined type 1 diabetes endotypes differ in their immunopathology and identify inflammatory pathways specifically involved in disease developing at a young age, essential for a better understanding of disease heterogeneity.

The Impact of Face-to-Face Pharmacist Transitional Care Management Visits on Medication-Related Problems.

Background: Studies are needed to evaluate medication-related problems (MRPs) to assess the effect of a pharmacist on managing medications postdischarge. Objective: To assess the ability of pharmacist-led medication review and reconciliation to reduce the number of MRPs found in transitional care medicine (TCM) visits, leading to medication optimization. Methods: This study involved a retrospective chart review of standard TCM procedure at a family/internal medicine clinic and a prospective, team-based TCM visit in the same clinic. Inclusion criteria included patients discharged from any hospital within our institution and seen in the clinic. The primary outcome was the difference in the proportion of MRPs found between the prospective and retrospective groups. Secondary outcomes included the number and specific type of MRPs found, classified by the Pharmaceutical Care Network Europe tool, and further subdivided by patient aware or unaware of MRP, only in the prospective group, as well as 30-day readmission rate. Results: Patients in the prospective group (n = 50) had an average age of 67.9 years versus 65.5 years in the retrospective group (n = 50). Four times as many patients in the prospective group were found to have MRPs than the retrospective group. The most common MRP was due to a patient-related factor, meaning the cause is related to a patient's behavior. Patients were unaware of the MRP in a majority of these cases. Thirty-day readmission rate did not differ between the groups. Conclusion: Team-based TCM visits that included a pharmacist-led medication reconciliation uncovered more MRPs than patients who did not have a pharmacist perform a medication reconciliation.

Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas.

STUDY OBJECTIVE: To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. DESIGN: Retrospective chart review. SETTING: Large integrated health system. PATIENTS: A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard-infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended-infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). CONCLUSION: Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed to the triple premedication regimen received more frequently in patients in the extended-infusion group.

Identification of Tetraspanin-7 as a Target of Autoantibodies in Type 1 Diabetes.

The presence of autoantibodies to multiple-islet autoantigens confers high risk for the development of type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA2, and zinc transporter-8), but the molecular identity of a fifth, a 38-kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography, and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from the sera of patients with diabetes before SDS-PAGE. Eluates from gel regions equivalent to 38 kDa were analyzed by liquid chromatography-tandem mass spectrometry for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity-purified sample, but not in the negative control. Only tetraspanin-7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy.

Activation of the hip adductor muscles varies during a simulated weight-bearing task.

OBJECTIVE: To investigate the pattern of muscle activation of the individual hip adductor muscles using a standardised simulated unilateral weight-bearing task. DESIGN: A repeated measures design. SETTING: Laboratory. PARTICIPANTS: 20 healthy individuals (11 females, 9 males) participated in the study. Age ranged from 20 to 25 years. MAIN OUTCOME MEASUREMENTS: Surface electromyography recordings from adductor magnus and adductor longus muscles were taken at levels representing 10-50% of body weight during a simulated weight-bearing task. Electromyography (EMG) data were normalised to maximal voluntary isometric contraction. RESULTS: The adductor magnus was recruited at significantly higher levels than the adductor longus muscle during a simulated weight-bearing task performed across 10-50% of body weight (p < 0.01). CONCLUSIONS: Adductor magnus and adductor longus muscles are recruited to different extents during a simulated weight-bearing task. This information should be considered when selecting exercises for management and prevention of groin strains. Closed chain exercises with weight-bearing through the lower limb are more likely to recruit the adductor magnus muscle over the adductor longus muscle.

Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes.

AIMS/HYPOTHESIS: Insulinoma-associated protein 2 (IA-2) is a major target of autoimmunity in type 1 diabetes. When first detected, IA-2-autoantibodies commonly bind epitopes in the juxtamembrane (JM) domain of IA-2 and antibody responses subsequently spread to the tyrosine phosphatase domain. Definition of structures of epitopes in the JM domain, and genetic requirements for autoimmunity to these epitopes, is important for our understanding of initiation and progression of autoimmunity. The aims of this study were to investigate the contribution of individual amino acids in the IA-2 JM domain to antibody binding to these epitopes and the role of HLA genotypes in determining epitope specificity. METHODS: Regions of the JM domain recognised by autoantibodies were identified by peptide competition and inhibitory effects of alanine substitutions of residues within the JM region. Antibody binding was determined by radioligand binding assays using sera from patients genotyped for HLA-DRB1 and -DQB1 alleles. RESULTS: Patients were categorised into two distinct groups of JM antibody reactivity according to peptide inhibition. Inhibition by substitutions of individual amino acids within the JM domain differed between patients, indicating heterogeneity in epitope recognition. Cluster analysis defined six groups of residues having similar inhibitory effects on antibody binding, with three clusters showing differences in patients affected or unaffected by peptide. One cluster demonstrated significant differences in antibody binding between HLA-DRB1*04 and HLA-DRB1*07 patients and within DRB1*04 individuals; antibody recognition of a second cluster depended on expression of HLA-DQB1*0302. CONCLUSIONS/INTERPRETATION: The results identify amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity.

Hybrid (CT/MRI based) vs. MRI only based image-guided brachytherapy in cervical cancer: Dosimetry comparisons and clinical outcome.

PURPOSE: Limited access to MRI has restricted implementation of MRI-based image-guided brachytherapy (IGBT) in line with GEC-ESTRO guidelines in many centers. This work reports our experience using an alternative CT/MRI based (hybrid) approach for IGBT, dosimetry comparisons, and its impact on long-term clinical outcome and major toxicity. METHODS AND MATERIALS: Seventy-six patients diagnosed with locally advanced cervical cancer between May 2008 and May 2012 treated with IGBT were analyzed. The hybrid approach is the default IGBT approach during this study period. Forty-nine had hybrid approach and 27 patients had "3-fraction conformal MRI" approach (17 within EMBRACE study). Treatment consisted of 48 Gy in 24 fractions of conformally planned external beam radiotherapy with weekly cisplatin followed by three weekly fractions of brachytherapy to high-risk clinical target volume (HR-CTV). All patients have a prebrachytherapy MRI 4 days before treatment and with the applicators in place on Fraction 1. MRI only or CT is used for subsequent fractions. Using image registration techniques and the assumption that the HR-CTV is fixed with respect to the applicator, the HR-CTV from MRI at Fraction 1 is transferred onto subsequent fraction CT image sets for the hybrid approach. RESULTS: Median follow-up was 41 months (range, 23-71 months). Excellent 3-year local control, overall progression-free survival, and overall survival of 92.6%, 78.8%, and 77.7% were seen with the hybrid approach and 92.2%, 66.3%, and 69.6% with a 3-fraction conformal MRI approach, respectively. Dosimetry achieved and late toxicity rates were comparable in the two groups. CONCLUSIONS: Hybrid IGBT in locally advanced cervical cancer offers an alternative approach when access to MRI restricts implementation of IGBT.

Low Back Pain in Microgravity and Bed Rest Studies.

BACKGROUND: The prevalence of low back pain (LBP) for astronauts in space (68%) is higher than the 1-mo prevalence for the general population on Earth (39%). It is unclear whether differences occur between healthy subjects and astronauts with a history of LBP. Knowledge of this issue is important to assess whether a history of LBP could have an operational impact. METHODS: We evaluated LBP prospectively during short duration spaceflight (15 d; N=20) and compared this with similar data collected during two bed rest studies (N=40). Astronauts completed a questionnaire 5-10 d preflight, during each flight day, and 5-10 d postflight. RESULTS: All astronauts with a history of LBP also developed LBP in flight. These astronauts reported a significantly longer duration of LBP and a different pain location. LBP was most often experienced in the central area of the lower back during spaceflight with an incidence of 70% and a mean pain level of 3 (on a scale of 0-10). Pain resolved within 10 d of flight. No neurological signs were present. The most frequently reported countermeasure was assuming a "knees to chest (fetal tuck) position" combined with stretching. Greater LBP intensity was reported in spaceflight than bed rest with a trend indicating a greater number of days of pain during spaceflight. DISCUSSION: The current study represents a prospective study of LBP in spaceflight. The results indicate that LBP is self-limiting in spaceflight and should not pose an operational risk. Prior LBP on Earth appears to be a risk factor for LBP in spaceflight.

Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: Implications for determinant spreading.

Diversification of autoimmunity to islet autoantigens is critical for progression to Type 1 diabetes. B-cells participate in diversification by modifying antigen processing, thereby influencing which peptides are presented to T-cells. In Type 1 diabetes, JM antibodies are associated with T-cell responses to PTP domain peptides. We investigated whether this is the consequence of close structural alignment of JM and PTP domain determinants on IA-2. Fab fragments of IA-2 antibodies with epitopes mapped to the JM domain blocked IA-2 binding of antibodies that recognise epitopes in the IA-2 PTP domain. Peptides from both the JM and PTP domains were protected from degradation during proteolysis of JM antibody:IA-2 complexes and included those representing major T-cell determinants in Type 1 diabetes. The results demonstrate close structural relationships between JM and PTP domain epitopes on IA-2. Stabilisation of PTP domain peptides during proteolysis in JM-specific B-cells may explain determinant spreading in IA-2 autoimmunity.

HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

Autoantibodies to IA-2 in type 1 diabetes are associated with HLA-DR4, suggesting influences of HLA-DR4-restricted T cells on IA-2-specific B cell responses. The aim of this study was to investigate possible T-B cell collaboration by determining whether autoantibodies to IA-2 epitopes are associated with T cell responses to IA-2 peptides presented by DR4. T cells secreting the cytokines IFN-γ and IL-10 in response to seven peptides known to elicit T cell responses in type 1 diabetes were quantified by cytokine ELISPOT in HLA-typed patients characterized for Abs to IA-2 epitopes. T cell responses were detected to all peptides tested, but only IL-10 responses to 841-860 and 853-872 peptides were associated with DR4. Phenotyping by RT-PCR of FACS-sorted CD45RO(hi) T cells secreting IL-10 in response to these two peptides indicated that these expressed GATA-3 or T-bet, but not FOXP3, consistent with these being Th2 or Th1 memory T cells rather than of regulatory phenotype. T cell responses to the same two peptides were also associated with specific Abs: those to 841-860 peptide with Abs to juxtamembrane epitopes, which appear early in prediabetes, and those to peptide 853-872 with Abs to an epitope located in the 831-862 central region of the IA-2 tyrosine phosphatase domain. Abs to juxtamembrane and central region constructs were both DR4 associated. This study identifies a region of focus for B and T cell responses to IA-2 in HLA-DR4 diabetic patients that may explain HLA associations of IA-2 autoantibodies, and this region may provide a target for future immune intervention to prevent disease.

Assessment of uterus position as a surrogate for high-risk clinical target volume with respect to the applicator position for multiple fractions of brachytherapy in cervical cancer.

AIM: Hybrid magnetic resonance imaging/computerized tomography (MRI/CT) planning for high-dose-rate (HDR) brachytherapy in cervical cancer with MR/CT fusion for the first fraction followed by CT for fraction 2 and 3 is used at our center. The aim of this study is to evaluate the position of applicator intrauterine tube (IU) in relation to uterine serosa with each fraction of intracavitary high-dose-rate brachytherapy. METHODS: Position of the applicator relative to uterus was measured from tip of the applicator (IU) to the top of uterus in the plane of IU and perpendicular to IU in anterior, posterior, left and right directions at the tip of IU, mid-point of the IU and 1 cm from the surface of vaginal ring. The mean absolute difference (±95 % confidence interval) between these positions at fraction 2 and 3 was calculated with fraction one as reference. RESULTS: The mean absolute difference (±95 %) of the applicator relative to uterus was 2.7 ± 0.5 mm at the tip, 1.5 ± 4 mm at mid-point and 1.1 ± 0.3 mm at 1 cm from the surface of the ring. CONCLUSION: This study shows that there is consistency in inter-fraction applicator position relative to uterus apart from at the tip and, therefore, in situations where high-risk clinical target volume (HRCTV) extends towards uterine fundus, MRI should be used for each fraction of brachytherapy planning to accurately define HRCTV.

Failure to detect anti-idiotypic antibodies in the autoimmune response to IA-2 in Type 1 diabetes.

The concept that immune responses to self antigens are regulated by anti-idiotypic networks has attracted renewed interest following reports of circulating factors within IgG fractions of serum that impair detection of autoantibodies with autoantigen. Thus, preclearance of sera with bead-immobilised monoclonal autoantibodies to the Type 1 diabetes autoantigen GAD65, or prebinding of serum antibodies to protein A Sepharose prior to addition of antigen, increases immunoreactivity detected in serum samples consistent with the trapping on the beads of anti-idiotypic antibodies that block antibody binding to the autoantigen. The aim of this study was to investigate the presence of anti-idiotypic antibodies to another major target of autoantibodies in Type 1 diabetes, IA-2. As previously observed for GAD65, preadsorption of serum samples with immobilised monoclonal IA-2 autoantibody, or prebinding to protein A Sepharose, resulted in substantial increases in subsequent immunoprecipitation of radiolabeled IA-2 in a proportion of samples. However, control experiments indicated that the increases seen on pre-incubation with immobilized autoantibodies were caused by displacement of the antibody by serum IgG, whereas impaired detection of immunoreactivity in liquid-phase radiobinding assays was the result of formation of insoluble complexes that bind poorly to protein A. The results emphasise the importance of direct demonstration of specific binding of antibodies to the idiotype in the study of idiotypic networks in autoimmunity. Variability between patients in formation of insoluble immune complexes has implications for the design and standardization of autoantibody assays for diabetes prediction.

Resistive vibration exercise during bed-rest reduces motor control changes in the lumbo-pelvic musculature.

To understand the effects of a resistive vibration exercise (RVE) countermeasure on changes in lumbo-pelvic muscle motor control during prolonged bed-rest, 20 male subjects took part in the Berlin Bed-Rest Study (in 2003-2005) and were randomised to a RVE group or an inactive control group. Surface electromyographic signals recorded from five superficial lumbo-pelvic muscles during a repetitive knee movement task. The task, which required stabilisation of the lumbo-pelvic region, was performed at multiple movement speeds and at multiple time points during and after bed-rest. After excluding effects that could be attributed to increases in subcutaneous fat changes and improvements in movement skill, we found that the RVE intervention ameliorated the generalised increases in activity ratios between movement speeds (p⩽0.012), reductions in lumbo-pelvic extensor and flexor co-contraction (p=0.058) and increases in root-mean-square electromyographic amplitude (p=0.001) of the lumbar erector spinae muscles. Effects of RVE on preventing increases in amplitude-modulation (p=0.23) of the lumbar erector spinae muscles were not significant. Few significant changes in activation-timing were seen. The RVE intervention during bed-rest, with indirect loading of the spine during exercise, was capable of reducing some, but not all, motor control changes in the lumbo-pelvic musculature during and after bed-rest.

The effects of rehabilitation on the muscles of the trunk following prolonged bed rest.

Microgravity and inactivity due to prolonged bed rest have been shown to result in atrophy of spinal extensor muscles such as the multifidus, and either no atrophy or hypertrophy of flexor muscles such as the abdominal group and psoas muscle. These effects are long-lasting after bed rest and the potential effects of rehabilitation are unknown. This two-group intervention study aimed to investigate the effects of two rehabilitation programs on the recovery of lumbo-pelvic musculature following prolonged bed rest. 24 subjects underwent 60 days of head down tilt bed rest as part of the 2nd Berlin BedRest Study (BBR2-2). After bed rest, they underwent one of two exercise programs, trunk flexor and general strength (TFS) training or specific motor control (SMC) training. Magnetic resonance imaging of the lumbo-pelvic region was conducted at the start and end of bed rest and during the recovery period (14 and 90 days after re-ambulation). Cross-sectional areas (CSAs) of the multifidus, psoas, lumbar erector spinae and quadratus lumborum muscles were measured from L1 to L5. Morphological changes including disc volume, spinal length, lordosis angle and disc height were also measured. Both exercise programs restored the multifidus muscle to pre-bed-rest size, but further increases in psoas muscle size were seen in the TFS group up to 14 days after bed rest. There was no significant difference in the number of low back pain reports for the two rehabilitation groups (p=.59). The TFS program resulted in greater decreases in disc volume and anterior disc height. The SMC training program may be preferable to TFS training after bed rest as it restored the CSA of the multifidus muscle without generating potentially harmful compressive forces through the spine.

Muscle atrophy and changes in spinal morphology: is the lumbar spine vulnerable after prolonged bed-rest?

STUDY DESIGN: prospective longitudinal study. OBJECTIVE: to evaluate the effect of bed-rest on the lumbar musculature and soft-tissues. SUMMARY OF BACKGROUND DATA: earlier work has suggested that the risk of low back injury is higher after overnight bed-rest or spaceflight. Changes in spinal morphology and atrophy in musculature important in stabilizing the spine could be responsible for this, but there are limited data on how the lumbar musculature and vertebral structures are affected during bed-rest. METHODS: nine male subjects underwent 60-days head-down tilt bed-rest as part of the second Berlin Bed-Rest Study. Disc volume, intervertebral spinal length, intervertebral lordosis angle, and disc height were measured on sagittal plane magnetic resonance images. Axial magnetic resonance images were used to measure cross-sectional areas (CSAs) of the multifidus (MF), erector spinae, quadratus lumborum, and psoas from L1 to L5. Subjects completed low back pain (LBP) questionnaires for the first 7-days after bed-rest. RESULTS: increases in disc volume, spinal length (greatest at lower lumbar spine), loss of the lower lumbar lordosis, and move to a more lordotic position at the upper lumbar spine (P < 0.0097) were seen. The CSAs of all muscles changed (P < 0.002), with the rate of atrophy greatest at L4 and L5 in MF (P < 0.002) and at L1 and L2 in the erector spinae (P = 0.0006). Atrophy of the quadratus lumborum was consistent throughout the muscle (P = 0.15), but CSA of psoas muscle increased (P < 0.0001). Subjects who reported LBP after bed-rest showed, before reambulation, greater increases in posterior disc height, and greater losses of MF CSA at L4 and L5 than subjects who did not report pain (all P < 0.085). CONCLUSION: these results provide evidence that changes in the lumbar discs during bed-rest and selective atrophy of the MF muscle may be important factors in the occurrence of LBP after prolonged bed-rest.

Countermeasures against lumbar spine deconditioning in prolonged bed rest: resistive exercise with and without whole body vibration.

To evaluate the effect of short-duration, high-load resistive exercise, with and without whole body vibration on lumbar muscle size, intervertebral disk and spinal morphology changes, and low back pain (LBP) incidence during prolonged bed rest, 24 subjects underwent 60 days of head-down tilt bed rest and performed either resistive vibration exercise (n = 7), resistive exercise only (n = 8), or no exercise (n = 9; 2nd Berlin Bed-Rest Study). Discal and spinal shape was measured from sagittal plane magnetic resonance images. Cross-sectional areas (CSAs) of the multifidus, erector spinae, quadratus lumborum, and psoas were measured on para-axial magnetic resonance images. LBP incidence was assessed with questionnaires at regular intervals. The countermeasures reduced CSA loss in the multifidus, lumbar erector spinae and quadratus lumborum muscles, with greater increases in psoas muscle CSA seen in the countermeasure groups (P ≤ 0.004). There was little statistical evidence for an additional effect of whole body vibration above resistive exercise alone on these muscle changes. Exercise subjects reported LBP more frequently in the first week of bed rest, but this was only significant in resistive exercise only (P = 0.011 vs. control, resistive vibration exercise vs. control: P = 0.56). No effect of the countermeasures on changes in spinal morphology was seen (P ≥ 0.22). The results suggest that high-load resistive exercise, with or without whole body vibration, performed 3 days/wk can reduce lumbar muscle atrophy, but further countermeasure optimization is required.

Influence of prolonged bed-rest on spectral and temporal electromyographic motor control characteristics of the superficial lumbo-pelvic musculature.

Little is known about the motor control of the lumbo-pelvic musculature in microgravity and its simulation (bed-rest). Analysis of spectral and temporal electromyographic variables can provide information on motor control relevant for normal function. This study examined the effect of 56-days of bed-rest with 1-year follow-up in 10 male subjects on the median frequency and the activation timing in surface electromyographic recordings from five superficial lumbo-pelvic muscles during a repetitive knee movement task. Trunk fat mass (from whole body-composition measurements) and movement accuracy as possible explanatory factors were included. Increased median frequency was observed in the lumbar erector spinae starting late in bed-rest, but this was not seen in its synergist, the thoracic erector spinae (p<.0001). These changes persisted up to 1-year after bed-rest and were independent of changes in body-composition or movement accuracy. Analysis suggested decreases of median frequency (p<.0001) in the abdominal and gluteal muscles to result from increased (p<.01) trunk fat levels during and after bed-rest. No changes in lumbo-pelvic muscle activation timing were seen. The results suggest that bed-rest particularly affects the shorter lumbar erector spinae and that the temporal sequencing of superficial lumbo-pelvic muscle activation is relatively robust.

Effect of prolonged bed rest on the anterior hip muscles.

Prolonged bed rest and inactivity is known to cause muscular atrophy with previous research indicating that muscles involved in joint stabilisation are more susceptible. The anterior hip muscles are important for hip joint function and stability but little is known about the effects of prolonged inactivity on their function. This study investigated the effect of prolonged bed rest on the size of the anterior hip muscles and their pattern of recovery. The effect of resistive vibration exercise (RVE) as a countermeasure to muscle atrophy was also investigated. 12 male participants, randomly assigned to either a control or an exercise group, underwent 8 weeks of bed rest with 6 months follow-up. Changes in muscle cross-sectional area (CSA) of the iliacus, psoas, iliopsoas, sartorius and rectus femoris muscles were measured by magnetic resonance imaging at regular intervals during bed rest and recovery phases. CSAs of iliopsoas and sartorius decreased at the hip joint (p<0.05) during bed rest but iliacus, psoas, and rectus femoris CSAs were unchanged (p>0.05). No significant difference was found between the two groups for all muscles (all p>0.1), suggesting inefficacy of the countermeasure in this sample. These findings suggest that prolonged bed rest can result in the atrophy of specific muscles across the hip joint which may affect its stability and function.

Differential atrophy of the lower-limb musculature during prolonged bed-rest.

Patients with medical, orthopaedic and surgical conditions are often assigned to bed-rest and/or immobilised in orthopaedic devices. Although such conditions lead to muscle atrophy, no studies have yet considered differential atrophy of the lower-limb musculature during inactivity to enable the development of rehabilitative exercise programmes. Bed-rest is a model used to simulate the effects of spaceflight and physical inactivity. Ten male subjects underwent 56-days of bed-rest. Magnetic resonance imaging of the lower-limbs was performed at 2-weekly intervals during bed-rest. Volume of individual muscles of the lower-limb and subsequently, rates of atrophy were calculated. Rates of atrophy differed (F = 7.4, p < 0.0001) between the muscles with the greatest rates of atrophy seen in the medial gastrocnemius, soleus and vastii (p < 0.00000002). The hamstring muscles were also affected (p < 0.00015). Atrophy was less in the ankle dorsiflexors and anteromedial hip muscles (p > 0.081). Differential rates of atrophy were seen in synergistic muscles (e.g. adductor magnus > adductor longus, p = 0.009; medial gastrocnemius > lateral gastrocnemius, p = 0.002; vastii > rectus femoris, p = 0.0002). These results demonstrate that muscle imbalances can occur after extended periods of reduced postural muscle activity, potentially hampering recovery on return to full upright body position. Such deconditioned patients should be prescribed "closed-chain" simulated resistance exercises, which target the lower-limb antigravity extensor muscles which were most affected in bed-rest.