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.

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.

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.

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.

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.

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.

Analysis of phasic and tonic electromyographic signal characteristics: electromyographic synthesis and comparison of novel morphological and linear-envelope approaches.

The pattern of tonic and phasic components in an EMG signal reflects the underlying behaviour of the central nervous system (CNS) in controlling the musculature. One avenue for gaining a better understanding of this behaviour is to seek a quantitative characterisation of these phasic and tonic components. We propose that these signal characteristics can range between unvarying, tonic and intermittent, phasic activation through a continuum of EMG amplitude modulation. In this paper, we present two new algorithms for quantifying amplitude modulation: a linear-envelope approach, and a mathematical morphology approach. In addition we present an algorithm for synthesising EMG signals with known amplitude modulation. The efficacy of the synthesis algorithm is demonstrated using real EMG data. We present an evaluation and comparison of the two algorithms for quantifying amplitude modulation based on synthetic data generated by the proposed synthesis algorithm. The results demonstrate that the EMG synthesis parameters represent 91.9% and 96.2% of the variance of linear-envelopes extracted from lumbo-pelvic muscle EMG signals collected from subjects performing a repetitive-movement task. This depended, however, on the muscle and movement-speed considered (F=4.02, p<0.001). Coefficients of determination between input and output amplitude modulation variables were used to quantify the accuracy of the linear-envelope and morphological signal processing algorithms. The linear-envelope algorithm exhibited higher coefficients of determination than the most accurate morphological approach (and hence greater accuracy, T=8.16, p<0.001). Similarly, the standard deviation of the coefficients of determination was 1.691 times smaller (p<0.001). This signal processing algorithm represents a novel tool for the quantification of amplitude modulation in continuous EMG signals and can be used in the study of CNS motor control of the musculature in repetitive-movement tasks.

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.

Altered response of the anterolateral abdominal muscles to simulated weight-bearing in subjects with low back pain.

An important aspect of neuromuscular control at the lumbo-pelvic region is stabilization. Subjects with low back pain (LBP) have been shown to exhibit impairments in motor control of key muscles which contribute to stabilization of the lumbo-pelvic region. However, a test of automatic recruitment that relates to function has been lacking. A previous study used ultrasound imaging to show that healthy subjects automatically recruited the transversus abdominis (TrA) and internal oblique (IO) muscles in response to a simulated weight-bearing task. This task has not been investigated in subjects with LBP. The aim of this study was to compare the automatic recruitment of the abdominal muscles among subjects with and without LBP in response to the simulated weight-bearing task. Twenty subjects with and without LBP were tested. Real-time ultrasound imaging was used to assess changes in thickness of the TrA and internal oblique IO muscles as well as lateral movement ("slide") of the anterior fascial insertion of the TrA muscle. Results showed that subjects with LBP showed significantly less shortening of the TrA muscle (P < 0.0001) and greater increases in thickness of the IO muscle (P = 0.002) with the simulated weight-bearing task. There was no significant difference between groups for changes in TrA muscle thickness (P = 0.055). This study provides evidence of changes in motor control of the abdominal muscles in subjects with LBP. This test may provide a functionally relevant and non-invasive method to investigate the automatic recruitment of the abdominal muscles in people with and without LBP.

Pelvic floor muscle activity in different sitting postures in continent and incontinent women.

OBJECTIVE: To determine whether resting activity of the pelvic floor muscles (PFMs) and abdominal muscles varied in different sitting postures in parous women with and without stress urinary incontinence (SUI). DESIGN: PFM and abdominal muscle activity was recorded in 3 sitting postures: slump supported, upright unsupported, and very tall unsupported. Spinal curves were measured in slump supported and upright unsupported. SETTING: A research laboratory. PARTICIPANTS: Women (N=17) with a history of vaginal delivery, 8 who were symptomatic of SUI and 9 who were asymptomatic. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Electromyographic activity of (1) the resting PFM recorded per vaginam with surface electrodes and (2) superficial abdominal muscles using surface electrodes. Changes in spinal curves were measured with a flexible ruler. RESULTS: Electromyographic activity of the PFM increased significantly from slump supported to upright unsupported postures in both groups (P<.001) but with lower levels of activity in women with SUI (P<.05). PFM activity increased further in very tall unsupported sitting in comparison with slump supported sitting (P<.001). Obliquus internus abdominis electromyographic activity was greater in upright unsupported than in slump supported sitting (P<.05), and electromyographic activity of other abdominal muscles was greater in very tall unsupported than slump supported. Women with SUI had a trend for greater activity in the abdominal muscles in upright unsupported than asymptomatic women. Asymptomatic women had a greater depth of lumbar lordosis in upright unsupported sitting than women with SUI (P=.04). CONCLUSIONS: More upright sitting postures recruit greater PFM resting activity irrespective of continence status. Further investigation should consider the effect of sitting posture in rehabilitation.

Effect of stabilization training on multifidus muscle cross-sectional area among young elite cricketers with low back pain.

STUDY DESIGN: A single-blinded, pretreatment-posttreatment assessment. OBJECTIVES: To investigate, using ultrasound imaging, the cross-sectional area (CSA) of the lumbar multifidus muscle at 4 vertebral levels (L2, L3, L4, L5) in elite cricketers with and without low back pain (LBP) and (2) to document the effect of a staged stabilization training program on multifidus muscle CSA. BACKGROUND: Despite high fitness levels and often intensive strength training programs, athletes still suffer LBP. The incidence of LBP among Australian cricketers is 8% and as high as 14% among fast bowlers. Previous researchers have found that the multifidus muscle contributes to segmental stability of the lumbopelvic region; however, the CSA of this muscle has not been previously assessed in elite cricketers. METHODS AND MEASURES: CSAs of the multifidus muscles were assessed at rest on the left and right sides for 4 vertebral levels at the start and completion of a 13-week cricket training camp. Participants who reported current or previous LBP were placed in a rehabilitation group. The stabilization program involved voluntary contraction of the multifidus, transversus abdominis, and pelvic floor muscles, with real-time feedback from rehabilitative ultrasound imaging (RUSI), progressed from non-weight-bearing to weight-bearing positions and movement training. Pain scores (using a visual analogue scale) were also collected from those with LBP. RESULTS: The CSAs of the multifidus muscles at the L5 vertebral level increased for the 7 cricketers with LBP who received the stabilization training, compared with the 14 cricketers without LBP who did not receive rehabilitation (P = .004). In addition, the amount of muscle asymmetry among those with LBP significantly decreased (P = .029) and became comparable to cricketers without LBP. These effects were not evident for the L2, L3, and L4 vertebral levels. There was also a 50% decrease in the mean reported pain level among the cricketers with LBP. CONCLUSION: Multifidus muscle atrophy can exist in highly active, elite athletes with LBP. Specific retraining resulted in an improvement in multifidus muscle CSA and this was concomitant with a decrease in pain. LEVEL OF EVIDENCE: Therapy, level 2b.

Tonic-to-phasic shift of lumbo-pelvic muscle activity during 8 weeks of bed rest and 6-months follow up.

Prior motor control studies in unloading have shown a tonic-to-phasic shift in muscle activation, particularly in the short extensors. Tonic muscle activity is considered critical for normal musculoskeletal function. The shift from tonic-to-phasic muscle activity has not been systematically studied in humans in unloading nor at the lumbo-pelvic (LP) region. Ten healthy young male subjects underwent 8 wk of bed rest with 6-mo follow up as part of the "Berlin Bed-Rest Study." A repetitive knee movement model performed in the prone position is used to stimulate tonic holding LP muscle activity, as measured by superficial EMG. Tonic and phasic activation patterns were quantified by relative height of burst vs. baseline electromyographic linear-envelope signal components. Statistical analysis shows a shift toward greater phasic activity during bed rest and follow up (P < 0.001) with a significant interaction across muscles (P < 0.001) specifically affecting the short lumbar extensors. These changes appear unrelated to skill acquisition over time (P all > or = 0.196). This change of a shift from tonic LP muscle activation to phasic is in line with prior research on the effects of reduced weight bearing on motor control.

Assessment of abdominal muscle function during a simulated unilateral weight-bearing task using ultrasound imaging.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To investigate the function of the transversus abdominis (TrA) and internal oblique (10) muscles bilaterally during a simulated weight-bearing task using ultrasound imaging. BACKGROUND: An important aspect of neuromuscular control at the lumbopelvic region is stabilization. Biomechanical models have predicted that activation of transversely oriented muscles, such as the TrA and 10 muscles, can stiffen the sacroiliac joints and actively stabilize the pelvis for weight bearing. METHODS AND MEASURES: Nineteen healthy subjects were positioned in supine lying with their right heel against a footplate linked to a force transducer. Each subject performed a static simulated weight-bearing task of the right lower extremity. Ultrasound imaging was used to assess resultant changes in thickness of the 10 and TrA muscles, as well as the lateral slide of the anterior abdominal fascia on each side of the abdomen alternately. Muscle thickness and slide of the fascia were assessed at standardized force levels (0% and 25% of body weight). RESULTS: Substantial increases (P < .0001) in mean (+/- SD) thickness of the 10 (18.5% +/- 9.7%) and TrA (24.7% +/- 175%) muscles during the weight-bearing task were measured. Lateral movement (slide) of the anterior abdominal fascia of the TrA muscle also occurred (mean +/- SD, 1.3 +/- 2.0 mm; P = .014) with weight bearing. Changes in muscle thickness and amount of slide were similar for the left and right side of the abdomen (P > or = .11). CONCLUSION: The findings are consistent with biomechanical models that predicted symmetrical activation of the deep transversely oriented lumbopelvic muscles in healthy subjects in response to a unilateral functional weight-bearing task. Ultrasound imaging as a measurement tool represents a noninvasive method for measuring abdominal muscle function in functional axial loading.

Ultrasound imaging assessment of abdominal muscle function during drawing-in of the abdominal wall: an intrarater reliability study.

STUDY DESIGN: Test-retest intrarater reliability study. OBJECTIVE: To examine reliability of abdominal musculature measurements across a broad range of conditions for a physical therapist newly trained in assessment using rehabilitative ultrasound imaging (RUSI). BACKGROUND: RUSI has previously been used to assess abdominal muscle function during a drawing-in maneuver of the anterior abdominal wall, and measurements conducted by an experienced assessor have been validated by comparison with magnetic resonance imaging. Few studies have examined the reliability of less experienced operators, and only in isolated measurement conditions. METHODS AND MEASURES: Nineteen subjects (11 female, 8 male) without a history of low back pain performed the abdominal drawing-in maneuver in a supine hook-lying position. RUSI was used bilaterally to assess the thickness of the internal oblique (IO) and transversus abdominis (TrA) muscles at rest and on contraction, as well as changes in the length of the TrA muscle (indicated by slide of the anterior abdominal fascia). The reliability of a novice rater who received 8 hours of training was examined (a) across 3 measurements of the same ultrasound image, (b) across 3 separate ultrasound images (averaged for days and sides of abdomen), and (c) across 2 days (averaged for images and sides). RESULTS: Reliability of assessing muscle thickness was very high across 3 measurements of the sale image (intrarater correlation coefficients [ICC3.1] were all greater than 0.97), fair to high across 3 images (ICC(3,4) = 0.62-0.82), and fair to high across 2 days (ICC(3,6) = 0.63-0.85). Reliability of measuring the slide of the anterior abdominal fascia was very high across measurements from the same image (ICC(3,1) = 0.98) but very low across images (ICC(3,4) = 0.44) and across 2 days (ICC(3,6) = 0.36). CONCLUSIONS: High reliability of a novice rater was demonstrated for some measurement conditions. Measures of reliability for recapturing the image and repetition across days ranged from low to high. Inconsistencies in the pattern of results suggest that for a novice assessor using RUSI, training should be performed and reliability assessed for each abdominal muscle and measurement condition intended to be used for research and clinical practice.

Sitting posture affects pelvic floor muscle activity in parous women: an observational study.

QUESTION: Do different sitting postures require different levels of pelvic floor and abdominal muscle activity in healthy women? DESIGN: Observational study. PARTICIPANTS: Eight parous women with no pelvic floor dysfunction. OUTCOME MEASURES: Bilateral activity of pelvic floor muscles (assessed vaginally) and two abdominal muscles, obliquus internus abdominis and obliquus externus abdominis, during three sitting postures. RESULTS: There was a significant increase in pelvic floor muscle activity from slump supported sitting (mean 7.2% maximal voluntary contraction, SD 4.8) to both upright unsupported sitting (mean 12.6% maximal voluntary contraction, SD 7.8) (p = 0.01) and very tall unsupported sitting (mean 24.3% maximal voluntary contraction, SD 14.2) (p = 0.004). Activity in both abdominal muscles also increased but did not reach statistical significance. CONCLUSION: Both unsupported sitting postures require greater pelvic floor muscle activity than the supported sitting posture.

The use of real-time ultrasound imaging for biofeedback of lumbar multifidus muscle contraction in healthy subjects.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To determine if the provision of visual biofeedback using real-time ultrasound imaging enhances the ability to activate the multifidus muscle. BACKGROUND: Increasingly clinicians are using real-time ultrasound as a form of biofeedback when re-educating muscle activation. The effectiveness of this form of biofeedback for the multifidus muscle has not been reported. METHODS AND MEASURES: Healthy subjects were randomly divided into groups that received different forms of biofeedback. All subjects received clinical instruction on how to activate the multifidus muscle isometrically prior to testing and verbal feedback regarding the amount of multifidus contraction, which occurred during 10 repetitions (acquisition phase). In addition, 1 group received visual biofeedback (watched the multifidus muscle contract) using real-time ultrasound imaging. All subjects were reassessed a week later (retention phase). RESULTS: Subjects from both groups improved their voluntary contraction of the multifidus muscle in the acquisition phase (P<.001) and the ability to recruit the multifidus muscle differed between groups (P<.05), with subjects in the group that received visual ultrasound biofeedback achieving greater improvements. In addition, the group that received visual ultrasound biofeedback retained their improvement in performance from week 1 to week 2 (P>.90), whereas the performance of the other group decreased (P<.05). CONCLUSION: Real-time ultrasound imaging can be used to provide visual biofeedback and improve performance and retention in the ability to activate the multifidus muscle in healthy subjects.

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.

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.