Validation of a handheld near-infrared spectrophotometer for measurement of chemical intramuscular fat in Australian lamb.

The objective of the study was to independently validate a calibrated commercial handheld near infrared (NIR) spectroscopic device and test its repeatability over time using phenotypically diverse populations of Australian lamb. Validation testing in eight separate data sub-groups (n = 1591 carcasses overall) demonstrated that the NIR device had moderate precision (R2 = 0.4-0.64, RMSEP = 0.70-1.22%) but fluctuated in accuracy between experimental site demonstrated by variable slopes (0.50-0.94) and biases (-0.86-0.02). The repeatability experiment (n = 10 carcasses) showed that time to scan post quartering affected NIR measurement from 0 to 24 h (P < 0.001). On average, NIR IMF% was 0.97% lower (P < 0.001) at 24 h (4.01% ± 0.166), compared to 0 h. There was no difference (P > 0.05) between Time 0 and 1 h or Time 0 and 4 h or between replicate scans within each time point. This study demonstrated the SOMA NIR device could predict lamb chemical IMF% with moderate precision and accuracy, however additional work is required to understand how loin preparation, blooming and surface hydration affect NIR measurement.

The effect of laryngeal elevation training on swallowing function in patients with dysphagia.

OBJECTIVE: To investigate the effect of laryngeal elevation training without highly loaded head lifting on swallowing function in patients with dysphagia. METHODS: Fifty-seven patients with dysphagia (36 men; mean age, 78.5 ± 11.4 years) were included. All participants performed the swallowing forehead exercise and the chin push-pull manoeuvre for two months. Videoendoscopy to assess swallowing function, the peak expiratory flow test and the hand grip strength test were performed at the initial visit (time 1) and two months after the start of the intervention (time 2). We used the Hyodo score, a scoring method for videoendoscopic assessment, for evaluation of swallowing function. RESULTS: The linear mixed model showed a significant main effect of time (the Hyodo score at time 1 was greater than the score at time 2). The effects of the co-variates were not significant. CONCLUSION: The present study demonstrated the significant effect of laryngeal elevation training without head lifting on the Hyodo score.

Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.

Correction to: Differences in bone quality and strength between Asian and Caucasian young men.

The second name of the ninth author, X.E. Guo, was incorrectly coded as part of his surname. The publisher apologises for the inconvenience caused.

Abnormal microarchitecture and stiffness in postmenopausal women using chronic inhaled glucocorticoids.

Postmenopausal (PM) women using inhaled glucocorticoids (IGCs) had substantial abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness using high resolution peripheral computed tomography (HRpQCT) compared to age- and race-matched controls. Abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs. INTRODUCTION: While oral glucocorticoids are well recognized to have destructive skeletal effects, less is known about the effects of IGCs. The detrimental skeletal effects of IGCs may be greatest in PM women, in whom they compound negative effects of estrogen loss and aging. The goal of this study was to evaluate microarchitecture and stiffness in PM women using chronic IGCs. METHODS: This case-control study compared PM women using IGCs for ≥ 6 months (n = 20) and controls matched for age and race/ethnicity (n = 60). Skeletal parameters assessed included areal BMD (aBMD) by DXA, trabecular and cortical vBMD and microarchitecture by HRpQCT of the radius and tibia, and whole bone stiffness by finite element analysis. RESULTS: By DXA, mean values in both groups were in the osteopenic range; hip aBMD was lower in IGC users (P < 0.04). By HRpQCT, IGC users had lower total, cortical, and trabecular vBMD at both radius and tibia (all P < 0.05). IGC users had lower cortical thickness, lower trabecular number, greater trabecular separation and heterogeneity at the radius (all P < 0.03), and greater heterogeneity at the tibia (P < 0.04). Whole bone stiffness was lower in IGC users at radius (P < 0.03) and tended to be lower at the tibia (P = 0.09). CONCLUSIONS: PM women using IGCs had substantial abnormalities in vBMD, microarchitecture, and stiffness compared to controls. These abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs.

Bone density and microarchitecture in hepatitis C and HIV-coinfected postmenopausal minority women.

We found that HIV+/HCV+ women had 7-8% lower areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) at the spine, hip, and radius (p < 0.01) and 5-7% lower volumetric BMD (vBMD) by central quantitative computed tomography (cQCT) at the spine and hip (p < 0.05). These data suggest that true deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women. INTRODUCTION: aBMD by DXA is lower in persons coinfected with HIV and HCV (HIV+/HCV+) than with HIV monoinfection (HIV+). However, weight is often also lower with HCV infection, and measurement of aBMD by DXA can be confounded by adiposity; we aimed to determine whether true vBMD is also lower in HIV+/HCV+ coinfection. METHODS: We measured aBMD of the lumbar spine (LS), total hip (TH), femoral neck (FN), and ultradistal radius (UDR) by DXA and vBMD of the spine and hip by cQCT and of the distal radius and tibia by high-resolution peripheral QCT (HRpQCT) in 37 HIV+/HCV+ and 119 HIV+ postmenopausal women. Groups were compared using Student's t tests with covariate adjustment by multiple regression analysis. RESULTS: HIV+/HCV+ and HIV+ women were of similar age and race/ethnicity. HIV+/HCV+ women had lower body mass index (BMI) and trunk fat and were more likely to smoke and less likely to have a history of AIDS. In HIV+/HCV+ women, aBMD by DXA was 7-8% lower at the LS, TH, and UDR (p < 0.01). Similarly, vBMD by cQCT was 5-7% lower at the LS and TH (p < 0.05). Between-group differences in LS aBMD and vBMD remained significant after adjustment for BMI, smoking, and AIDS history. Tibial total vBMD by HRpQCT was 10% lower in HIV+/HCV+ women. CONCLUSION: HIV+/HCV+ postmenopausal women had significantly lower spine aBMD and vBMD. These deficits in vBMD may contribute to bone fragility and excess fractures reported in HIV+/HCV+ women.

Cortical microstructure compensates for smaller bone size in young Caribbean Hispanic versus non-Hispanic white men.

Hispanic men have smaller bone size but thicker and denser cortices compared to white men, leading to similar mechanical competence. INTRODUCTION: The purpose of this study was to assess differences in vBMD and microarchitecture in young Caribbean Hispanic (n = 30) and non-Hispanic Caucasian (n = 30) men. METHODS: We measured areal bone mineral density (aBMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual-energy X-ray absorptiometry (DXA) and bone geometry, mass, microarchitecture, and mechanical competence by high-resolution peripheral quantitative computed tomography (HRpQCT), individual trabecula segmentation (ITS), and finite element analysis (FEA). RESULTS: Hispanic men were slightly older, shorter, and heavier and had higher BMI compared with white men. aBMD, measured by DXA, did not differ at the spine, TH, or forearm before or after adjustment for age, height, weight, and the interaction of height and weight. At the FN, marginally significant higher BMD in Hispanics prior to adjustment was attenuated and no longer differed after adjustment for covariates. Adjusted HRpQCT indices indicated smaller total and trabecular area at the radius but greater total volumetric density and cortical thickness in Hispanic versus white men. The adjusted difference in cortical density at the radius was of borderline significance. Trabecular and ITS microstructure tended not to differ at the radius. At the tibia, results were similar. Bone size tended to be smaller and covariate-adjusted cortical density and cortical thickness were greater in Hispanic versus white men. Additionally, cortical porosity was lower at the tibia in Hispanic compared to white men. Stiffness and failure load did not differ at either skeletal site by ethnicity. CONCLUSION: In conclusion, greater cortical thickness and density as well as lower cortical porosity tend to compensate for smaller bone size in Hispanic men, leading to similar mechanical competence compared with white men.

Differences in bone quality and strength between Asian and Caucasian young men.

This is a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. We found that Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but stiffness did not differ between groups. INTRODUCTION: We conducted a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. METHODS: We measured bone mineral density (BMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual energy X-ray absorptiometry (DXA), and bone geometry, density, microarchitecture, and mechanical competence at the radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) with application of individual trabecula segmentation (ITS) and trabecular and whole bone finite element analysis (FEA). We measured load-to-strength ratio to account for differences in bone size and height, respectively. We used Wilcoxon rank sum and generalized linear models adjusted for height, weight, and their interaction for comparisons. RESULTS: Asians were 3.9 % shorter and weighed 6.5 % less than Caucasians. In adjusted models: by DXA, there were no significant race-based differences in areal BMD; by HR-pQCT, at the radius, Asians had smaller total and trabecular area (p = 0.003 for both), and denser (p = 0.01) and thicker (p = 0.04) cortices at the radius; by ITS, at the radius Asians, had more plate-like than rod-like trabeculae (PR ratio p = 0.01), greater plate trabecular surface (p = 0.009) and longer rod length (p = 0.002). There were no significant race-based differences in FEA or the load-to-strength ratio. CONCLUSIONS: Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but biomechanical estimates of bone strength did not differ between groups. Studies are needed to determine whether these differences persist later in life.

Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training.

In this study, we determined that operator positioning precision contributes significant measurement error in high-resolution peripheral quantitative computed tomography (HR-pQCT). Moreover, we developed software to quantify intra- and inter-operator variability and demonstrated that standard positioning training (now available as a web-based application) can significantly reduce inter-operator variability. INTRODUCTION: HR-pQCT is increasingly used to assess bone quality, fracture risk, and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection ("scout view image") and define the region to be scanned by positioning a "reference line" on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. METHODS: To evaluate the operator in vivo measurement precision, we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner's software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled six new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. RESULTS: In vivo precision errors were up to threefold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. The inter-operator precision errors were significantly greater than the short-term intra-operator precision (p < 0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators and lower inter-operator reproducibility (p < 0.001). Precision errors were significantly greater for the radius than for the tibia. CONCLUSION: Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online ( http://webapps.radiology.ucsf.edu/refline/ ).

Successful treatment of traumatic spinal epidural haematoma with fluoroscopically-guided percutaneous drainage: a report of two cases.

We report two cases of spinal epidural haematoma that were successfully treated with percutaneous drainage. The patients initially presented with severe backache and progressive neurological symptoms due to traumatic epidural haematoma. After fluoroscopically-guided percutaneous drainage and irrigation, rapid physical decompression and full recovery was observed in both patients. To the best of our knowledge, this is the first report indicating that traumatic spinal epidural haematoma can be successfully treated with fluoroscopically-guided percutaneous drainage. Because percutaneous puncture under fluoroscopy is less invasive than surgery, we recommend considering this procedure as a non-operative treatment option for epidural haematoma.

In vivo assessment of bone structure and estimated bone strength by first- and second-generation HR-pQCT.

UNLABELLED: Bone strength is dependent on bone density and microstructure. High-resolution peripheral quantitative computed tomography (HR-pQCT) can measure microstructure but is somewhat limited due to its resolution. We compared a new HR-pQCT scanner to existing technology and found very good agreement for most parameters. This study will be important when interpreting results from different devices. INTRODUCTION: Recently, a second-generation HR-pQCT scanner (XCT2) has been developed with a higher nominal isotropic resolution (61 µm) compared to the first-generation device (XCT1, 82 µm). It is unclear how in vivo measurements from these two devices compare. In this study, we obtained and analyzed in vivo XCT1 and XCT2 measurements of bone microarchitecture and estimated strength. METHODS: We scanned 51 adults (16 men and 35 women, age 44.8 ± 16.0) on both XCT2 and XCT1 on the same day. We first compared XCT1 and XCT2 measurements obtained using their respective standard patient protocols. In XCT1, microarchitecture parameters were derived, while XCT2 measurements were directly measured. We also compared XCT2-D with XCT1 by finding the overlapping regions of interest and using the standard patient protocol for XCT1. RESULTS: We obtained excellent agreement between XCT1 and XCT2 for most of the volumetric bone mineral density (vBMD), trabecular and cortical measurements (All R (2) > 0.820) except for cortical porosity at the radius (R (2) = 0.638), trabecular number (R (2) = 0.694, 0.787) and trabecular thickness (R (2) = 0.569, 0.527) at both radius and tibia, respectively. XCT1 and XCT2-D measurements also had excellent agreement for most of the measurements (all R (2) > 0.870) except trabecular number (R (2) = 0.524, 0.706), trabecular thickness (R (2) = 0.758, 0.734) at both radius and tibia, respectively, and trabecular separation (R (2) = 0.656) at the radius. CONCLUSION: While some caution should be exercised for parameters that are more dependent on image resolution, results from our study indicate that second-generation scans can be compared to more widely available first-generation data and may be beneficial for multicenter and longitudinal studies using both scanner generations.

Na(+) /Ca(2+) exchanger-heterozygote knockout mice display increased relaxation in gastric fundus and accelerated gastric transit in vivo.

BACKGROUND: For the contraction and relaxation of gastric smooth muscles to occur, the intracellular Ca(2+) concentration must be increased and decreased, respectively. The Na(+) /Ca(2+) exchanger (NCX) is a plasma membrane transporter that is involved in regulating intracellular Ca(2+) concentrations. METHODS: To determine the role of NCX in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced relaxations in the circular muscles of the gastric fundus in NCX1 and NCX2 heterozygote knockout mice (HET). KEY RESULTS: The myenteric plexus layers and the longitudinal and circular muscle layers in the gastric fundus of wild-type mice (WT) were strongly immunoreactive to NCX1 and NCX2. EFS induced a transient relaxation that was apparent during the stimulus and a sustained relaxation that persisted after the end of the stimulus. The amplitudes of EFS-induced transient relaxation and sustained relaxation were greater in NCX1 HET and NCX2 HET than in WT. When an inhibitor of nitric oxide synthase was added following the EFS, neither NCX1 HET nor NCX2 HET exhibited transient relaxation, similar to WT. Furthermore, when a PACAP antagonist was added following the EFS, sustained relaxation in NCX1 HET and NCX2 HET was not observed, similar to WT. Next, we examined the effect of NCX heterozygous deficiency on relaxation in response to NO and PACAP in smooth muscles. The magnitude of NOR-1- and PACAP-induced relaxations in NCX1 HET and NCX2 HET was similar to that of WT. CONCLUSIONS & INFERENCES: In this study, we demonstrate that NCX1 and NCX2 expressed in neurons regulate the motility in the gastric fundus.

Shelter crowding and increased incidence of acute respiratory infection in evacuees following the Great Eastern Japan Earthquake and tsunami.

Although outbreaks of acute respiratory infection (ARI) at shelters are hypothesized to be associated with shelter crowding, no studies have examined this relationship. We conducted a retrospective study by reviewing medical records of evacuees presenting to one of the 37 clinics at the shelters in Ishinomaki city, Japan, during the 3-week period after the Great Eastern Japan Earthquake and tsunami in 2011. On the basis of a locally weighted scatter-plot smoothing technique, we categorized 37 shelters into crowded (mean space <5·5 m2/per person) and non-crowded (⩾5·5 m2) shelters. Outcomes of interest were the cumulative and daily incidence rate of ARI/10 000 evacuees at each shelter. We found that the crowded shelters had a higher median cumulative incidence rate of ARI [5·4/10 000 person-days, interquartile range (IQR) 0-24·6, P = 0·04] compared to the non-crowded shelters (3·5/10 000 person-days, IQR 0-8·7) using Mann-Whitney U test. Similarly, the crowded shelters had an increased daily incidence rate of ARI of 19·1/10 000 person-days (95% confidence interval 5·9-32·4, P < 0·01) compared to the non-crowded shelters using quasi-least squares method. In sum, shelter crowding was associated with an increased incidence rate of ARI after the natural disaster.

Proximal femur elastic behaviour is the same in impact and constant displacement rate fall simulation.

Understanding proximal femur fracture may yield new targets for fracture prevention screening and treatment. The goal of this study was to characterize force-displacement and failure behaviours in the proximal femur between displacement control and impact loading fall simulations. Twenty-one human proximal femurs were tested in two ways, first to a sub-failure load at a constant displacement rate, then to fracture in an impact fall simulator. Comparisons of sub-failure energy and stiffness were made between the tests at the same compressive force. Additionally, the impact failure tests were compared with previous, constant displacement rate failure tests (at 2 and 100mm/s) in terms of energy, yield force, and stiffness. Loading and displacement rates were characterized and related to specimen stiffness in the impact tests. No differences were observed between the sub-failure constant displacement and impact tests in the aforementioned metrics. Comparisons between failure tests showed that the impact group had the lowest absorbed energy, 24% lower maximum force and 160% higher stiffness than the 100mm/s group (p<0.01 for all), but suffered from low statistical power to differentiate the donor age and specimen BMD. Loading and displacement rates for the specimens tested using impact varied during each test and between specimens and did not show appreciable viscoelasticity. These results indicate that constant displacement rate testing may help understand sub-failure mechanical behaviour, but may not elucidate failure behaviours. The differences between the impact and constant displacement rate fall simulations have important ramifications for interpreting the results of previous experiments.

Classification of women with and without hip fracture based on quantitative computed tomography and finite element analysis.

UNLABELLED: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk. INTRODUCTION: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture. METHODS: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from -30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture. RESULTS: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9 %) and when analyzed separately by femoral neck fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4 %) CONCLUSIONS: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture.

Women with previous fragility fractures can be classified based on bone microarchitecture and finite element analysis measured with HR-pQCT.

UNLABELLED: High-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of distal radius and tibia bone microarchitecture and finite element (FE) estimates of bone strength performed well at classifying postmenopausal women with and without previous fracture. The HR-pQCT measurements outperformed dual energy x-ray absorptiometry (DXA) at classifying forearm fractures and fractures at other skeletal sites. INTRODUCTION: Areal bone mineral density (aBMD) is the primary measurement used to assess osteoporosis and fracture risk; however, it does not take into account bone microarchitecture, which also contributes to bone strength. Thus, our objective was to determine if bone microarchitecture measured with HR-pQCT and FE estimates of bone strength could classify women with and without low-trauma fractures. METHODS: We used HR-pQCT to assess bone microarchitecture at the distal radius and tibia in 44 postmenopausal women with a history of low-trauma fracture and 88 age-matched controls from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) study. We estimated bone strength using FE analysis and simulated distal radius aBMD from the HR-pQCT scans. Femoral neck (FN) and lumbar spine (LS) aBMD were measured with DXA. We used support vector machines (SVM) and a tenfold cross-validation to classify the fracture cases and controls and to determine accuracy. RESULTS: The combination of HR-pQCT measures of microarchitecture and FE estimates of bone strength had the highest area under the receiver operating characteristic (ROC) curve of 0.82 when classifying forearm fractures compared to an area under the curve (AUC) of 0.71 from DXA-derived aBMD of the forearm and 0.63 from FN and spine DXA. For all fracture types, FE estimates of bone strength at the forearm alone resulted in an AUC of 0.69. CONCLUSION: Models based on HR-pQCT measurements of bone microarchitecture and estimates of bone strength performed better than DXA-derived aBMD at classifying women with and without prior fracture. In future, these models may improve prediction of individuals at risk of low-trauma fracture.

Na(+) /Ca(2+) exchanger 2-heterozygote knockout mice display decreased acetylcholine release and altered colonic motility in vivo.

BACKGROUND: The Na(+) /Ca(2+) exchanger (NCX) is a plasma membrane transporter involved in regulating intracellular Ca(2+) concentrations. NCX is critical for Ca(2+) regulation in cardiac muscle, vascular smooth muscle, and nerve fibers. However, little is known about the physiological role of NCX in the myenteric neurons and smooth muscles of the gastrointestinal tract. METHODS: To determine the role of NCX1 and NCX2 in gastrointestinal tissues, we examined electric field stimulation (EFS)-induced responses in the longitudinal smooth muscle of the distal colon in NCX1- and NCX2-heterozygote knockout mice. KEY RESULTS: We found that the amplitudes of EFS-induced relaxation that persisted during EFS were greater in NCX2 heterozygous mice (HET) than in wild-type mice (WT). Under the nonadrenergic, noncholinergic (NANC) condition, EFS-induced relaxation in NCX2 HET was similar in amplitude to that of WT. In addition, an NCX inhibitor, YM-244769 enhanced EFS-induced relaxation but did not affect EFS-induced relaxation under the NANC condition, as in NCX2 HET. Unlike NCX2 HET, NCX1 HET displayed no marked changes in colonic motility. These results indicate that cholinergic function in the colon is altered in NCX2 HET. The magnitude of acetylcholine (ACh)-induced contraction in NCX2 HET was similar to that in WT. In contrast, EFS-induced ACh release was reduced in NCX2 HET compared with that in WT. CONCLUSIONS & INFERENCES: In this study, we demonstrate that NCX2 regulates colonic motility by altering ACh release onto the myenteric neurons of the distal colon.