Five single-point aquaporin-2 (AQP2) mutations that cause non-X-linked nephrogenic diabetes insipidus (NDI) were characterized to establish the cellular defect and to develop therapeutic strategies. In Xenopus oocytes expressing AQP2 cRNAs, single-channel water permeabilities of mutants L22V, T126M, and A147T were similar to that of wild-type AQP2, whereas R187C and C181W were nonfunctional. In

This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.

Background Pericardial fat volume (PFV) and thoracic fat volume (TFV) can be routinely measured from noncontrast CT (NCT) performed for calculating coronary calcium score (CCS) and may predict major adverse cardiovascular event (MACE) risk. Methods From a registry of 2751 asymptomatic patients without known CAD and 4-year follow-up for MACE (cardiac death, myocardial infarction, stroke, late revascularization) after NCT, we compared 58 patients with MACE (“EVENTS”) to 174 same-sex event-free controls matched by a propensity score to account for age, risk factors, and CCS. TFV was automatically calculated, and PFV was calculated with manual assistance in defining the pericardial contour, within which fat voxels were automatically identified. Independent relationships of PFV and TFV to MACE were evaluated using conditional multivariable logistic regression. Results EVENTS had higher mean PFV (101.8±49.2 cm3 vs. 84.9±37.7 cm3, p=0.007) and TFV (204.7±90.3 cm3 vs. 177±80.3 cm3, p=0.029) and higher frequencies of PFV>125 cm3 (33% vs. 14%, p=0.002) and TFV>250 cm3 (31% vs. 17%, p=0.025). After adjusting for Framingham Risk Score, CCS, and body-mass-index, PFV and TFV were significantly associated with MACE (odds ratio (OR) 1.74, 95%CI 1.03–2.95 for each doubling of PFV; OR 1.78, 95%CI 1.01–3.14 for TFV). Areas-under-the-curve from receiver operating characteristic analyses showed a trend of improved MACE prediction when PFV was added to FRS and CCS (0.73 vs 0.68, p=0.058). Addition of PFV, but not TFV, to FRS and CCS improved estimated specificity (0.72 vs 0.66, p=0.008) and overall accuracy (0.70 vs 0.65, p=0.009) in predicting MACE. Conclusion Asymptomatic patients who experience MACE exhibit greater PFV on pre-MACE NCT when compared to event-free controls with similar cardiovascular risk profiles. Our preliminary findings suggest that PFV may help improve prediction of MACE.

Deep learning has the potential to improve automatic interpretation of MPI as compared with current clinical methods.

IMPORTANCE Pericoronary adipose tissue (PCAT) computed tomography (CT) attenuation measured from coronary CT angiography (CTA) may be a promising metric in identifying high-risk plaques. OBJECTIVE To determine whether high-risk plaque characteristics from coronary CTA are associated with PCAT CT attenuation in patients with a first acute coronary syndrome (ACS) and matched controls with stable coronary artery disease (CAD). DESIGN, SETTING, AND PARTICIPANTSThis retrospective, single-center case-control study (data were acquired at the University of Erlangen from 2009-2010) analyzed the CTA data sets of 19 patients who presented with ACS and 16 controls with stable CAD who were matched based on sex, age, and risk factors. Study observers were blinded to patients' clinical data. Semiautomated software was used to quantify and characterize plaques. The CT attenuation (Hounsfield unit [HU]) of PCAT was automatically measured around all lesions. MAIN OUTCOMES AND MEASURES To investigate the association between high-risk plaque characteristics from CTA and PCAT CT attenuation as a novel surrogate measure of coronary inflammation. RESULTS A total of 35 patients (mean [SD] age, 59.5 [11.3] years; 30 men [86%] and 5 women [14%]) were included in the analysis. Low-and intermediate-attenuation noncalcified plaque (NCP) burden were increased in culprit lesions (n = 19) compared with both nonculprit lesions (n = 55) in patients with ACS (12.6% vs 3.6%; P < .001; 38.4% vs 19.4%; P < .001) and the control group's highest-grade stenosis lesions (n = 16) (12.6% vs 5.6%; P = .002; 38.4% vs 22.1%; P < .001). Pericoronary adipose tissue attenuation was increased around culprit lesions (n = 19) compared with nonculprit lesions (n = 55) in patients with ACS (−69.1 HU vs −74.8 HU; P = .01) and highest-grade stenosis lesions in control patients (n = 16) (−69.1 HU vs −76.4 HU; P = .01). Pericoronary adipose tissue CT attenuation of all lesions in patients with ACS (n = 74) correlated more strongly with intermediate-attenuation (r = 0.393; P = .001) over low-attenuation (r = 0.221; P = .06) and high-attenuation NCP burden (r = −0.103; P = .38). In a multivariable analysis, low-and intermediate-attenuation NCP burden and PCAT CT attenuation were independently associated with the presence of culprit lesions (P < .05). CONCLUSIONS AND RELEVANCE Pericoronary CT attenuation was increased around culprit lesions compared with nonculprit lesions of patients with ACS and the lesions of matched controls. Combined quantitative high-risk plaque features and PCAT CT attenuation may allow for a more reliable identification of vulnerable plaques.

EAT volume was higher and density lower in subjects with coronary calcium compared to subjects with CCS = 0, with similar EAT volume in CCS<100 and CCS≥100. Lower EAT density and increased EAT volume were associated with coronary calcification, serum levels of plaque inflammatory markers and MACE, suggesting that dysfunctional EAT may be linked to early plaque formation and inflammation.

A recently developed camera system for high-speed SPECT (HS-SPECT) myocardial perfusion imaging shows excellent correlation with conventional SPECT. Our goal was to test the diagnostic accuracy of an automated quantification of combined upright and supine myocardial SPECT for detection of coronary artery disease (CAD) (≥70% luminal diameter stenosis or, in left main coronary artery, ≥50% luminal diameter stenosis) in comparison to invasive coronary angiography (ICA). Methods We studied 142 patients undergoing upright and supine HS-SPECT, including 56 consecutive patients (63% men; mean age 6 ± SD, 64 ± 13 y; 45% exercise stress) without known CAD who underwent diagnostic ICA within 6 mo of HS-SPECT and 86 consecutive patients with a low likelihood of CAD. Reference limits for upright and supine HS-SPECT were created from studies of patients with a low likelihood of CAD. Automated software adopted from supine–prone analysis was used to quantify the severity and extent of perfusion abnormality and was expressed as total perfusion deficit (TPD). TPD was obtained for upright (U-TPD), supine (S-TPD), and combined upright–supine acquisitions (C-TPD). Stress U-TPD ≥ 5%, S-TPD ≥ 5%, and C-TPD ≥ 3% myocardium were considered abnormal for per-patient analysis, and U-TPD, S-TPD, and C-TPD ≥ 2% in each coronary artery territory were considered abnormal for per-vessel analysis. Results On a per-patient basis, the sensitivity was 91%, 88%, and 94% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 59%, 73%, and 86% for U-TPD, S-TPD, and C-TPD, respectively. C-TPD had a larger area under the receiver-operating-characteristic curve than U-TPD or S-TPD for identification of stenosis ≥ 70% (0.94 vs. 0.88 and 0.89, P < 0.05 and not significant, respectively). On a per-vessel basis, the sensitivity was 67%, 66%, and 69% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 91%, 94%, and 97% for U-TPD, S-TPD, and C-TPD, respectively (P = 0.02 for specificity U-TPD vs. C-TPD). Conclusion In this first comparison of HS-SPECT with ICA, new automated quantification of combined upright and supine HS-SPECT shows high diagnostic accuracy for detecting clinically significant CAD, with findings comparable to those reported using conventional SPECT.

Aims Increased attenuation of pericoronary adipose tissue (PCAT) around the proximal right coronary artery (RCA) from coronary computed tomography angiography (CTA) has been shown to be associated with coronary inflammation and improved prediction of cardiac death over plaque features. Our aim was to investigate whether PCAT CT attenuation is related to progression of coronary plaque burden. Methods and results We analysed CTA studies of 111 stable patients (age 59.2 ± 9.8 years, 77% male) who underwent sequential CTA (3.4 ± 1.6 years between scans) with identical acquisition protocols. Total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density non-calcified plaque (LD-NCP) volumes and corresponding burden (plaque volume × 100%/vessel volume) were quantified using semi-automated software. PCAT CT attenuation (HU) was measured around the proximal RCA, the most standardized method for PCAT analysis. Patients with an increase in NCP burden (n = 51) showed an increase in PCAT attenuation, whereas patients with a decrease in NCP burden (n = 60) showed a decrease {4.4 [95% confidence interval (CI) 2.6–6.2] vs. −2.78 (95% CI −4.6 to −1.0) HU, P < 0.0001}. Changes in PCAT attenuation correlated with changes in the burden of NCP (r = 0.55, P < 0.001) and LD-NCP (r = 0.24, P = 0.01); but not CP burden (P = 0.3). Increased baseline PCAT attenuation ≥−75 HU was independently associated with increase in NCP (odds ratio 3.07, 95% CI 1.4–7.0; P < 0.008) and TP burden on follow-up CTA. Conclusion PCAT attenuation measured from routine CTA is related to the progression of NCP and TP burden. This imaging biomarker may help to identify patients at increased risk of high-risk plaque progression and allow monitoring of beneficial changes from medical therapy.