Purpose: Myocardial strain is increasingly used to assess left ventricular (LV) function. Incorporation of LV deformation into finite element (FE) modeling environment with subsequent strain calculation will allow analysis to reach its full potential. We describe a new kinematic model-based analysis framework (KMAF) to calculate strain from 3D cine-DENSE (displacement encoding with stimulated echoes) MRI. Methods: Cine-DENSE allows measurement of 3D myocardial displacement with high spatial accuracy. The KMAF framework uses cine cardiovascular magnetic resonance (CMR) to facilitate cine-DENSE segmentation, interpolates cine-DENSE displacement, and kinematically deforms an FE model to calculate strain. This framework was validated in an axially compressed gel phantom and applied in 10 healthy sheep and 5 sheep after myocardial infarction (MI). Results: Excellent Bland-Altman agreement of peak circumferential (E-cc) and longitudinal (E-ll) strain (mean difference = 0.021 +/- 0.04 and -0.006 +/- 0.03, respectively), was found between KMAF estimates and idealized FE simulation. E-rr had a mean difference of -0.014 but larger variation (+/- 0.12). Cine-DENSE estimated end-systolic (ES) E-cc, E-ll and E-rr exhibited significant spatial variation for healthy sheep. Displacement magnitude was reduced on average by 27%, 42%, and 56% after MI in the remote, adjacent and MI regions, respectively. Conclusions: The KMAF framework allows accurate calculation of 3D LV Ecc and Ell from cine-DENSE.

Objective Eye health among the homeless community is important, as poor vision makes this population vulnerable and adds significantly to the social and health burden. There is limited knowledge on patient follow-up rates for their eye conditions and barriers to accessing care in this population. The purpose of this retrospective chart review study is to examine follow-up rates and barriers to care for patients referred from a free, medical-student run ophthalmology clinic at a homeless shelter. Methods All patients evaluated at a free ophthalmology clinic from September 2017 to September 2018 were included; no patients were excluded. If indicated, patients were referred for advanced ophthalmologic care at a local county hospital and free eyeglasses at a nonprofit organization. Primary outcomes were follow-up rates at the county hospital and nonprofit organization. Secondary outcomes included prespecified baseline variables hypothesized to be associated with follow-up rates. These categorical variables were compared with Chi-square testing to determine their association with follow-up rates. The hypothesis being tested was formulated before data collection. Results Of the 68 patients, 84% were males with a mean age of 50 years. Overall, 40 patients were referred for free eyeglasses and 17 to the county hospital. Of those referred, 14 patients presented for free eyeglasses and 7 presented to the county hospital. About 79% of patients with a pre-established primary care provider presented to their appointment compared with 20% of those without one (p = 0.03). The 44% of patients with a high school diploma presented while all patients without a high school diploma failed to present (p = 0.04). Vision-threatening conditions identified at the shelter clinic did not affect follow-up rates (p = 0.79). Conclusion Less than half of referred patients in our study presented to their appointments. Barriers to presentation included no primary care provider and lower educational status, with no improvement in follow-up rates among those referred for vision-threatening conditions. Interventions such as health coaching with particular attention to educating patients on the effects of vision-threatening conditions may be warranted, particularly for those not looped into the health care system and those of lower educational attainment.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.

Delayed graft function (DGF) is a frequent complication of renal transplantation, particularly in the setting of transplantation of kidneys derived from deceased donors and expanded-criteria donors. DGF results from tubular epithelial cell injury and has immediate and long term consequences. These include requirement for post-transplantation dialysis, increased incidence of acute rejection, and poorer long-term outcomes. DGF represents one of the clearest clinical examples of renal acute ischemia/reperfusion injury. Experimental studies have demonstrated that ischemia/reperfusion injury induces the synthesis of the full length secreted isoform of matrix metalloproteinase-2 (FL-MMP-2), as well as an intracellular N-terminal truncated MMP-2 isoform (NTT-MMP-2) that initiates an innate immune response. We hypothesized that the two MMP-2 isoforms mediate tubular epithelial cell injury in DGF. Archival renal biopsy sections from 10 protocol biopsy controls and 41 cases with a clinical diagnosis of DGF were analyzed for the extent of tubular injury, expression of the FL-MMP-2 and NTT-MMP-2 isoforms by immunohistochemistry (IHC), in situ hybridization, and qPCR to determine isoform abundance. Differences in transcript abundance were related to tubular injury score. Markers of MMP-2-mediated injury included TUNEL staining and assessment of peritubular capillary density. There was a clear relationship between tubular epithelial cell expression of both FL-MMP-2 and NTT-MMP-2 IHC with the extent of tubular injury. The MMP-2 isoforms were detected in the same tubular segments and were present at sites of tubular injury. qPCR demonstrated highly significant increases in both the FL-MMP-2 and NTT-MMP-2 transcripts. Statistical analysis revealed highly significant associations between FL-MMP-2 and NTT-MMP-2 transcript abundance and the extent of tubular injury, with NTT-MMP-2 having the strongest association. We conclude that two distinct MMP-2 isoforms are associated with tubular injury in DGF and offer novel therapeutic targets for the prevention of this disorder.