Citations

Background Specific white-matter tract alterations in migraine remain to be elucidated. Using diffusion tensor imaging (DTI), this study investigated whether the integrity of white-matter tracts that underlie regions of the “pain matrix” is altered in migraine and interrogated whether the number of years lived with migraine modifies fibertract structure. Methods Global probabilistic tractography was used to assess the anterior thalamic radiations, the corticospinal tracts and the inferior longitudinal fasciculi in 23 adults with migraine and 18 healthy controls. Results Migraine patients show greater mean diffusivity (MD) in the left and right anterior thalamic radiations, the left corticospinal tract, and the right inferior longitudinal fasciculus tract. Migraine patients also show greater radial diffusivity (RD) in the left anterior thalamic radiations, the left corticospinal tract as well as the left and right inferior longitudinal fasciculus tracts. No group fractional anisotropy (FA) differences were identified for any tracts. Migraineurs showed a positive correlation between years lived with migraine and MD in the right anterior thalamic radiations ( r = 0.517; p = 0.012) and the left corticospinal tract ( r = 0.468; p = 0.024). Conclusion Results indicate that white-matter integrity is altered in migraine and that longer migraine history is positively correlated with greater alterations in tract integrity.

AbstractLung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single‐center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15–15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58–4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.

Background/Objective Between attacks, migraine is associated with hypersensitivities to sensory stimuli. The objective of this study was to investigate hypersensitivity to pain in migraineurs between attacks. Methods Cutaneous heat pain thresholds were measured in 112 migraineurs, migraine free for ≥48 hours, and 75 healthy controls. Pain thresholds at the head and at the arm were compared between migraineurs and controls using two-tailed t-tests. Among migraineurs, correlations between heat pain thresholds and headache frequency, allodynia symptom severity, and time interval until next headache were calculated. Results Migraineurs had lower pain thresholds than controls at the head (43.9℃ ± 3.2℃ vs. 45.1℃ ± 3.0℃, p = 0.015) and arm (43.2℃ ± 3.4℃ vs. 44.8℃ ± 3.3℃, p < 0.001). There were not significant correlations between pain thresholds and headache frequency or allodynia symptom severity. For the 41 migraineurs for whom time to next headache was known, there were positive correlations between time to next headache and pain thresholds at the head ( r = 0.352, p = 0.024) and arm ( r = 0.312, p = 0.047). Conclusions This study provides evidence that migraineurs have low heat pain thresholds between migraine attacks. Mechanisms underlying these lower pain thresholds could also predispose migraineurs to their next migraine attack, a hypothesis supported by finding positive correlations between pain thresholds and time to next migraine attack.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Exercise training is an established adjuvant therapy in heart failure; however, the effects of high-intensity interval training (HIIT) in HFpEF are unknown. We compared the effects of HIIT vs. moderate-intensity aerobic continuous training (MI-ACT) on peak oxygen uptake (V̇o2peak), left ventricular diastolic dysfunction, and endothelial function in patients with HFpEF. Nineteen patients with HFpEF (age 70 ± 8.3 yr) were randomized to either HIIT (4 × 4 min at 85-90% peak heart rate, with 3 min active recovery) or MI-ACT (30 min at 70% peak heart rate). Fifteen patients completed exercise training (HIIT: n = 9; MI-ACT: n = 6). Patients trained 3 days/wk for 4 wk. Before and after training patients underwent a treadmill test for V̇o2peak determination, 2D-echocardiography for assessment of left ventricular diastolic dysfunction, and brachial artery flow-mediated dilation (FMD) for assessment of endothelial function. HIIT improved V̇o2peak (pre = 19.2 ± 5.2 ml·kg−1·min−1; post = 21.0 ± 5.2 ml·kg−1·min−1; P = 0.04) and left ventricular diastolic dysfunction grade (pre = 2.1 ± 0.3; post = 1.3 ± 0.7; P = 0.02), but FMD was unchanged (pre = 6.9 ± 3.7%; post = 7.0 ± 4.2%). No changes were observed following MI-ACT. A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT (−3.3 ± 6.6 vs. +5.8 ± 10.7 ml/m2; P = 0.06). In HFpEF patients 4 wk of HIIT significantly improved V̇o2peak and left ventricular diastolic dysfunction. HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF.

Background Prior studies demonstrate reduced cortical thickness and volume in migraineurs. However, the effect of age on cortical thickness has not been assessed in migraineurs. In this study we investigated whether the process of aging on cortical thickness affects migraineurs differently compared to age-matched healthy controls, i.e. whether aging exacerbates cortical thinning in migraineurs. Methods Cortical thickness was estimated using a general linear model vertex-by-vertex approach for 32 healthy controls (mean age = 35.3 years; SD = 11.6) and 27 episodic migraine patients (mean age = 33.6 years; SD = 12.3). Results were modeled using a main effect analysis to estimate the effect of age on cortical thickness for each group separately, and an age-by-group analysis to estimate differences in age-related cortical thinning between migraine patients and normal controls. Results Although migraineurs and normal controls both have expected age-related thinning in many regions along the cortical mantle, migraineurs have age-related thinning of regions that do not thin in healthy controls, including: bilateral postcentral, right fusiform, and right temporal pole areas. Cortical thinning of these regions is more prominent with advancing age. Conclusion Results suggest that migraine is associated with atypical cortical aging, suggesting that the migraine disease process interacts with aging to affect cortical integrity.

Abstract Classic hyperacute rejection is dependent on the activation of the terminal components of complement. Recently, xenoantibodies with limited abilities to activate the classical pathway of complement in vitro have been implicated in the acute vascular rejection of xenografts. It is unclear how these Abs affect their pathogenic activities in vivo. In this study, we demonstrate the ability of an anti-Gal-α1,3Gal (Gal) IgG1, with modest complement-activating abilities in vitro, to induce xenograft rejection. This rejection was dependent on the activation of complement, on FcγR-mediated interactions, and on the presence of NK cells. Inhibition of any one of these factors resulted in the abrogation of IgG1-mediated rejection. In contrast, an anti-Gal IgG3 mAb induced classic, hyperacute rejection that was solely dependent on complement activation. Our observations implicate two types of IgG-mediated rejection; one that is dependent on complement activation, and a second that is uniquely dependent on complement, FcγR, and NK cells.

Abstract Cbl-b negatively regulates CD28-dependent T cell activation. In this report, we tested the hypothesis that CD28 and CTLA-4 have opposite roles in tuning T cell activation threshold by controlling the levels of Cbl-b protein expression. We demonstrate that CD28 costimulation potentiates TCR-induced Cbl-b degradation, whereas CTLA-4-B7 interaction is required for Cbl-b re-expression. In support of this finding, Cbl-b expression in CTLA-4 knockout (KO) T cells is significantly reduced, and treating CTLA-4KO mice with human CTLA-4Ig to block CD28-B7 interaction restores Cbl-b expression on T cells. Furthermore, CD28 and CTLA-4 costimulatory effects are compromised in Cbl-bKO T cells. These observations indicate that CD28 and CTLA-4 tightly regulate Cbl-b expression which is critical for establishing the threshold for T cell activation.

Objective The objective of this study was to identify brain regions having aberrant pain-induced activation in migraineurs, thereby gaining insight into particular aspects of pain processing that are atypical in migraineurs. Methods Functional magnetic resonance imaging assessed whole brain responses to painful heat in 24 adult episodic migraineurs who were at least 48 hours pain free and 27 healthy controls. Regions differentially activated in migraineurs compared to controls were identified. Activation intensities in these regions were correlated with headache frequency, number of migraine years, and time to next migraine attack. Results Migraineurs had greater pain-induced activation of lentiform nucleus, fusiform gyrus, subthalamic nucleus, hippocampus, middle cingulate cortex, premotor cortex, somatosensory cortex, and dorsolateral prefrontal cortex, and less activation in precentral gyrus and superior temporal gyrus. There were significant correlations between activation strength and headache frequency for middle cingulate ( r = 0.627, p = 0.001), right dorsolateral prefrontal cortex ( r = 0.568, p = 0.004), left fusiform gyrus ( r = 0.487, p = 0.016), left precentral gyrus ( r = 0.415, p = 0.044), and left hippocampus ( r = 0.404, p = 0.050) and with number of migraine years for left fusiform gyrus ( r = 0.425, p = 0.038). There were no significant correlations between activation strength and time to next migraine attack. Conclusions The majority of regions with enhanced pain-induced activation in headache-free migraineurs participate in cognitive aspects of pain perception such as attending to pain and pain memory. Enhanced cognitive pain processing by migraineurs might reflect cerebral hypersensitivity related to high expectations and hypervigilance for pain.

Endovascular coiling is the most common treatment for cerebral aneurysms. The treatment consists of deploying coils of different shapes and sizes into the aneurysm with the intent of reducing blood flow therein. While the treatment has been shown to be more effective than conventional surgical methods, it is successful in only 50–80% of cases, depending on the type of aneurysm [1]. Treatment success has been correlated with favorable post-treatment hemodynamics [2]. Understanding of the effects of coils on post-treatment hemodynamics is limited, however, due to limited in-vivo and in-vitro flow measurement techniques. Previous computational studies have also suffered from drastic assumptions about coil geometry.