Objectives:The wall-to-lumen ratio (WLR) of retinal arteries is a recognized surrogate of end-organ damage due to aging and/or arterial hypertension. However, parietal morphometry remains difficult to assess in vivo. Recently, it was shown that adaptive optics retinal imaging can resolve parietal structures of retinal arterioles in humans in vivo. Here, using adaptive optics retinal imaging, we investigated the variations of parietal thickness of small retinal arteries with blood pressure and focal vascular damage.Methods:Adaptive optics imaging of the superotemporal retinal artery was done in 49 treatment-naive individuals [mean age (±SD) 44.9 years (±14); mean systolic pressure 132 mmHg (±22)]. Semi-automated segmentation allowed extracting parietal thickness and lumen diameter. In a distinct cohort, adaptive optics images of arteriovenous nicking (AVN; n = 12) and focal arteriolar narrowing (FAN; n = 10) were also analyzed qualitatively and quantitatively.Results:In the cohort of treatment-naive individuals, by multiple regression taking into account age, body mass index, mean, systolic, diastolic and pulse blood pressure, the WLR was found positively correlated to mean blood pressure and age which in combination accounted for 43% of the variability of WLR. In the cohort of patients with focal vascular damage, neither FANs or AVNs showed evidence of parietal growth; instead, at sites of FANs, decreased outer diameter suggestive of vasoconstriction was consistently found, while at sites of AVNs venous narrowing could be seen in the absence of arteriovenous contact.Conclusion:High resolution imaging of retinal vessels by adaptive optics allows quantitative microvascular phenotyping, which may contribute to a better understanding and management of hypertensive retinopathy.
Intestinal expression of the high affinity Na ؉ /glucose cotransporter 1 (SGLT1), which absorbs dietary glucose and galactose, exhibits both circadian periodicity in its activity and induction by dietary carbohydrate. Because the daily variation in SGLT1 activity is established by the feeding schedule (whether ad libitum or imposed) and persists in the absence of food, this variation has been described as anticipatory. To delineate the mechanisms regulating SGLT1, its expression was examined in rats maintained in a 12-h photoperiod with free access to chow. SGLT1 mRNA levels varied significantly, with the maximum abundance occurring near the onset of dark and the minimum near the onset of light. The SGLT1 transcription rate was 7-fold higher in the morning (1000 -1100 h) than in the afternoon (1600 -1700 h). An element for hepatocyte nuclear factor 1 (HNF-1) was identified in the SGLT1 promoter that formed different complexes with small intestinal nuclear extracts, depending on the time when the source animal was killed. Serological tests indicated that HNF-1␣ was present in complexes throughout the day, while HNF-1 binding exhibited circadian periodicity. We propose that exchange of HNF-1 dimerization partners contributes to circadian changes in SGLT1 transcription. Because SGLT1 mRNA levels also varied in rhesus monkeys (offset by approximately one-half day from rats), a similar mechanism appears to be present in primates.
Repetitive thinking styles such as rumination are considered to be a key factor in the development and maintenance of mental disorders. Different situational triggers (e.g., social stressors) have been shown to elicit rumination in subjects exhibiting such habitual thinking styles. At the same time, the process of rumination influences the adaption to stressful situations. The study at hand aims to investigate the effect of trait rumination on neuronal activation patterns during the Trier Social Stress Test (TSST) as well as the physiological and affective adaptation to this high-stress situation.MethodsA sample of 23 high and 22 low ruminators underwent the TSST and two control conditions while their cortical hemodynamic reactions were measured with functional near-infrared spectroscopy (fNIRS). Additional behavioral, physiological and endocrinological measures of the stress response were assessed.ResultsSubjects showed a linear increase from non-stressful control conditions to the TSST in cortical activity of the cognitive control network (CCN) and dorsal attention network (DAN), comprising the bilateral dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG) and superior parietal cortex/somatosensory association cortex (SAC). During stress, high ruminators showed attenuated cortical activity in the right IFG, whereby deficits in IFG activation mediated group differences in post-stress state rumination and negative affect.ConclusionsAberrant activation of the CCN and DAN during social stress likely reflects deficits in inhibition and attention with corresponding negative emotional and cognitive consequences. The results shed light on possible neuronal underpinnings by which high trait rumination may act as a risk factor for the development of clinical syndromes.
Depression has been shown to be related to a variety of aberrant brain functions and structures. Particularly the investigation of alterations in functional connectivity (FC) in major depressive disorder (MDD) has been a promising endeavor, since a better understanding of pathological brain networks may foster our understanding of the disease. However, the underling mechanisms of aberrant FC in MDD are largely unclear. Using functional near-infrared spectroscopy (fNIRS) we investigated FC in the cortical parts of the default mode network (DMN) during resting-state in patients with current MDD. Additionally, we used qualitative and quantitative measures of psychological processes (e.g., state/trait rumination, mind-wandering) to investigate their contribution to differences in FC between depressed and non-depressed subjects. Our results indicate that 40% of the patients report spontaneous rumination during resting-state. Depressed subjects showed reduced FC in parts of the DMN compared to healthy controls. This finding was linked to the process of state/trait rumination. While rumination was negatively correlated with FC in the cortical parts of the DMN, mind-wandering showed positive associations.
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