OBJECTIVE

Human immunodeficiency virus (HIV)-related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs).

METHODS

The authors compared gene expression profiles of CD14(+) cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. RELEVANCE FOR NURSING PRACTICE: Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14(+) cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients.

CONCLUSIONS

The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction.

To determine the immediate effects of bilevel non-invasive ventilation plus oxygen (NIV+O(2)) during exercise compared to exercise with O(2) alone in people recovering from acute on chronic hypercapnic respiratory failure (HRF), a randomised crossover study with repeated measures was performed. Eighteen participants performed six minute walk tests (6MWT) and 16 participants performed unsupported arm exercise (UAE) tests with NIV+O(2) and with O(2) alone in random order. Distance walked increased by a mean of 43.4m (95% CI 14.1 to 72.8, p=0.006) with NIV+O(2) compared to exercise with O(2) alone. In addition, isotime oxygen saturation increased by a mean of 5% (95% CI 2-7, p=0.001) and isotime dyspnoea was reduced [median 2 (interquartile range (IQR) 1-4) versus 4 (3-5), p=0.028] with NIV+O(2). A statistically significant increase was also observed in UAE endurance time with NIV+O(2) [median 201s (IQR 93-414) versus 157 (90-342), p=0.033], and isotime perceived exertion (arm muscle fatigue) was reduced by a mean of 1.0 on the Borg scale (95% CI -1.9 to -0.1, p=0.037) compared with O(2) alone. Non-invasive ventilation plus O(2) during walking resulted in an immediate improvement in distance walked and oxygen saturation, and a reduction in dyspnoea compared to exercise with O(2) alone in people recovering from acute on chronic HRF. The reduction of dyspnoea during walking and arm muscle fatigue during UAE observed with NIV+O(2) may allow patients to better tolerate exercise early in the recovery period.

Functional near-infrared spectroscopy (fNIRS) can be combined with electroencephalography (EEG) to continuously monitor the hemodynamic signal evoked by epileptic events such as seizures or interictal epileptiform discharges (IEDs, aka spikes). As estimation methods assuming a canonical shape of the hemodynamic response function (HRF) might not be optimal, we sought to model patient-specific HRF (sHRF) with a simple deconvolution approach for IED-related analysis with EEG-fNIRS data. Furthermore, a quadratic term was added to the model to account for the nonlinearity in the response when IEDs are frequent. Prior to analyzing clinical data, simulations were carried out to show that the HRF was estimable by the proposed deconvolution methods under proper conditions. EEG-fNIRS data of five patients with refractory focal epilepsy were selected due to the presence of frequent clear IEDs and their unambiguous focus localization. For each patient, both the linear sHRF and the nonlinear sHRF were estimated at each channel. Variability of the estimated sHRFs was seen across brain regions and different patients. Compared with the SPM8 canonical HRF (cHRF), including these sHRFs in the general linear model (GLM) analysis led to hemoglobin activations with higher statistical scores as well as larger spatial extents on all five patients. In particular, for patients with frequent IEDs, nonlinear sHRFs were seen to provide higher sensitivity in activation detection than linear sHRFs. These observations support using sHRFs in the analysis of IEDs with EEG-fNIRS data.

BACKGROUND

Reactive oxygen species (ROS) have been shown to enhance the proliferation of cancer cells. NADPH oxidases (NOX4) are a major intracellular source of ROS and are found to be associated with cancer and tumor cell invasion. Therefore, the purpose of this study is to evaluate the expression of NOX4 protein in human retinoblastoma.

METHODS

Immunohistochemical expression of NOX4 protein was analyzed in 109 specimens from prospective cases of retinoblastoma and then correlated with clinicopathological parameters and patient survival. Western blotting confirmed and validated the immunoreactivity of NOX4 protein.

RESULTS

In our study we found a male preponderance (55.9 %), and 25/109 (22.9 %) were bilateral. Massive choroidal invasion was the histopathological high-risk factor (HRF) most frequently observed, in 42.2 % of the cases. NOX4 protein was expressed in 67.88 % (74/109) of primary retinoblastoma cases and was confirmed by Western blotting. NOX4 was statistically significant with massive choroidal invasion and pathological TNM staging. There was a statistically significant difference in overall survival in patients with NOX4 expression (p = 0.0461).

CONCLUSIONS

This is the first study to show the expression of NOX4 protein in retinoblastoma tumors. Hence, a retinoblastoma tumor may exhibit greater ROS stress. This protein may prove to be useful as a future therapeutic target for improving the management of retinoblastoma.

For a reliable estimation of neuronal activation based on BOLD fMRI measurements an accurate model of the hemodynamic response is essential. Since a large part of basic neuroscience research is based on small animal data, it is necessary to characterize a hemodynamic response function (HRF) which is optimized for small animals. Therefore, we have determined and investigated the HRFs of rats obtained under a variety of experimental conditions in the primary somatosensory cortex. Measurements were performed on animals of different sex and strain, under different anesthetics, with and without ventilation and using different stimulation modalities. All modalities of stimulation used in this study induced neuronal activity in the primary somatosensory cortex or in subcortical regions. Since the HRFs of the BOLD responses in the primary somatosensory cortex showed a close concordance for the different conditions, we were able to determine a cortical rat HRF. This HRF is based on 143 BOLD measurements of 76 rats and can be used for statistical parametric mapping. It showed substantially faster progression than the human HRF, with a maximum after (2.8) s, and a following undershoot after (6.1) s. If the rat HRF was used statistical analysis of rat data showed a significantly improved detection performance in the somatosensory cortex in comparison to the commonly used HRF based on measurements in humans.

Ample evidence links dysregulation of the stress response to the risk for psychiatric disorders. However, we lack an integrated understanding of mechanisms that are adaptive during the acute stress response but potentially pathogenic when dysregulated. One mechanistic link emerging from rodent studies is the interaction between stress effectors and neurovascular coupling, a process that adjusts cerebral blood flow according to local metabolic demands. Here, using task-related fMRI, we show that acute psychosocial stress rapidly impacts the peak latency of the hemodynamic response function (HRF-PL) in temporal, insular, and prefrontal regions in two independent cohorts of healthy humans. These latency effects occurred in the absence of amplitude effects and were moderated by regulatory genetic variants of KCNJ2, a known mediator of the effect of stress on vascular responsivity. Further, hippocampal HRF-PL correlated with both cortisol response and genetic variants that influence the transcriptional response to stress hormones and are associated with risk for major depression. We conclude that acute stress modulates hemodynamic response properties as part of the physiological stress response and suggest that HRF indices could serve as endophenotype of stress-related disorders.

Background: Hypofractionated radiotherapy (HFR) is sometimes used in the treatment of glioblastoma multiforme (GBM). The efficacy and safety of HFR is still under investigation. The aim of this systematic review and meta-analysis was to provide a comprehensive summary of the efficacy and safety of HFR, and to compare the efficacy and safety of HFR and conventional fraction radiotherapy (CFR) for the treatment of patients with GBM, based on the results of randomized controlled trials (RCTs). Methods: A literature search was conducted to identify Phase II and III trials o comparing the efficacy and safety of HFR and CFR. Study selection, data extraction, and quality assessment, were conducted by two independent researchers. The analysis was performed using RevMan 5.3 and Stata 12.0. Results: Sixteen Phase II and III trials were included in the systematic review, and four RCTs were included in the meta-analysis. Participants treated with HRF and CRF had comparable overall survival (OS) (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.72-1.22, P = 0.64) and progression-free survival (PFS) (HR: 1.09, 95% CI: 0.60-1.95, P = 0.79), and similar rates of adverse events. However, in participants aged >70 years, those who received HFR had a higher OS than those who received CFR (HR: 0.59, 95% CI: 0.37-0.93, P = 0.02). Conclusions: HRF is efficacious and safe for the treatment of GBM. In individuals aged >70 years, treatment with HRF is superior to CFR in terms of OS. The role of HFR in the treatment of GBM in younger individuals and those with good prognostic factors requires further research.

The native particulate guanylyl cyclase B receptor (pGC-B) activator, C-type natriuretic peptide (CNP), induces anti-remodeling actions in the heart and kidney through the generation of the second messenger 3', 5' cyclic guanosine monophosphate (cGMP). Indeed fibrotic remodeling, particularly in cardiorenal disease states, contributes to disease progression and thus, has been a key target for drug discovery and development. Although the pGC-B/cGMP system has been perceived as a promising anti-fibrotic pathway, its therapeutic potential is limited due to the rapid degradation and catabolism of CNP by neprilysin (NEP) and natriuretic peptide clearance receptor (NPRC). The goal of this study was to bioengineer and test in vitro and in vivo a novel pGC-B activator, C53. Here we established that C53 selectively generates cGMP via the pGC-B receptor and is highly resistant to NEP and has less interaction with NPRC in vitro. Furthermore in vivo, C53 had enhanced cGMP-generating actions that paralleled elevated plasma CNP-like levels, thus indicating a longer circulating half-life compared to CNP. Importantly in human cardiac fibroblasts (HCFs) and renal fibroblasts (HRFs), C53 exerted robust cGMP-generating actions, inhibited TGFβ-1 stimulated HCFs and HRFs proliferation chronically and suppressed the differentiation of HCFs and HRFs to myofibroblasts. The current findings advance innovation in drug discovery and highlight C53 as a novel pGC-B activator with sustained in vivo activity and anti-fibrotic actions in vitro. Future studies are warranted to explore the efficacy and therapeutic opportunity of C53 targeting fibrosis in cardiorenal disease states and beyond.

The world-wide usage and partly abuse of veterinary antibiotics resulted in a pressing need to control residues in animal-derived foods. Large-scale screening for residues of antibiotics is typically performed by microbial agar diffusion tests. This work employing high-performance thin-layer chromatography (HPTLC) combined with bioautography and electrospray ionization mass spectrometry introduces a rapid and efficient method for a multi-class screening of antibiotic residues. The viability of the bioluminescent bacterium Aliivibrio fischeri to the studied antibiotics (16 species of 5 groups) was optimized on amino plates, enabling detection sensitivity down to the strictest maximum residue limits. The HPTLC method was developed not to separate the individual antibiotics, but for cleanup of sample extracts. The studied antibiotics either remained at the start zones (tetracyclines, aminoglycosides, fluoroquinolones, and macrolides) or migrated into the front (amphenicols), while interfering co-extracted matrix compounds were dispersed at hRf 20-80. Only after a few hours, the multi-sample plate image clearly revealed the presence or absence of antibiotic residues. Moreover, molecular information as to the suspected findings was rapidly achieved by HPTLC-mass spectrometry. Showing remarkable sensitivity and matrix-tolerance, the established method was successfully applied to milk and kidney samples.

Histamine-releasing activities on human basophils have been studied as potential allergy-causing agents for four decades. An IgE-dependent histamine-releasing factor (HRF) was recently shown to interact with a subset of immunoglobulins. Peptides or recombinant proteins that block the interactions between HRF and IgE have emerged as promising anti-allergic therapeutics, as administration of them prevented or ameliorated type 2 inflammation in animal models of allergic diseases such as asthma and food allergy. Basic and clinical studies support the notion that HRF amplifies IgE-mediated activation of mast cells and basophils. We discuss how secreted HRF promotes allergic inflammation in vitro and in vivo complex disease settings.

UNASSIGNED

Histamine releasing factor (HRF) is a unique cytokine known to regulate a variety of immune cells in late allergic reactions. In the previous study, we revealed that the biologically active form of HRF is the dimerized translationally controlled tumor protein (dTCTP) for the first time, and confirmed the secretion of IL-8 cytokine by dTCTP in human bronchial epithelial cells. However, the signaling pathway by which dTCTP promotes the secretion of IL-8 is not known.

UNASSIGNED

When the cells were stimulated with dTCTP, the canonical NF-κB pathway and ERK, JNK and p38 MAPK become activated. dTCTP promoted transcription of IL-8, which involved NF-κB and AP-1 transcription factors. NF-κB was found to be essential for the transcriptional activation of IL-8, while AP-1 was partially responsible for the transcriptional activation by dTCTP. p38 MAPK was found to be involved in post-transcriptional regulation of dTCTP by stabilizing IL-8 mRNA.

UNASSIGNED

This study demonstrated that dTCTP induces IL-8 secretion in BEAS-2B cells through transcriptional and post-transcriptional regulation of MAPK and NF-κB pathways. This study provides insight into the mechanism by which dTCTP induces inflammation.

OBJECTIVE

To estimate the cost-effectiveness of using an extensively hydrolyzed casein formula (eHCF) containing the probiotic Lactobacillus rhamnosus GG, (eHCF + LGG; Nutramigen LGG) as first-line management for cow's milk allergy (CMA) compared with eHCF alone, soy-based formulae (SBF), hydrolyzed rice formulae (HRF), and amino acid formulae (AAF) in Italy, from the perspective of the Italian National Health Service (INHS) and parents.

METHODS

Decision modeling was used to estimate the probability of infants developing tolerance to cow's milk by 18 months, based on an observational study dataset. The model also estimated the cost (at 2012/2013 prices) of health care resource use funded by the INHS and formulae paid for by parents over 18 months after starting a formula, as well as the relative cost-effectiveness of each of the formulae.

RESULTS

The probability of developing tolerance to cow's milk by 18 months was higher among infants with either IgE-mediated or non-IgE-mediated allergy who were fed eHCF + LGG compared to those fed one of the other formulae. The total health care cost of initially feeding infants with eHCF + LGG was less than that of feeding infants with one of the other formulae. Hence, eHCF + LGG affords the greatest value for money to both the INHS and parents of infants with either IgE-mediated or non-IgE-mediated CMA.

CONCLUSIONS

Using eHCF + LGG instead of eHCF, SBF, HRF, or an AAF for first-line management of newly diagnosed infants with CMA in Italy affords a cost-effective use of publicly funded resources, and is cost-effective from the parents' perspective, since it improves outcome for less cost. A randomized controlled study showing faster tolerance development in children receiving a probiotic-containing formula is required before this conclusion can be confirmed.

BACKGROUND

Children with visual impairments (VI) often reveal higher levels of sedentary time and lower levels of fundamental motor skills (FMS), health-related fitness (HRF) and physical activity (PA) than peers without visual impairments. Extrapolating correlates of HRF and PA are important to develop targeted intervention strategies aimed at improving health- and movement-based outcomes.

OBJECTIVE

The purpose of this study was to examine associations among FMS (divided into locomotor and object control skills), HRF, and home- and sport-camp based PA measures in children with VI.

METHODS

Children with VI (N = 66; 9-18 years) completed PA, HRF (including cardio-respiratory fitness, muscular strength and endurance), and FMS measures during a seven-day period. Partial and zero-order correlations, which included controlling for age, degree of VI, and BMI z-score were performed.

RESULTS

When controlling for vision, age, and BMI z-score, home-based self-report PA moderately correlated with camp-based accelerometer data (p < .001); home-based and camp-based PA associated with object control and locomotor subscales (p < .001); object control and locomotor skills were the most influential factors above and beyond vision associating with both PA measures. Cardiorespiratory fitness and grip strength were significantly associated with both object control and locomotor skills (p < .001).

CONCLUSIONS

Future intervention strategies that target increasing PA and HRF levels for children with VI should consider focusing upon both object control and locomotor skill development.

LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic effect of TCTP is related to its pro-inflammatory functions. An initial characterization of LiTCTP in animal models showed that this toxin can increase the microvascular permeability of skin vessels and induce paw edema in a dose-dependent manner. We evaluated the role of LiTCTP in vitro and in vivo in the inflammatory and allergic aspects that undergo the biological responses observed in Loxoscelism, the clinical condition after an accident with Loxosceles spiders. Our results showed LiTCTP recombinant toxin (LiRecTCTP) as an essential synergistic factor for the dermonecrotic toxin actions (LiRecDT1, known as the main toxin in the pathophysiology of Loxoscelism), revealing its contribution to the exacerbated inflammatory response clinically observed in envenomated patients.

Nucleosomes are the most abundant protein-DNA complexes in eukaryotes that provide compaction of genomic DNA and are implicated in regulation of transcription, DNA replication and repair. The details of DNA positioning on the nucleosome and the DNA conformation can provide key regulatory signals. Hydroxyl-radical footprinting (HRF) of protein-DNA complexes is a chemical technique that probes nucleosome organization in solution with a high precision unattainable by other methods. In this work we propose an integrative modeling method for constructing high-resolution atomistic models of nucleosomes based on HRF experiments. Our method precisely identifies DNA positioning on nucleosome by combining HRF data for both DNA strands with the pseudo-symmetry constraints. We performed high-resolution HRF for Saccharomyces cerevisiae centromeric nucleosome of unknown structure and characterized it using our integrative modeling approach. Our model provides the basis for further understanding the cooperative engagement and interplay between Cse4p protein and the A-tracts important for centromere function.

Diabetic retinopathy (DR) is a vascular disease of the neuroretina characterised by hyperglycaemia and inflammation. Current DR therapies target late-stage vascular defects and there is evidence to suggest that they contribute to geographic atrophy and retinal ganglion cell death long term. Therefore, alternative treatments that target common upstream disease mechanisms are needed. Recent studies have shown that connexin43 hemichannel blockers can reduce inflammation and prevent vessel leak in brain and spinal cord lesions. The aim of this study was to evaluate the effectiveness of a connexin43 hemichannel blocker (Peptide5) in a mouse model of DR in which pro-inflammatory cytokines, IL-1β and TNF-α, were intravitreally injected into non-obese diabetic (NOD, hyperglycaemic) mice. Fundus and optical coherence tomography images were taken to evaluate vessel dilation and beading as well as retinal and vitreous hyper-reflective foci (HRF). Immunohistochemistry was performed to assess levels of astrogliosis, microgliosis and inflammasome activation. Results showed that Peptide5 injection lowered the incidence of vessel dilation and beading, decreased the severity of vitreous and retinal HRF, and reduced sub-retinal fluid accumulation compared to the vehicle group. Furthermore, Peptide5 led to reduced connexin43 and GFAP upregulation, inhibited microglial infiltration into the outer nuclear layer and prevented upregulation of inflammasome markers compared to vehicle. The present study provides evidence in support of Peptide5, and connexin43 hemichannel block in general, as a potential upstream approach for the treatment of DR. KEY MESSAGES: Connexin43 is upregulated in a novel mouse model of diabetic retinopathy (DR). Connexin43 hemichannel block inhibits inflammation and inflammasome activation. Connexin43 hemichannel block prevents the development of clinical DR signs. Connexin43 hemichannel block is a potential upstream approach for DR treatment.

Epidemiological studies demonstrate that dimensions of retinal vessels change with ocular diseases, coronary heart disease and stroke. Different metrics have been described to quantify these changes in fundus images, with arteriolar and venular calibers among the most widely used. The analysis often includes a manual procedure during which a trained grader differentiates between arterioles and venules. This step can be time-consuming and can introduce variability, especially when large volumes of images need to be analyzed. In light of the recent successes of fully convolutional networks (FCNs) applied to biomedical image segmentation, we assess its potential in the context of retinal artery-vein (A/V) discrimination. To the best of our knowledge, a deep learning (DL) architecture for simultaneous vessel extraction and A/V discrimination has not been previously employed. With the aim of improving the automation of vessel analysis, a novel application of the U-Net semantic segmentation architecture (based on FCNs) on the discrimination of arteries and veins in fundus images is presented. By utilizing DL, results are obtained that exceed accuracies reported in the literature. Our model was trained and tested on the public DRIVE and HRF datasets. For DRIVE, measuring performance on vessels wider than two pixels, the FCN achieved accuracies of 94.42% and 94.11% on arteries and veins, respectively. This represents a decrease in error of 25% over the previous state of the art reported by Xu et al. (2017). Additionally, we introduce the HRF A/V ground truth, on which our model achieves 96.98% accuracy on all discovered centerline pixels. HRF A/V ground truth validated by an ophthalmologist, predicted A/V annotations and evaluation code are available at https://github.com/rubenhx/av-segmentation.

Retinal vessel segmentation (RVS) is a significant source of useful information for monitoring, identification, initial medication, and surgical development of ophthalmic disorders. Most common disorders, i.e., stroke, diabetic retinopathy (DR), and cardiac diseases, often change the normal structure of the retinal vascular network. A lot of research has been committed to building an automatic RVS system. But, it is still an open issue. In this article, a framework is recommended for RVS with fast execution and competing outcomes. An initial binary image is obtained by the application of the MISODATA on the preprocessed image. For vessel structure enhancement, B-COSFIRE filters are utilized along with thresholding to obtain another binary image. These two binary images are combined by logical AND-type operation. Then, it is fused with the enhanced image of B-COSFIRE filters followed by thresholding to obtain the vessel location map (VLM). The methodology is verified on four different datasets: DRIVE, STARE, HRF, and CHASE_DB1, which are publicly accessible for benchmarking and validation. The obtained results are compared with the existing competing methods.

While handcrafted radiomic features (HRFs) have shown promise in the field of personalized medicine, many hurdles hinder its incorporation into clinical practice, including but not limited to their sensitivity to differences in acquisition and reconstruction parameters. In this study, we evaluated the effects of differences in in-plane spatial resolution (IPR) on HRFs, using a phantom dataset (n = 14) acquired on two scanner models. Furthermore, we assessed the effects of interpolation methods (IMs), the choice of a new unified in-plane resolution (NUIR), and ComBat harmonization on the reproducibility of HRFs. The reproducibility of HRFs was significantly affected by variations in IPR, with pairwise concordant HRFs, as measured by the concordance correlation coefficient (CCC), ranging from 42% to 95%. The number of concordant HRFs (CCC > 0.9) after resampling varied depending on (i) the scanner model, (ii) the IM, and (iii) the NUIR. The number of concordant HRFs after ComBat harmonization depended on the variations between the batches harmonized. The majority of IMs resulted in a higher number of concordant HRFs compared to ComBat harmonization, and the combination of IMs and ComBat harmonization did not yield a significant benefit. Our developed framework can be used to assess the reproducibility and harmonizability of RFs.

Keywords: harmonization; image processing; radiomics biomarkers; reproducibility.

Purpose: To evaluate the choriocapillaris (CC) flow deficit (FD) beneath drusen associated with overlying intraretinal hyperreflective foci (HRF).

Methods: Patients with intermediate age-related macular degeneration (AMD) who had structural spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) using the Cirrus HD-OCT with AngioPlex software were retrospectively evaluated. A 6 × 6-mm-volume scan was used for the SD-OCT and OCTA. Post-imaging processing steps included generation of drusen map, identification of HRF, and generation of a signal-compensated CC slab prior to binarization and CC FD computation. The CC OCTA image was aligned with the drusen + HRF map to define regions of interest for CC FD measurement. The CC was quantified below drusen with and without overlying HRF and within a 150-μm-wide ring surrounding the drusen (unaffected by potential HRF-related shadowing), and across the entire 6 × 6 macular region.

Results: Fifty-three eyes with intermediate AMD were included, 25 eyes with HRF, and 28 eyes with no HRF. The mean ± SD FD% over the whole 6 × 6 macular region was 41.1 ± 3.4 in eyes with HRF compared with 39.5 ± 3.5 in eyes without HRF (p = 0.001). The mean ± SD CC FD% below drusen with HRF (54.4 ± 9.3) was significantly greater than below drusen without HRF (49.6 ± 9.5; p = 0.001). There was a strong positive correlation between the quantity of HRF and the extent of the CC FD (Pearson correlation = 0.81).

Conclusion: Choriocapillaris flow deficits appear to be more severe in eyes with HRF and in particular directly below HRF. As HRF are thought to represent a higher risk or more advanced feature of intermediate AMD, these findings highlight the relationship between the severity of CC FD and overall severity of AMD.

Keywords: Age-related macular degeneration; Choriocapillaris flow deficit; Hyperreflective foci.

Functional MRI (fMRI) is modeled as a convolution of the hemodynamic response function (HRF) and an unmeasured latent neural signal. However, HRF itself is variable across brain regions and subjects. This variability is induced by both neural and non-neural factors. Aberrations in underlying neurochemical mechanisms, which control HRF shape, have been reported in autism spectrum disorders (ASD). Therefore, we hypothesized that this will lead to voxel-specific, yet systematic differences in HRF shape between ASD and healthy controls. As a corollary, we also hypothesized that such alterations will lead to differences in estimated functional connectivity in fMRI space compared to latent neural space. To test these hypotheses, we performed blind deconvolution of resting-state fMRI time series acquired from large number of ASD and control subjects obtained from the Autism Brain Imaging Data Exchange (ABIDE) database (N = 1102). Many brain regions previously implicated in autism showed systematic differences in HRF shape in ASD. Specifically, we found that precuneus had aberrations in all HRF parameters. Consequently, we obtained precuneus-seed-based functional connectivity differences between ASD and controls using fMRI as well as using latent neural signals. We found that non-deconvolved fMRI data failed to detect group differences in connectivity between precuneus and certain brain regions that were instead observed in deconvolved data. Our results are relevant for the understanding of hemodynamic and neurochemical aberrations in ASD, as well as have methodological implications for resting-state functional connectivity studies in Autism, and more generally in disorders that are accompanied by neurochemical alterations that may impact HRF shape.

OBJECTIVE

To investigate the features of optic nerve head (ONH) microvasculature in primary open angle glaucoma using fractal geometry analysis.

METHODS

ONH blood flow was analyzed at the level of the lamina cribrosa by means of confocal scanning laser Heidelberg Doppler flowmetry (HRF) in medically-controlled early and advanced glaucoma. Fractal dimension D of vasculature map was calculated using the Box Counting.

RESULTS

Our data demonstrated that, in patients with advanced glaucoma, fractal dimension D was significantly lower than in controls, whereas, in the early stage of disease, its value was similar. Fractal dimension D of microcirculation was significantly and negatively correlated with the cup-disk area ratio in both early and advanced glaucoma groups, whereas linear cup-disk ratio of the disk, cup shape measure and nerve fiber layer thickness, where correlated only in advanced stage of the disease.

CONCLUSIONS

These findings demonstrate that fractal dimension D of ONH appeared significantly reduced in advanced glaucoma and correlated with the optic disc damage.