The steady increase of diabetes is becoming a major burden on health care systems. As diabetic complications arise from oxidative stress, an antioxidant therapy along with anti-diabetic drugs is recommended. Myrmecodia or ant plant is highly valued as a traditional medicine in West Papua. It is used as an alternative treatment for diabetes, as the substances produced by ants can reduce blood sugar levels. The aim of this study was to develop and establish high-performance thin-layer chromatographic (HPTLC)-bioautographic methods to measure the antioxidant and hypoglycemic effects in different extracts from Myrmecodia platytyrea and to compare them with sterol content. Antioxidant activity in methanol, ethanol, dichloromethane (DCM) and ethyl acetate (EA) extracts were measured with a direct HPTLC-2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) assay, while hypoglycemic effects were assessed using a newly developed α-amylase inhibitory activity assay. Stigmasterol is observed, after derivatization with anisaldehyde, as purple colored zones under visible light at hRF values of 0.66. The highest antioxidant activity was observed in the ethanol extract which is rich in polyphenols and flavonoids, while the DCM extract did not show antioxidant activity, but had significant α-amylase inhibitory activity. The highest α-amylase inhibitory activity was observed in the EA and DCM extracts and was related to their stigmasterol content.

Introduction: Metastasis-associated in colon cancer 1 (MACC1), one of the prognostic markers for colonic and other tumours was noted to be overexpressed in retinoblastoma (Rb) Y79 cancer stem cells. This prompted us to evaluate its expression in primary Rb tumour and serum samples with clinicopathologic correlation. The interacting partner, c-MET was also evaluated in primary tumour tissues to explore the activation of MACC1 signaling.

Methodology: This study was done following institutional review board approval from participating institutes. Semiquantitative gene expression for MACC1 was evaluated using formalin-fixed paraffin-embedded sections and unfixed tumour samples from primary Rb cases (n = 44). Immunolocalization for MACC1 was assessed in primary Rb tumours (n = 22), bone marrow aspirates with metastasis (n = 3), and c-MET expression was also assessed in Rb tumours (n = 17). Serum MACC1 levels were analysed using enzyme-linked immunosorbent assay in samples collected from Rb patients undergoing enucleation (n = 31), Rb patients with proven clinical metastasis (n = 3), and compared to appropriate controls. Clinicopathologic correlation of MACC1 expression was analysed using the medical records with specific reference to histologic risk factors (HRF) for metastasis and differentiation.

Results: High expression of MACC1 gene was noted in all the tumour samples (n = 44), more so in cases with versus without HRF (p < 0.0001). In cases with HRF, MACC1 and c-MET showed diffuse nuclear and cytoplasmic staining whereas it was predominantly cytoplasmic in cases without HRF. Mean immunoreactivity score of MACC1 and c-MET tissue immunolocalization revealed that cases with HRF showed significantly higher expression compared to cases without HRF (p < 0.05). Unlike the findings in colonic tumours, serum levels of MACC1 were lower in patients compared to normal controls.

Conclusion: Overexpression of MACC1 and c-MET in retinoblastoma tissues, specifically those with risk factors for metastasis, suggests its role in proliferation and possibly in invasion. However, the current data do not support it to be a clinical prognostic marker in retinoblastoma tumours. The inverse serum expression is an intriguing finding, which warrants further studies especially in retinoblastoma.

Keywords: Retinoblastoma; c-MET; histologic risk factor; metastasis; metastasis-associated in colon cancer 1.

Genetic fever syndromes or hereditary recurrent fever syndromes (HRF) are considered to be part of the autoinflammatory diseases (AID) which result from errors in the innate immune system. Patients typically have self-limiting episodes of fever and high levels of inflammation markers. The mode of inheritance is autosomal recessive or autosomal dominant. The diseases of the HRF include familial Mediterranean fever, tumor necrosis factor receptor 1-associated periodic syndrome, hyper-IgD syndrome and cryopyrin-associated periodic fever syndromes. The disease known as deficiency of interleukin 1 (IL1) receptor antagonist does not fully belong to this group because fever is not a typical symptom. The therapy depends on the type and severity of the disease. Effective prophylaxis is possible for FMF. Biologicals, especially IL1 blocking agents are highly effective in very severe fever syndromes. In order to collect more information on AID, to establish a biobank and coordinate research in this field the AID-Net project was founded. Currently 606 patients with AID are registered of whom 381 have HRF.

BACKGROUND

An application of scanning-laser ophthalmoscopic flowmetry, Heidelberg Retina Flowmetry (HRF) is reported to faithfully quantify retinal perfusion. Indeed, without convincing regard for the fact that the method produces numerical values for such so-called "VELOCITY" (and subsequently "calculates" "FLOW", and "VOLUME") with no physical units or proven real-life meaning, current clinical drug studies and patient care are being based on this method. To test the physical "fidelity" of the HRF method, the author hence devised a simple, reliable mechanical model to generate known velocities of movement of a test surface.

METHODS

Movement of the circumferential surface of an 89 mm (3 1/2-inch) Ø cylinder, belt-driven by a brass spindle with segments of increasing diameter, was "analyzed" with the HRF method. The true velocities (mm/sec) with which the surface passed the HRF's focal point were then determined using a stopwatch. A 10 degrees x 2.5 degrees measuring field and a 20 x 20-pixel analysis window were used. Measurements were made for horizontal, diagonal (45 degrees and 135 degrees), and vertical motion at all velocity settings of the model.

RESULTS

The relationship between real velocities of cylinder-surface motion and the corresponding HRF-"VELOCITY" values was nonlinear, an effect which increased significantly for diagonal and vertical motion.

CONCLUSIONS

Considering the dependency on orientation of motion and the non-linearity of the relationship between HRF results and true velocity, as well as several other weaknesses discussed herein, the question arises whether the validity of the HRF method should be reconsidered.

Background: Limited literature exists regarding whether intraoperative analysis of frozen debulk specimens during Mohs micrographic surgery (MMS) improves identification of high-risk features (HRF) of cutaneous squamous cell carcinoma (CSCC).

Objective: Primary: identification of new HRF on debulk specimens. Secondary: CSCC upstaged after considering debulk data.

Materials and methods: A single-center, retrospective cohort study of patients with biopsy-proven CSCC treated by MMS with intraoperative frozen debulk analysis. Restricted (poor differentiation, new perineural invasion ≥0.1 mm, and Breslow depth >6 mm) and nonrestricted (any worsened tumor differentiation, any new perineural invasion, and Breslow depth >2 mm) analyses were performed.

Results: In restricted analysis, 3.94% of cases had 1 new HRF on debulk analysis. In nonrestricted analysis, 32.9% of cases had ≥1 new HRF; 7.6% increased by 2 HRF. Approximately 2.0% of cases were upstaged by American Joint Committee on Cancer system, eighth edition criteria, 1.4% by Brigham and Women's Hospital. Tumor size ≥2 cm, male sex, and moderate differentiation on biopsy were significantly associated with new HRF identified on debulk analysis.

Conclusion: Intraoperative frozen debulk analysis can reveal HRF of CSCC not seen on biopsy or MMS stages, particularly among tumors ≥2 cm. American Joint Committee on Cancer system, eighth edition T2 tumors were most likely to be upstaged. Identification of new HRF on debulk analysis can improve CSCC staging and may impact patient treatment and follow-up.

Health-related fitness (HRF) and motor coordination (MC) can be influenced by children's environment and lifestyle behavior. This study evaluates the association between living environment and HRF, MC, and physical and sedentary activities of children in Suriname.

Tests were performed for HRF (morphological, muscular, and cardiorespiratory component), gross MC (Körperkoordinations Test für Kinder), fine MC (Movement Assessment Battery for Children), and self-reported activities in 79 urban and 77 rural 7-year-old Maroon children. Urban-rural differences were calculated by an independent sample t test (Mann-Whitney U test if not normally distributed) and χ2 test.

No difference was found in body mass index, muscle strength, and the overall score of gross and fine MC. However, urban children scored lower in HRF on the cardiorespiratory component (P ≤ .001), in gross MC on walking backward (P = .014), and jumping sideways (P = 0.011). They scored higher in the gross MC component moving sideways (P ≤ .001) and lower in fine MC on the trail test (P = .036) and reported significantly more sedentary and fewer physical activities than rural children.

Living environment was associated with certain components of HRF, MC, and physical and sedentary activities of 7-year-old children in Suriname. Further research is needed to evaluate the development of urban children to provide information for possible intervention and prevention strategies.

Conventional analysis of functional magnetic resonance imaging (fMRI) data using the general linear model (GLM) employs a neural model convolved with a canonical hemodynamic response function (HRF) peaking 5 s after stimulation. Incorporation of a further basis function, namely the canonical HRF temporal derivative, accounts for delays in the hemodynamic response to neural activity. A population that may benefit from this flexible approach is children whose hemodynamic response is not yet mature. Here, we examined the effects of using the set based on the canonical HRF plus its temporal derivative on both first- and second-level GLM analyses, through simulations and using developmental data (an fMRI dataset on proprioceptive mapping in children and adults). Simulations of delayed fMRI first-level data emphasized the benefit of carrying forward to the second-level a derivative boost that combines derivative and nonderivative beta estimates. In the experimental data, second-level analysis using a paired t-test showed increased mean amplitude estimate (i.e., increased group contrast mean) in several brain regions related to proprioceptive processing when using the derivative boost compared to using only the nonderivative term. This was true especially in children. However, carrying forward to the second-level the individual derivative boosts had adverse consequences on random-effects analysis that implemented one-sample t-test, yielding increased between-subject variance, thus affecting group-level statistic. Boosted data also presented a lower level of smoothness that had implication for the detection of group average activation. Imposing soft constraints on the derivative boost by limiting the time-to-peak range of the modeled response within a specified range (i.e., 4-6 s) mitigated these issues. These findings support the notion that there are pros and cons to using the informed basis set with developmental data.

Functional MRI studies have started the hemodynamic responses of the placenta and fetal brain using maternal hyperoxia. While most studies have focused on analyzing the changes in magnitude of fMRI signals, few studies have analyzed the latency and duration of responses to hyperoxia. This paper proposes a linear convolution model of fetal circulation where a chain of responses to maternal hyperoxia are produced in the placenta and fetal brain. Specifically, an impulse response to hyperoxia was modeled as the hemodynamic response function (HRF) which consists of multiple gamma functions. Both time-to-peak and full width at half maximum of HRF were estimated using simulated annealing (SA). A Monte Carlo simulation was carried out to evaluate the performance of the SA-based method for estimating both parameters. Finally, we provided an example of estimating HRFs from fMRI time series of the placenta and fetal brain acquired during maternal hyperoxia in vivo.

We demonstrate that high-quality interference filters for the wavelength range 1300-1600 nm can be holographically fabricated in DuPont HRF-800X001 photopolymer material by use of visible laser illumination. We also summarize a chain-matrix technique, which we call thin-film decomposition, that is useful for modeling multilayer films with an arbitrary index profile n(z). We use the thin-film-decomposition technique to create design curves that allow one to choose the proper exposure angle and film thickness with which to fabricate a holographic interference filter with a desired transmission efficiency and bandwidth at a particular wavelength. These curves are of general utility and are not confined to any particular holographic recording medium. Excellent agreement between theory and experiment is found.

In a penicillin-allergic patient who showed a strong dual skin reaction (immediate and late components) to an intradermal injection of the antigen, we investigated the possibility that the lymphokine, histamine-releasing factor (HRF), which has been shown to release histamine from human basophils and mast cells, might play a part in the elicitation of the late phase of the 'dual reaction'. In vitro stimulation of this patient's lymphocytes, but not those of a patient with a monophasic (immediate) reaction with the antigen, caused the production of a large amount of HRF, while a moderate lymphoproliferation occurred in both patients. The purified HRF released histamine from the patient's own leucocytes and also caused immediate wheal and flare reaction on intradermal injection.

Human Basophil Degranulation Test (HBDT) has been employed for the research of Histamine Releasing Factor (HRF) from macrophages in asthma. Macrophages have been obtained from broncho-alveolar lavages, incubated with specific allergens and the products of this stimulation added to HBDT preparations. The production of an active HRF has been observed only in macrophages from atopic patients. The effect of this HRF seems to be IgE dependent, the degranulation of human basophils being in general significant only for basophils of atopic patients.

OBJECTIVE

To identify the investigator effect in the analysis results of Heidelberg retinal flowmetry (HRF) images when pixel-by-pixel analysis is performed.

METHODS

Thirty-two of 732 HRF images were randomly selected from a population-based study. Pixel-by-pixel analysis was performed by two trained masked graders in the following way: a square window of 40 x 40 pixels or two windows of 30 x 30 pixels or four windows of 20 x 20 pixels free from blood vessels at the peripapillary retina were identified. Using a 1 x 1-pixel window, the grader performed pointwise analysis according to a specific protocol. The analysis process was performed by each observer three times (A, B, C) at 1-week intervals. The percentage of pixels with < 1 arbitrary unit of flow (zero flow), the 10th, 25th, 50th, 75th and 90th percentiles and mean flow values were calculated. The difference between the results of analyses B-A and C-A for all HRF parameters was estimated using the Wilcoxon signed rank test. Mixed-effect regression models were also used after controlling for grader effect and correlation within subjects.

RESULTS

There was no statistically significant difference between the results of analyses B-A and C-A or for any parameter in the mixed-effect regression models. Intraclass correlation was 0.9665 for the percentage of zero flow pixels.

CONCLUSIONS

Pixel-by-pixel analysis of HRF images by trained graders remains a highly reproducible method. No grader effect was found. If a precise protocol is followed, the results are independent of the exact placement of the analysis windows and the pointwise analysis of the identified and mapped retinal tissue.

OBJECTIVE

To determine the effects of heart rate frequency (HRF) and heart rate variability (HRV) on radiation exposure and image quality in a large cohort of patients undergoing DSCT (dual-source computed tomograph) coronary angiography with three different electrocardiogram (ECG) pulsing models, to prospectively investigate CT image quality parameters by using different protocols and to calculate the radiation dose estimates for noninvasive coronary angiography performed by DSCT.

METHODS

Over a 1-month period, 253 consecutive patients were recruited and categorized into 3 groups: Group A:low HRF (≤ 75 beats/min) with normal-minor heart rate variability (HRV) (mean interbeat difference (IBD), 0 - 3), coronary CT angiography proceeding with prospective ECG-triggered flash spiral scan; Group B: intermediate-high HRF >> 75 beats/min) with normal-minor HRV (IBD, 0 - 4), with prospective ECG-triggered sequence scan; Group C: intermediate-high HRF >> 75 beats/min) with moderate-severe HRV (IBD ≥ 5) with retrospective ECG-gated spiral scan.

RESULTS

CT coronary angiography yielded excellent image quality in 87.7% of patients (222/253). No significant differences were found among three groups with different HRF and HRV in image quality and diagnostic performance. Radiation exposure was significantly higher in patients with low versus high HRF and in patients with severe versus normal HRV. Significant difference (P < 0.001) was found among the effective doses of group A (mean ± standard deviation, 0.602 ± 0.363 mSv), group B (1.253 ± 0.804 mSv) and group C (9.039 ± 5.657 mSv).

CONCLUSIONS

The higher temporal resolution of dual-source spiral CT coronary angiography performed with adaptive ECG pulsing results in preserved diagnostic image quality and performance independent of HRF or HRV at the cost of limited dose reduction in arrhythmic patients.

For many biophysical systems, direct measurement of all state-variables, in-vivo is not-feasible. Thus, a key challenge in biological modeling and signal processing is to reconstruct the activity and structure of interesting biological systems from indirect measurements. These measurements are often generated by approximately linear time-invariant (LTI) dynamical interactions with the hidden system and may therefore be described as a convolution of hidden state-variables with an unknown kernel. In the current work, we present an approach termed surrogate deconvolution, to directly identify such coupled systems (i.e. parameterize models). Surrogate deconvolution reframes certain nonlinear partially-observable identification problems, which are common in neuroscience/biology, as analytical objectives that are compatible with almost any user-chosen optimization procedure. We show that the proposed technique is highly scalable, low in computational complexity, and performs competitively with the current gold-standard in partially-observable system estimation: the joint Kalman Filters (Unscented and Extended). We show the benefits of surrogate deconvolution for model identification when applied to simulations of the Local Field Potential and blood oxygen level dependent (BOLD) signal. Lastly, we demonstrate the empirical stability of Hemodynamic Response Function (HRF) kernel estimates for Mesoscale Individualized NeuroDynamic (MINDy) models of individual human brains. The recovered HRF parameters demonstrate reliable individual variation as well as a stereotyped spatial distribution, on average. These results demonstrate that surrogate deconvolution promises to enhance brain-modeling approaches by simultaneously and rapidly fitting large-scale models of brain networks and the physiological processes which generate neuroscientific measurements (e.g. hemodynamics for BOLD fMRI).

Keywords: Deconvolution; Dual Estimation; Model Fitting; fMRI.

Hemodynamic Response Function (HRF) estimation in functional Magnetic Resonance Imaging (fMRI) experiments is an important issue in functional neuroimages analysis. Indeed, when modeling each brain region as a stationary linear system characterized by its impulse response, the HRF describes the temporal dynamic of the brain region response during activations. Using the mixed-effects model, a new algorithm for maximum likelihood HRF estimation is derived. In this model, the random effect is used to better account for the variability of the drift. Contrary to the usual approaches, the proposed algorithm has the benefit of considering an unknown drift matrix. Estimations of the HRF and the hyperparameters are derived by alternating minimization of the Kullback-Leibler divergence between a model family of probability distributions defined using the mixed-effects model and a desired family of probability distributions constrained to be concentrated on the observed data. The relevance of proposed approach is demonstrated both on simulated and real data.

Oil-grit separators (OGSs) are one type of best management practice, designed to remove oil and grit from stormwater runoff (e.g., from parking lots and paved roads). This note examines scaling parameters for OGS removal efficiency. Three dimensionless parameters are chosen as scaling parameters: Hazen number (Ha), Reynolds number (Re) and Froude number (Fr). The Hazen number is a ratio of hydraulic residence time to particle settling time. The Reynolds number measures the surrounding turbulence effects on sediment removal efficiency. The Froude number represents the ratio of inertial and gravitational forces, which indicates the influence of gravity on fluid motion. The collected data from the literature on sediment removal in OGSs can be represented by a single curve when the Hazen, Reynolds, and Froude numbers are combined into a new scaling parameter (HRF = Ha(Re/Fr)). A general form is proposed to correlate the sediment removal efficiency with this new parameter. This generalized prediction method can be used as a preliminary performance indicator for OGS units. The obtained curve can also be used to adjust raw laboratory and field measurement data to improve the evaluation of the performance of various OGSs.

Several dynamical aspects of the DuPont photopolymer film HRF-150-38 for holographic storage are described. We study temporal aspects of exposure, exposure time, processing situations, and storage effect. The quantities studied are diffraction efficiencies, thickness changes, and Bragg angle. The experimental results are performed with an argon-ion laser at 514.5 nm.

A human histamine releasing lymphokine (histamine releasing factor, HRF) was studied for its ability to release slow reacting substance (SRS) alongside histamine from human leucocytes. HRF was found to release a substantial amount of SRS from human leucocytes. The SRS was identified by its slow contraction of isolated guinea pig ileum preparation in the presence of atropine and mepyramine, inhibition of this action by the SRS antagonist FPL 55712, the inhibition of its production by eicosa--5, 8, 11, 14--tetraynoic acid (ETYA) but not indomethacin, and a final confirmation by a radioimmunoassay for leukotriene C4 (LTC4). Amounts of SRS ranging from a few nanograms to about 180 ng (eqt LTD4) could be released from 10(8) leucocytes depending on the dose of HRF, and there is a good correlation between the amount of SRS produced and the percentage histamine release accompanying it. These findings suggest that the human lymphokine (HRF) may play an important role in acute hypersensitivity and inflammatory reactions in addition to its traditional role as mediator of delayed hypersensitivity reactions.

The pathogenesis of asthma can be divided into clinical, physiological, and anatomical considerations. Clinical features include reversible obstruction, allergens, and other factors such as gastroesophageal reflux. Physiological considerations include bronchial hyperreactivity, neurologic abnormalities, nonadrenergic noncholinergic system (NANC), and neuropeptides. Anatomic and cellular considerations include eosinophils, respiratory epithelium, mast cells/basophils, cytokines, and histamine-releasing factors (HRF), and histamine-release inhibitory factor (HRIF).

Recently monocyte chemotactic and activating factor (MCAF) has been reported to be a potent histamine releasing factor (HRF) for human basophils. In this study we investigated the localization and biological activity of MCAF in human nasal mucosa. To investigate the localization of MCAF within the nasal mucosa we performed specific immunohistochemical staining of sections of large pieces of the inferior turbinate obtained by conchotomy from patients with nasal allergy and without nasal allergy and compared them. Sections of nasal mucosa from allergic subjects stained with anti-MCAF mAb demonstrated the presence of many MCAF-positive cells in the lamina propria especially around small vessels and excretory gland, but only a few positive cells were found in the nasal mucosa of normal subjects. We cultured allergic nasal mucosa and sinus mucosa from patients with chronic inflammation for 2 days and detected MCAF by western blot analysis of the culture supernatants. One portion separated from sinus mucosa supernatant by column chromatography also released histamine from human basophils. Mean release was 3-4% and the difference from the control was statistically significant (p < 0.05). In the human nasal mucosa it seemed to exist IgE independent histamine releasing system sustained by MCAF producing cells. These results suggested that MCAF is one of the important mediators causing histamine release in the late phase reaction and in protracted inflammation of the nasal mucosa.

The present concepts on histamina releasing factors are discussed, their cellular origins, their effect on the target cells and its importance in asthma immunopathology. Personal results on the production of HRF by alveolar macrophages stimulated by allergen and its action on non atopic basophils are presented. Alveolar macrophages from atopic asthmatics release HRF in presence of allergen. Macrophage from non atopic do not. HRF has been tested in a Human Basophil Degranulation Test (HBDT) preparation, a significant degranulation induced by HRF from atopic patient being only observed when atopic basofils are used in HBDT. These results confirm that allergen could induce HRF production from alveolar macrophages and that this HRF could degranulate basophils in atopic and induce mediators release.

Different methods of the preparation of haemorrhagic fever with renal syndrome (HFRS) antigen for complement-fixation (CF) test are described. The antigens were prepared from the organs of suckling white rats inoculated with the Western type of HRFS by precipitation with polyethylene glycol, by fluorocarbon treatment and or by sucrose-acetone extraction. The highest CF titre was obtained by acetone precipitation of 20% brain suspension in isotonic sucrose.