Translationally controlled tumor protein (TCTP), also known as histamine releasing factor (HRF), is found abundantly in different eukaryotic cell types. The sequence homology of TCTP between different species is very high, belonging to the MSS4/DSS4 superfamily of proteins. TCTP is involved in both cell growth and human late allergy reaction, as well as having a calcium binding property; however, its primary biological functions remain to be clearly elucidated. In regard to many possible functions, the TCTP of Plasmodium falciparum (Pf) is known to bind with an antimalarial agent, artemisinin, which is activated by heme. It is assumed that the endoperoxide-bridge of artemisinin is opened up by heme to form a free radical, which then eventually alkylates, probably to the Cys14 of PfTCTP. Study of the docking of artemisinin with heme, and subsequently with PfTCTP, was carried out to verify the above hypothesis on the basis of structural interactions. The three dimensional (3D) structure of PfTCTP was built by homology modeling, using the NMR structure of the TCTP of Schizosaccharomyces pombe as a template. The quality of the model was examined based on its secondary structure and biological function, as well as with the use of structure evaluating programs. The interactions between artemisinin, heme and PfTCTP were then studied using the docking program, FlexiDock. The center of the peroxide bond of artemisinin and the Fe of heme were docked within a short distance of 2.6A, implying the strong possibility of an interaction between the two molecules, as proposed. When the activated form of artemisinin was docked on the PfTCTP, the C4-radical of the drug faced towards the sulfur of Cys14 within a distance of 2.48A, again suggesting the possibility of alkylation having occurred. These results confirm the proposed mechanism of the antimalarial effect of artemisinin, which will provide a reliable method for establishing the mechanism of its biological activity using a molecular modeling study.

Cervical cancer is currently the first or second leading cause of cancer-related mortality among women in developing countries. This study was conducted in order to determine whether neoadjuvant cisplatin and 5-flourouracil (NAPF) prior to surgery is superior to primary surgical treatment (PST) as a treatment option for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2/IIA2 cervical cancer. A retrospective review of 195 patients with early-stage bulky cervical cancer was performed. The patients were divided into two groups, according to whether they received NAPF prior to surgery. The surgical profiles and complications, risk factors of recurrence and survival were compared between the groups. The response rate to NAPF was found to be 61.2%. There were no differences in operative time and intra-operative complications between the two groups, whereas the estimated blood loss in the NAPF and PST groups were 620.1±394.9 and 434.8±233.7 ml, respectively (P=0.000). When compared with PST, NAPF remarkably reduced tumor size (22.5 vs. 93.3%, P=0.000). Furthemore, the ratio of deep stromal invasion was significantly lower in responders to NAPF compared with that in non-responders (46.7 vs. 76.3%, respectively; P=0.004) and in the PST group (46.7 vs. 70.0%, respectively; P=0.004). No reduction of high-risk factors (HRFs) was observed. The NAPF group, even the responder subgroup, exhibited no significant improvement in progression-free survival (PFS) and overall survival (OS) compared to the PST group. In conclusion, despite the reduction of intermediate-risk factors (IRFs), neoadjuvant chemotherapy (NAC) with the NAPF regimen prior to radical surgery (RS) did not improve the prognosis in patients with FIGO stage IB2/IIA2 cervical cancer.

Purpose: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of optical coherence tomography (OCT) scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD), and make the raw segmentation output data openly available for further research.

Design: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.

Participants: 2473 first-treated eyes and another 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017.

Methods: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first and second eyes, by visual acuity (VA) and by race/ethnicity, and correlations between volumes.

Main outcome measures: Volumes of segmented features (mm³), central subfield thickness (CST) (μm).

Results: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED and SRF. Eyes from black individuals had higher SRF, RPE and serous PED volumes, compared with other ethnic groups. Greater volumes of the vast majority of features were associated with worse VA.

Conclusion: We report the results of large scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care, and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

BACKGROUND

Hypoxemia is associated with worse outcomes in COPD. The aim of the study was to investigate the prevalence, incidence, and risk factors of hypoxic respiratory failure (HRF) in COPD.

METHODS

This was a longitudinal analysis of data from the Swedish National Register of COPD. HRF was defined as resting saturation ≤88% or long-term oxygen therapy. Risk factors for developing HRF were analyzed using multiple logistic regression and receiver operating characteristic curve analysis.

RESULTS

A total of 3,061 patients were included; mean forced expiratory volume in 1 second was 1.47 L; mean age was 70 years; and 54% were females. Median follow-up time was 1.8 years (interquartile range 1.3-2.4 years). HRF was present in 43 (1.4%) patients at baseline and 74 (2.4%) patients at follow-up. Among patients without HRF at baseline, 49 (1.6%) developed HRF during follow-up. The risk was highest for patients in Global initiative for Chronic Obstructive Lung Disease (GOLD) 2017 stage IV or groups C or D at baseline. Developing HRF was independently predicted by lower forced expiratory volume in 1 second and lower COPD Assessment Test score, with a c-statistic of 0.84 (95% CI, 0.70-0.91). When the multivariable model used the GOLD 2017 variables stages I-IV and the dichotomized variables frequent exacerbations and COPD Assessment Test ≥10; the c-statistic increased slightly to 0.86 (95% CI, 0.80-0.92; P<0.0001).

CONCLUSIONS

In patients with COPD, the prevalence and incidence of HRF was low and was predicted well by more severe air flow limitation and worse health status. The risk is highest in patients with GOLD stage IV and GOLD groups C or D.

The haemodynamic response function (HRF) is a key component of the blood oxygen level-dependent (BOLD) signal, providing the mapping between neural activity and the signal measured with functional magnetic resonance imaging (fMRI). Most of the time the HRF is associated with task-based fMRI protocols, in which its onset is explicitly included in the design matrix. On the other hand, the HRF also mediates the relationship between spontaneous neural activity and the BOLD signal in resting-state protocols, in which no explicit stimulus is taken into account. It has been shown that resting-state brain dynamics can be characterized by looking at sparse BOLD 'events', which can be retrieved by point process analysis. These events can be then used to retrieve the HRF at rest. Crucially, cardiac activity can also induce changes in the BOLD signal, thus affecting both the number of these events and the estimation of the haemodynamic response. In this study, we compare the resting-state haemodynamic response retrieved by means of a point process analysis, taking the cardiac fluctuations into account. We find that the resting-state HRF estimation is significantly modulated in the brainstem and surrounding cortical areas. From the analysis of two high-quality datasets with different temporal and spatial resolution, and through the investigation of intersubject correlation, we suggest that spontaneous point process response durations are associated with the mean interbeat interval and low-frequency power of heart rate variability in the brainstem.

Following the detection of histamine-releasing activity (HRA) in the supernatants of peripheral blood mononuclear cell cultures, research efforts were directed at characterizing the source of this activity, mostly focusing, on IgE-dependent histamine-releasing factors (HRFs). HRF is now variously called translationally controlled tumor protein (TCTP), p21, p23, and fortilin. TCTP exhibits cytokine-like functions including release of histamine, induction of TH2 cytokines and chemoattractants, augmentation of B cell proliferation, and immunoglobulin production during late phase allergic inflammation. Because of its association with the allergic status of patients, TCTP emerged as a potential key agent in the modulation of allergic diseases. Several lines of evidence suggest that TCTP exhibits its cytokine-like functions only after it is modified by the proteases, altered oxidant-antioxidant balance and immunoglobulin E, present in the inflamed sites. This review will try to show that dimerization is the critical modification of TCTP if not the only modification, responsible for its cytokine-like activity causing allergic diseases.

OBJECTIVE

This study validated the laboratory testing used to monitor on water training. The purpose was to test that reference heart rates (HR) determined during an incremental test elicit comparable blood lactate levels ([La](b)) during a 30 min on water rowing.

METHODS

Blood lactate profile were determined during incremental graded exercise in 14 national and international level oarsmen. The HR corresponding to [La](b) of 2 and 3 mmol x l(-1) were determined (HRLa2 and HRLa3 respectively). The rowers then performed a 30 min training session in a boat. Training intensity, as assessed by HR monitors, had to range between HRLa2 and HRLa3. Field [La](b) (Laf) and HR (HRf) were measured at the end of the training session.

RESULTS

Laf was 2.13+/-0.49 mmol x l(-1) (range: 1.43-3.07) and did not differ significantly from 2 mmol x l(-1). HRf (162+/-7.4 beats x min(-1)) ranged from HRLa2 (159+/-9.5 beats x min(-1)) to HRLa3 (171+/-9 beats x min(-1)). HRf was not significantly different from HRLa2.

CONCLUSIONS

It was concluded that the HR determined during the laboratory testing are valid for monitoring on water training in highly trained rowers.

OBJECTIVE

(a) To show that high-altitude retinopathy (HAR) is common at high altitudes even in well-acclimatised climbers and that it should not be regarded as part of the spectrum of benign mountain sickness but rather as a clinical sign with a separate aetiology. (b) To test the hypothesis that HAR could be interpreted as a clinical expression of 'ocular vascular dysregulation'.

METHODS

Both eyes of the 8 mountaineers of the First Vienna Himalayan Expedition in May/June 1996 were examined 2 weeks before departure to and 2 weeks after descent from a high altitude. Retinal blood flow was measured in the right eyes of 7 climbers, using the Heidelberg Retina Flowmeter (HRF).

RESULTS

Two of the 8 climbers had bilateral retinal haemorrhage after the expedition. In 5 climbers chronic hypoxic exposure caused an increase in retinal blood flow between +18% and +96%, and in 2 climbers a decrease in retinal blood flow between -21% and -31%. The 2 climbers (climbers 1 and 2) with bilateral retinal haemorrhage showed a significant increase in HRF parameters.

CONCLUSIONS

HAR may be a clinical sign of mountaineers with a tendency towards ocular vascular dysregulation. The pronounced increase in all haemodynamic parameters in the 2 climbers with retinal haemorrhage combined with a dilated epipapillary network 2 weeks after the exposure reflects a retinal vessel configuration, as might be expected at high altitudes under acute hypoxic stress. An inadequate autoregulatory response of the retinal circulation under conditions of chronic hypoxia may play an important part in the pathogenesis of HAR.

Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences.

fMRI, one of the most important noninvasive brain imaging methods, relies on the blood oxygen level-dependent (BOLD) signal, whose precise underpinnings are still not fully understood. It is a widespread assumption that the components of the hemodynamic response function (HRF) are fixed relative to each other in time, leading most studies as well as analysis tools to focus on trial-averaged responses, thus using or estimating a condition- or location-specific "canonical HRF". In the current study, we examined the nature of the variability of the BOLD response and asked in particular whether the positive BOLD peak is subject to trial-to-trial temporal jitter. Our results show that the positive peak of the stimulus-evoked BOLD signal exhibits a trial-to-trial temporal jitter on the order of seconds. Moreover, the trial-to-trial variability can be exploited to uncover the initial dip in the majority of voxels by pooling trial responses with large peak latencies. Initial dips exposed by this procedure possess higher spatial resolution compared to the positive BOLD signal in the human visual cortex. These findings allow for the reliable observation of fMRI signals that are physiologically closer to neural activity, leading to improvements in both temporal and spatial resolution.

Technical developments in MRI have improved signal to noise, allowing use of analysis methods such as Finite impulse response (FIR) of rapid event related functional MRI (er-fMRI). FIR is one of the most informative analysis methods as it determines onset and full shape of the hemodynamic response function (HRF) without any a priori assumptions. FIR is however vulnerable to multicollinearity, which is directly related to the distribution of stimuli over time. Efficiency can be optimized by simplifying a design, and restricting stimuli distribution to specific sequences, while more design flexibility necessarily reduces efficiency. However, the actual effect of efficiency on fMRI results has never been tested in vivo. Thus, it is currently difficult to make an informed choice between protocol flexibility and statistical efficiency. The main goal of this study was to assign concrete fMRI signal to noise values to the abstract scale of FIR statistical efficiency. Ten subjects repeated a perception task with five random and m-sequence based protocol, with varying but, according to literature, acceptable levels of multicollinearity. Results indicated substantial differences in signal standard deviation, while the level was a function of multicollinearity. Experiment protocols varied up to 55.4% in standard deviation. Results confirm that quality of fMRI in an FIR analysis can significantly and substantially vary with statistical efficiency. Our in vivo measurements can be used to aid in making an informed decision between freedom in protocol design and statistical efficiency.

Plants undergo changes in response to biotic and abiotic stresses that help them adjust and survive. Some of these changes may even be passed on to progeny and eventually lead to adaptive evolution. Transgenerational changes in response to stress include alterations in DNA methylation and changes in homologous recombination frequency (HRF). The progeny of plants that were stressed often show elevated HRF as well as genomic hypermethylation, although specific loci that are beneficial in times of stress may be hypomethylated. One of the possible mechanisms responsible for passing the memory to the progeny involves small interfering RNAs; Dicer-like proteins, DCL2 and DCL3, are in part required for this process. However, while epigenetic modifications are often present in the untreated progeny of stressed plants, they are not usually sustained for multiple unexposed generations. Still, transgenerational inheritance of such changes has already begun to provide evidence for an important role of epigenetics in enhancing stress resistance.

OBJECTIVE

People with chronic hypercapnic respiratory failure (HRF) often have a ventilatory limitation to exercise with difficulty performing activities of daily living. Although non-invasive ventilation (NIV) appears to reduce the ventilatory limitation and improve exercise performance in people with severe COPD, the effect of NIV during functional activities such as unsupported arm exercise (UAE) and ground walking in people with chronic HRF is unclear.

METHODS

Seventeen patients with chronic HRF (PaCO(2) 52.1 +/- 5.3 mm Hg) performed a series of UAE tests, and 15 patients (PaCO(2) 51.7 +/- 3.8 mm Hg) performed a series of endurance shuttle walk tests, with and without NIV in a randomized cross-over design.

RESULTS

NIV during UAE increased endurance time by a mean of 91 s (95% confidence interval (CI): 10-172, P = 0.031) and reduced dyspnoea by a mean of 2.3 on the Borg scale (95% CI: 1.0-3.7, P = 0.002) compared with exercise without NIV. There was a non-significant increase in walking endurance time with NIV during exercise (119 s, 95% CI: -17 to 254, P = 0.081); however, isotime dyspnoea was unchanged compared with walking without NIV (-1.0, 95% CI: -3.0 to 1.0, P = 0.29).

CONCLUSIONS

NIV during UAE increased endurance time and reduced dyspnoea compared with exercise without NIV in patients with chronic HRF. Investigation of the role of NIV as an adjunct to UAE training is warranted. In contrast, NIV during ground walking did not improve exercise capacity. However, the pressure support provided may have been inadequate as dyspnoea was not reduced.

OBJECTIVE

The purpose of this study was to determine the extent to which a sport education season of fitness could provide students with recommended levels of in-class moderate-to-vigorous physical activity (MVPA) while also increasing students' fitness knowledge and fitness achievement.

METHODS

One hundred and sixty-six 5th-grade students (76 boys, 90 girls) participated in a 20-lesson season called "CrossFit Challenge" during a 4-week period. The Progressive Aerobic Cardiovascular Endurance Run, push-ups, and curl-ups tests of the FITNESSGRAM® were used to assess fitness at pretest and posttest, while fitness knowledge was assessed through a validated, grade-appropriate test of health-related fitness knowledge (HRF). Physical activity was measured with Actigraph GT3X triaxial accelerometers.

RESULTS

Results indicated a significant time effect for all fitness tests and the knowledge test. Across the entire season, the students spent an average of 54.5% of lesson time engaged in MVPA, irrespective of the type of lesson (instruction, free practice, or competition).

CONCLUSIONS

The results suggest that configuring the key principles of sport education within a unit of fitness is an efficient model for providing students with the opportunity to improve fitness skill and HRF knowledge while attaining recommended levels of MVPA.

OBJECTIVE

To evaluate the use of the Heidelberg retina flowmeter (HRF) in diagnosing retinal ischaemia following macular branch retinal vein occlusion.

METHODS

Ten patients with ischaemic macular branch retinal vein occlusion, as determined by strict fluorescein angiographic criteria, were examined with the HRF. Blood flow, blood volume and blood velocity characteristics from areas of ischaemic and non-ischaemic retina were recorded and the results between the normal and ischaemic areas of retina compared with paired t-test analysis. Ten healthy volunteers were similarly examined and acted as a control group.

RESULTS

Compared with normal retina the HRF recorded a statistically significant reduction in blood flow within the ischaemic retina in 7 of the 10 study patients. In 2 patients the HRF actually recorded a statistically significant increase in blood flow in the area of ischaemic retina; there was no significant difference in the blood flow recorded in the normal and ischaemic retina in the remaining patient. HRF examination of the control group revealed a significant difference in the blood flow between two areas of apparently normal retina in 3 of the 10 volunteers.

CONCLUSIONS

The HRF is not a reliable tool for diagnosing retinal ischaemia following branch retinal vein occlusion. Our results may suggest that the HRF blood flow recordings are not derived from the retinal circulation alone, but represent the cumulative blood flow through the combined circulations of the retina and choriocapillaris.

In this paper we present a procedure to retrieve the hemodynamic response function (HRF) from resting state functional magnetic resonance imaging (fMRI) data. The fundamentals of the procedures are further validated by considering simultaneous electroencephalographic (EEG) recordings. The typical HRF shape at rest for a group of healthy subject is presented. Then we present the modifications to the shape of the HRF at rest following two physiological modulations: eyes open versus eyes closed and propofol-induced modulations of consciousness.

OBJECTIVE

There is an established link between health-related functioning (HRF) and cardiovascular disease (CVD) mortality, and it is known that those with diabetes predominantly die of CVD. However, few studies have determined the combined impact of diabetes and impaired HRF on CVD mortality. We investigated whether this combination carries a higher CVD risk than either component alone.

METHODS

The Australian Diabetes, Obesity and Lifestyle (AusDiab) study included 11,247 adults aged ≥ 25 years from 42 randomly selected areas of Australia. At baseline (1999-2000), diabetes status was defined using the World Health Organization criteria and HRF was assessed using the SF-36 questionnaire.

RESULTS

Overall, after 7.4 years of follow-up, 57 persons with diabetes and 105 without diabetes had died from CVD. In individuals with and without diabetes, HRF measures were significant predictors of increased CVD mortality. The CVD mortality risks among those with diabetes or impaired physical health component summary (PCS) alone were similar (diabetes only: hazard ratio 1.4 [95% CI 0.7-2.7]; impaired PCS alone: 1.5 [1.0-2.4]), while those with both diabetes and impaired PCS had a much higher CVD mortality (2.8 [1.6-4.7]) compared with those without diabetes and normal PCS (after adjustment for multiple covariates). Similar results were found for the mental health component summary.

CONCLUSIONS

This study demonstrates that the combination of diabetes and impaired HRF is associated with substantially higher CVD mortality. This suggests that, among those with diabetes, impaired HRF is likely to be important in the identification of individuals at increased risk of CVD mortality.

This research describes a new Bayesian spatiotemporal model to analyse BOLD fMRI studies. In the temporal dimension, we describe the shape of the hemodynamic response function (HRF) with a transfer function model. The spatial continuity and local homogeneity of the evoked responses are modelled by a Gaussian Markov random field prior on the parameter indicating activations. The proposal constitutes an extension of the spatiotemporal model presented in a previous approach [Quirós, A., Montes Diez, R. and Gamerman, D., 2010. Bayesian spatiotemporal model of fMRI data, Neuroimage, 49: 442-456], offering more flexibility in the estimation of the HRF and computational advantages in the resulting MCMC algorithm. Simulations from the model are performed in order to ascertain the performance of the sampling scheme and the ability of the posterior to estimate model parameters, as well as to check the model sensitivity to signal to noise ratio. Results are shown on synthetic data and on a real data set from a block-design fMRI experiment.

Brain oscillations and synchronicity among brain regions (brain connectivity) have been studied in resting-state (RS) and task-induced settings. RS-connectivity which captures brain functional integration during an unconstrained state is shown to vary with the frequency of oscillations. Indeed, high temporal resolution modalities have demonstrated both between and cross-frequency connectivity spanning across frequency bands such as theta and gamma. Despite high spatial resolution, functional magnetic resonance imaging (fMRI) suffers from low temporal resolution due to modulation with slow-varying hemodynamic response function (HRF) and also relatively low sampling rate. This limits the range of detectable frequency bands in fMRI and consequently there has been no evidence of cross-frequency dependence in fMRI data. In the present work we uncover recurring patterns of spectral power in network timecourses which provides new insight on the actual nature of frequency variation in fMRI network activations. Moreover, we introduce a new measure of dependence between pairs of rs-fMRI networks which reveals significant cross-frequency dependence between functional brain networks specifically default-mode, cerebellar and visual networks. This is the first strong evidence of cross-frequency dependence between functional networks in fMRI and our subject group analysis based on age and gender supports usefulness of this observation for future clinical applications.

The aim of this study was: echocardiographical assessment of cardiac alterations in late-preterm newborns with hypoxic respiratory failure (HRF), and, study serum pentraxin-3 (PTX-3) in relation to the severity of respiratory impairment and to some echocardiographic parameters (i.e. ejection fraction (EF), stroke volume (SV) and cardiac output (CO). We enrolled in this study 40 newborn infants whose 22 (group I) with moderate HRF and 18 (group II) with severe HRF. In group I the mean values of EF, SV and CO were significantly higher than in the group II. Our results showed a significant increase of PTX-3 in group II patients at 24h of life when compared to group I. Taking patients all together (n=40), we found a significant (R=-73) reverse correlation between EF and serum values of PTX-3. PTX-3 in our patients with HRF is affected by the severity of the hypoxic insult and correlate with the cardio-vascular impairment.

In retinoblastoma, adjuvant chemotherapy after enucleation is given in eyes with histopathological high-risk features (HRFs) to reduced mortality. Anterior chamber seeds (AC seeds) on histopathological evaluation are a contentious finding. This study attempts to determine the effect of AC seeds on the survival rate.

This is a retrospective case record review. Eyes were divided into four groups: those with neither AC seeds nor HRFs, those with only HRFs, those with only AC seeds, and those with both HRFs and AC seeds. The groups were compared for demographic and clinical features and survival curves were plotted for each.

For the 212 eyes included in the study, mean age was 30.5 ± 36.8 months. Children with only AC seeds were significantly older (75.3 ± 94.6 months) (P = 0.004). Chemotherapy was administered in 81 (38.2%) of 212 eyes; 16 (13.7%) of 117 eyes without HRF and in 65 (68.4%) of 95 eyes with HRFs (P < 0.001). The survival rate at 1, 3, and 5 years was the highest for the group with only AC seeds, although the difference was not statistically significant.

We conclude that AC seeds do not, by themselves, constitute an independent risk factor for metastasis. These children need not be treated with immediate adjuvant chemotherapy, but, instead, can be followed with regular screening for metastasis. However, AC seeds are seen in only a small proportion of enucleated eyes. A larger study would better validate our study results.

To delineate the working mechanisms of immunotherapy (IT) (hyposensitization), the production of, and responsiveness to, histamine-releasing factor (HRF) was studied in four groups. These groups consisted of 32 newly diagnosed children with asthma, 40 good responders and 18 poor responders to IT (older than 2 years), and 15 healthy subjects. The results demonstrated (1) peripheral blood mononuclear cells of new patients produced a much greater HRF activity, either spontaneously or after stimulation, than did those of normal subjects, (2) the spontaneous HRF activity decreased significantly in good responders, whereas that of poor responders increased, (3) both the allergen (mite)- and mitogen (phytohemagglutinin [PHA])-stimulated HRF activity was decreased, although decrease was not significant, in good responders, but the activity was not changed in poor responders, (4) the granulocytes of new patients responded to HRF much more vigorously than did granulocytes of normal subjects. The responsiveness diminished significantly in both good and poor responders, although the magnitude of decrease was slightly greater in the former, (5) there was a positive correlation between PHA- and mite-stimulated HRF activity, mite-stimulated HRF activity and responsiveness to HRF, and plasma histamine level and responsiveness to HRF in the new patients, and (6) there was an inverse correlation between PHA-stimulated HRF production and responsiveness to HRF in good responders, but the correlation was positive in poor responders. Thus, IT is able to suppress the HRF activity, particularly the type of spontaneous synthesis, and responsiveness to HRF in clinically benefitted children with asthma, and this effect may be used to explain, partly, the efficacy of IT in a proportion of allergic patients.

Parkinson's disease (PD) is manifested by motor impairment, which may impede the ability to accurately perform motor tasks during functional magnetic resonance imaging (fMRI). Both temporal and amplitude deviations of movement performance affect the blood oxygenation level-dependent (BOLD) response. We present a general approach for assessing PD patients' movement control employing simultaneously recorded fMRI time series and behavioral data of the patients' kinematics using MR-compatible gloves. Twelve male patients with advanced PD were examined with fMRI at 1.5T during epoch-based visually paced finger tapping. MR-compatible gloves were utilized online to quantify motor outcome in two conditions with or without dopaminergic medication. Modeling of individual-level brain activity included (i) a predictor consisting of a condition-specific, constant-amplitude boxcar function convolved with the canonical hemodynamic response function (HRF) as commonly used in fMRI statistics (standard model), or (ii) a custom-made predictor computed from glove time series convolved with the HRF (kinematic model). Factorial statistics yielded a parametric map for each modeling technique, showing the medication effect on the group level. Patients showed bilateral response to levodopa in putamen and globus pallidus during the motor experiment. Interestingly, kinematic modeling produced significantly higher activation in terms of both the extent and amplitude of activity. Our results appear to account for movement performance in fMRI motor experiments with PD and increase sensitivity in detecting brain response to levodopa. We strongly advocate quantitatively controlling for motor performance to reach more reliable and robust analyses in fMRI with PD patients.

Symbiotic dinoflagellates (zooxanthellae) typically respond to extracts of host tissue with enhanced release of short-term photosynthetic products. We examined this "host release factor" (HRF) response using freshly isolated zooxanthellae of differing nutritional status. The nutritional status was manipulated by either feeding or starving the sea anemone Aiptasia pallida (Verrill). The release of fixed carbon from isolated zooxanthellae was measured using 14C in 30 min experiments. Zooxanthellae in filtered seawater alone released approximately 5% of photosynthate irrespective of host feeding history. When we used a 10-kDa ultrafiltrate of A. pallida host tissue as a source of HRF, approximately 14% of photosynthate was released to the medium. This increased to over 25% for zooxanthellae from anemones starved for 29 days or more. The cell-specific photosynthetic rate declined with starvation in these filtrate experiments, but the decline was offset by the increased percentage release. Indeed, the total amount of released photosynthate remained unchanged, or even increased, as zooxanthellae became more nutrient deficient. Similar trends were also observed when zooxanthellae from A. pallida were incubated in a 3-kDa ultrafiltrate of the coral Montastraea annularis, suggesting that HRF in the different filtrates operated in a similar manner. Our results support the suggestion that HRF diverts surplus carbon away from storage compounds to translocated compounds such as glycerol.