The behavioural state in human perinatal life

Behavioural states are easy to recognise in healthy neonates with a gestational age of 36 weeks or more. In younger neonates stable behavioural states, as seen at full-term, are not present, but activity cycles exist. In utero stable behavioural states can also be recognised from 36 to 38 weeks onwards. The existence of awake states in utero remains controversial. A close relationship exists between neural mechanisms regulating the behavioural state cycling and those modulating breathing. Our understanding of these is still very limited. The absence of behavioural states or of activity cycles is a very sensitive but non-specific sign of nervous system dysfunction in human perinatal life.     

Serum evaluation of the balance between soluble interleukin-2 and interleukin-4 receptors

To elucidate the usefulness of the simultaneous analysis of the multiple kinds of soluble cytokine receptors, we determined both the soluble interleukin 2 receptor (sIL-2R, Th1-type cytokine receptor) and the soluble interleukin 4 receptor (sIL-4R, Th2-type cytokine receptor) levels in the sera of healthy subjects as reference values and preliminarily applied to evaluate the patients with diarrhea positive (D+) hemolytic uremic syndrome (HUS) as the diagnostic parameter of the severity. Both sIL-2R and sIL-4R levels in the sera of healthy children were significantly higher than those of healthy adults (p<0.01). The serum sIL-2R level of the patients with severe HUS (n=4) was higher than that of the patients with mild/moderate HUS (n=6) at the initial stage (p<0.01) or healthy children (n=51, p<0.01). Whereas, the serum sIL-4R level of both the severe and mild/moderate groups was lower than that of the healthy control children, although there was no significant difference among the three groups. Namely, the soluble receptor balance (sIL-2R/sIL-4R) in the patients with severe HUS may shift. We considered that the evaluation of the balance between soluble cytokine receptors might be informative for the evaluation of the immune states, as well as the conventional cytokine balance (Th1/Th2).     

Analysis of EEG characteristic at early stages of depression using method of independent components

Independent Component Analysis (ICA) was used for 19-channel resting EEG analysis 111 patients at early stages of depressive disorder and 526 age-matched healthy subjects. Comparison of independent components power spectra in depressed patients and healthy subjects in two states: Eyes closed and Eyes open, has revealed significant differences between groups for three frequency bands: Theta (4-7.5 Hz), Alpha (7.5-14 Hz), and Beta (14-20 Hz). Increased power of alpha and theta activity in depressed patients at parietal and occipital sites may be caused by decreased cortical activation of these regions. Diffuse enhancement of beta activity level can correlate with anxiety symptoms which take an important place in clinical picture of depressive disorder at early stages. Using of ICA method for comparison of spectral characteristics of EEG in groups of patients with different brain pathology and healthy subjects gives a possibility to localize more precisely the discovered differences as compare to traditional analysis of EEG spectra.     

Shift in the balance between circulating thrombospondin-1 and vascular endothelial growth factor in cancer patients: relationship to platelet alpha-granule content and primary activation

Tumoral angiogenesis is regulated by the balance between factors that activate and inhibit angiogenesis. Elevated levels of activators have been associated with a poor prognosis in cancer patients, but little is known about the net balance between circulating activators and inhibitors in these patients. This study was designed to determine whether the balance between circulating concentrations of the angiogenesis inhibitor TSP-1 and the activator VEGF differs from that in healthy persons, and to shed light on the possible role of platelets in this balance. Twenty-five cancer patients and 18 healthy subjects were included. Serum and plasma concentrations of VEGF, TSP-1 and PF4 were measured by ELISA. Our results showed that in healthy subjects the balance between the TSP-1 and VEGF concentrations in serum and in serum minus plasma was twice to three times as high as in cancer patients (p < 0.05). The theoretical TSP-1 content per platelet was greater in healthy subjects than in patients (94 vs. 53.6 ng/mL, p < 0.05), and platelet activation (determined indirectly as the plasma concentration of PF4) was greater in cancer patients (129 vs. 48 IU/mL, p < 0.01). Platelet activation correlated significantly with serum concentration of TSP-1 (r = 0.470, p = 0.018) and showed a tendency toward correlation with plasma concentration of TSP-1 (r = 0.382, p = 0.059). Our findings show that the circulating TSP-1/VEGF balance is diminished in cancer patients. Platelet activation may play an important role in this decrease and may ultimately lead to increased angiogenic activity in these patients.     

Salivary Nickel and Chromium Levels in Orthodontic Patients with and Without Periodontitis: a Preliminary Historical Cohort Study

Many periodontal patients may need orthodontic treatment. Alterations in oral environment particularly the reduction of pH in periodontal patients could affect metal ion release from orthodontic appliances. However, there is no study on metal ion release in periodontal patients. The aim of this preliminary study was to comparatively evaluate, for the first time, salivary levels of nickel and chromium in periodontal patients (versus healthy controls) under orthodontic treatment for 2 months. In this in vivo study, 40 subjects were evaluated. Patient selection and standardization of orthodontic treatment protocols were prospectively designed and performed. Two groups of n = 20 each (control: healthy orthodontic patients, cohort: orthodontic patients with periodontitis) underwent similar protocols of fixed orthodontic treatment for 2 months. After 2 months, salivary nickel and chromium concentrations of the case and cohort groups were measured using inductively coupled plasma mass spectrometry (ICP-MS). The values were compared between the two groups using t test. There were 10 men and 10 women in each group. The mean age of patients was 34.6 ± 3.6 years old. The salivary level of nickel was 338.2 ± 235.5 ng/ml and 182.8 ± 116.5 ng/ml in the cohort and control groups, respectively (P = 0.0118). The salivary level of chromium was 7.4 ± 3.15 ng/ml in the cohort and 6.35 ± 2.39 ng/ml in the control group (P = 0.2214). Salivary level of nickel might be considerably higher in periodontal patients undergoing 2 months of orthodontic treatment compared to orthodontic patients with healthy gingivae.

     

Spectroscopic and functional characterization of T state hemoglobin conformations encapsulated in silica gels

Oxygen binding curves of sol-gel-encapsulated deoxy human adult hemoglobin (HbA) have previously revealed two distinct noncooperative populations with oxygen binding affinities approximately 1000 and 100 times lower than that of the high-affinity R state. The two populations which have been termed the low-affinity (LA) and high-affinity (HA) T states can be selectively stabilized using two different encapsulation protocols for deoxy-HbA. The present study seeks to understand the factors giving rise to these different affinity states. Visible and UV resonance Raman spectroscopies are used to characterize the conformational properties of both the deoxy and deoxy-turned-carbonmonoxy (CO) derivatives of HbA derived from the two encapsulation protocols. The geminate and bimolecular recombination of CO to the photodissociated CO derivatives is used to characterize the functional properties of the slowly evolving encapsulated populations. The results show that the initial deoxy-HbA populations are conformationally indistinguishable with respect to encapsulation protocol. The addition of CO to sol-gel-encapsulated deoxy-HbA triggers a detectable progression of conformational and functional changes. Visible resonance Raman spectra of the CO photoproduct reveal a progression of changes of the iron-proximal histidine stretching frequencies: 215, 222, 227, and 230 cm(-1). The low and high values correspond to the initial deoxy T state and liganded R (R(2)) state species, respectively. The 222 and 227 cm(-1) species are generated using encapsulation protocols that give rise to what are termed the LA and HA T states, respectively. The UV resonance Raman spectra of these and related species indicate that the progression from deoxy T to LA to HA is associated with a progressive loosening of T state constraints within the hinge and switch regions of the alpha(1)beta(2) interface. The time scale for the progression is determined by a balance between the ligation-initiated evolution toward high-affinity conformations and factors such as allosteric effectors, gel matrix, and added glycerol that slow ligand-binding-induced relaxation. Thus, it appears that the encapsulation protocol-dependent rate of ligand-binding-induced relaxation determines the functional properties of the initially encapsulated deoxy-HbA population.     

Socialization strategies and disease transmission in captive colonies of nonhuman primates

In captive research environments for nonhuman primates (NHP), social housing strategies are often in conflict with protocols designed to minimize disease transmission. This is particularly true in breeding colonies, and is especially relevant when attempting to eliminate specific pathogens from a population of primates. Numerous strategies have been used to establish such specific pathogen free (SPF) breeding colonies (primarily of macaques), ranging from nursery rearing of neonates to single housing of socially reared yearlings to the rearing of infants in large social groups. All these strategies attempt to balance the effects of the chosen socialization strategy on parameters related to disease transmission, including the ultimate elimination of the target pathogens. Such strategies may affect the overall disease states of NHP breeding colonies through selective breeding processes. This can occur either by creating subpopulations of animals that do not have target diseases (SPF colonies), but may have other issues; or by creating situations in which the "best" animals are sold and the breeding colony is stocked with animals that may be more disease susceptible than those that were sold. The disease states of NHP research colonies also may be affected by selective utilization programs, in which animals removed from the breeding colony for health/behavior reasons, are preferentially chosen for use in scientific investigations. Such utilization criteria raise the question of whether ideal subjects are being chosen for use in research. Finally, captive primate colonies, where both socialization and disease states are intensely managed, may provide opportunities for those testing predictions from models of the interactions of socialization and disease transmission in the evolution of wild populations of NHP. This would be especially true for some extreme conditions of these disease ecology models, given the exceedingly high social densities and levels of pathogen control that exist in many captive nonhuman primate colonies.     

Bridging the gap between temporomandibular disorders,static balance impairment and cervicogenic dizziness: Posturographic and clinical outcomes

Several studies have investigated the possible influence of temporomandibular disorders (TMD) on body posture and whether cervical spine disorders, such as cervicogenic dizziness (CGD) could play an additional role in affecting static balance. The purpose of this study was to analyze static postural behavior by means of static posturography, in patients affected by either TMD or CGD alone or by both conditions, and to compare findings with a group of healthy subjects. Significant changes in posturographic parameters were found among the three groups of patients and when compared with controls. When the three study groups were compared to each other, subjects affected by a combination of TMD and CGD showed worse postural performances with respect to subjects affected by CGD or TMD alone. Correlations with self-perceived dizziness, anxiety, depression and jaw functionality, investigated by means of validated questionnaires, were found among all patient groups. These results provide new evidences for the presence of static balance alterations in patients suffering from TMD with and without associated cervical spine impairment, by using a reliable diagnostic technique. Further studies are needed in order to identify any causal relation between these two disorders.     

Electroencephalograms of patients with initial signs of depression: Independent component analysis

Independent component analysis (ICA) of 19-channel background EEG was performed in 111 patients with the early signs of depressive disorders and in 526 healthy subjects. The power spectra of the independent components were compared in the depressive patients and in healthy subjects at the eyes closed and eyes opened states. Statistically significant differences between the groups were detected in three frequency bands: θ (4–7.5 Hz), α (7.5–14 Hz), and β (14–20 Hz). Increased θ and α activities in parietal and occipital derivations of depressive patients may have been caused by a reduced cortical activity in the projection of these derivation. Diffuse enhancement of the β activity may be correlated with anxiety symptoms that are pronounced in the clinical picture of depressive disorders at early stages of the disease. ICA used to compare quantitative EEG parameters in different groups of patients and in healthy persons makes it possible to localize the differences more accurately than the traditional analysis of EEG spectra.     

Proteomic profiling of hepatitis B virus-related hepatocellular carcinoma with magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Proteomic techniques are promising strategies in the surveillance of hepatocellular carcinoma (HCC). This study aimed to investigate the serum profiling with magnetic bead (MB) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and to further identify the biomarkers for HCC. Serum samples from 80 chronic hepatitis B (CHB) patients, 94 HCC concomitant with HBV patients and 24 healthy subjects were examined by MALDI-TOF MS after peptide enrichment on MBs. Based on the genetic algorithm, diagnostic models for HCC were established between 30 HCC patients and 24 healthy subjects/30 CHB patients. Validations were done with the remaining cases. Markers in the models were identified through liquid chromatography (LC)/MS-MS. The three groups were well separated from each other and two discrimination models were established for HCC. The overall recognition capability of these two models was 96.25% and 93.33%, respectively. Validations showed the misdiagnosis ratio for HCC was 1.6% and 23.4%, respectively. The identified biomarkers for HCC included prothrombin precursor (fragment), calcium-dependent secretion activator 1, Baculoviral inhibitor of apoptosis repeat-containing protein 6, etc. MB-based MALDI-TOF MS is applicable in identifying the serum biomarkers and can be used in the surveillance of HCC among HBV-infected patients.     

Comparison of different neuron models to conductance-based post-stimulus time histograms obtained in cortical pyramidal cells using dynamic-clamp in vitro

A wide diversity of models have been proposed to account for the spiking response of central neurons, from the integrate-and-fire (IF) model and its quadratic and exponential variants, to multiple-variable models such as the Izhikevich (IZ) model and the well-known Hodgkin–Huxley (HH) type models. Such models can capture different aspects of the spiking response of neurons, but there is few objective comparison of their performance. In this article, we provide such a comparison in the context of well-defined stimulation protocols, including, for each cell, DC stimulation, and a series of excitatory conductance injections, arising in the presence of synaptic background activity. We use the dynamic-clamp technique to characterize the response of regular-spiking neurons from guinea-pig visual cortex by computing families of post-stimulus time histograms (PSTH), for different stimulus intensities, and for two different background activities (low- and high-conductance states). The data obtained are then used to fit different classes of models such as the IF, IZ, or HH types, which are constrained by the whole data set. This analysis shows that HH models are generally more accurate to fit the series of experimental PSTH, but their performance is almost equaled by much simpler models, such as the exponential or pulse-based IF models. Similar conclusions were also reached by performing partial fitting of the data, and examining the ability of different models to predict responses that were not used for the fitting. Although such results must be qualified by using more sophisticated stimulation protocols, they suggest that nonlinear IF models can capture surprisingly well the response of cortical regular-spiking neurons and appear as useful candidates for network simulations with conductance-based synaptic interactions.     

Solid-state NMR characterization of conformational plasticity within the transmembrane domain of the influenza A M2 proton channel

Membrane protein function within the membrane interstices is achieved by mechanisms that are not typically available to water-soluble proteins. The whole balance of molecular interactions that stabilize three-dimensional structure in the membrane environment is different from that in an aqueous environment. As a result interhelical interactions are often dominated by non-specific van der Waals interactions permitting dynamics and conformational heterogeneity in these interfaces. Here, solid-state NMR data of the transmembrane domain of the M2 protein from influenza A virus are used to exemplify such conformational plasticity in a tetrameric helical bundle. Such data lead to very high resolution structural restraints that can identify both subtle and substantial structural differences associated with various states of the protein. Spectra from samples using two different preparation protocols, samples prepared in the presence and absence of amantadine, and spectra as a function of pH are used to illustrate conformational plasticity.     

Solid-state NMR characterization of conformational plasticity within the transmembrane domain of the influenza A M2 proton channel

Membrane protein function within the membrane interstices is achieved by mechanisms that are not typically available to water-soluble proteins. The whole balance of molecular interactions that stabilize three-dimensional structure in the membrane environment is different from that in an aqueous environment. As a result interhelical interactions are often dominated by non-specific van der Waals interactions permitting dynamics and conformational heterogeneity in these interfaces. Here, solid-state NMR data of the transmembrane domain of the M2 protein from influenza A virus are used to exemplify such conformational plasticity in a tetrameric helical bundle. Such data lead to very high resolution structural restraints that can identify both subtle and substantial structural differences associated with various states of the protein. Spectra from samples using two different preparation protocols, samples prepared in the presence and absence of amantadine, and spectra as a function of pH are used to illustrate conformational plasticity.     

Urinary thromboxane A2/prostacyclin balance reflects the pathological state of a diabetic

Levels of the stable urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 2,3-dinor-6-keto-prostaglandin F1alpha (2,3-dinor-6-keto-PGF1alpha) were measured in diabetics to elucidate the relation between the thromboxane A2/prostacyclin (TX/PGI) balance and pathological states of diabetes mellitus. 11-Dehydro-TXB2 and 2,3-dinor-6-keto-PGF1alpha were derivatized to methyl ester-propylamide-dimethylisopropylsilyl ether and methyl ester-methoxime-dimethylisopropylsilyl ether derivatives, respectively, and applied to a gas chromatography/selected ion monitoring. The TX/PGI ratios of diabetics were higher than those of healthy volunteers, suggesting the hypercoagulative states of this disease. The ratios showed positive correlations with the levels of blood glucose. The levels of hemoglobin A1c and triglyceride were correlated weakly with the ratio. Some of the patients who had relatively low levels of blood glucose also showed high TX/PGI ratios. Furthermore, the ratio increased in the order of the groups 1, 2, and 3; group 1 contained patients who did not take medicine for diabetes, group 2 contained those who took oral hypoglycemic agents, and group 3 contained those who received insulin therapy. These observations indicate that the TX/PGI ratio reflects the pathological conditions of diabetes and is a useful marker, having few different features from other markers that are presently used.     

Elevated Levels of Procoagulant Plasma Microvesicles in Dialysis Patients

Cardiovascular (CV) death remains the largest cause of mortality in dialysis patients, unexplained by traditional risk factors. Endothelial microvesicles (EMVs) are elevated in patients with traditional CV risk factors and acute coronary syndromes while platelet MVs (PMVs) are associated with atherosclerotic disease states. This study compared relative concentrations of circulating MVs from endothelial cells and platelets in two groups of dialysis patients and matched controls and investigated their relative thromboembolic risk. MVs were isolated from the blood of 20 haemodialysis (HD), 17 peritoneal dialysis (PD) patients and 20 matched controls. Relative concentrations of EMVs (CD144^{+ ve}) and PMVs (CD42b^{+ ve}) were measured by Western blotting and total MV concentrations were measured using nanoparticle-tracking analysis. The ability to support thrombin generation was measured by reconstituting the MVs in normal plasma, using the Continuous Automated Thrombogram assay triggered with 1µM tissue factor. The total concentration of MVs as well as the measured sub-types was higher in both patient groups compared to controls (p<0.05). MVs from HD and PD patients were able to generate more thrombin than the controls, with higher peak thrombin, and endogenous thrombin potential levels (p<0.02). However there were no differences in either the relative quantity or activity of MVs between the two patient groups (p>0.3). Dialysis patients have higher levels of circulating procoagulant MVs than healthy controls. This may represent a novel and potentially modifiable mediator or predictor of occlusive cardiovascular events in these patients.     

A Correlational Study of Scoliosis and Trunk Balance in Adult Patients with Mandibular Deviation

Previous studies have confirmed that patients with mandibular deviation often have abnormal morphology of their cervical vertebrae. However, the relationship between mandibular deviation, scoliosis, and trunk balance has not been studied. Currently, mandibular deviation is usually treated as a single pathology, which leads to poor clinical efficiency. We investigated the relationship of spine coronal morphology and trunk balance in adult patients with mandibular deviation, and compared the finding to those in healthy volunteers. 35 adult patients with skeletal mandibular deviation and 10 healthy volunteers underwent anterior X-ray films of the head and posteroanterior X-ray films of the spine. Landmarks and lines were drawn and measured on these films. The axis distance method was used to measure the degree of scoliosis and the balance angle method was used to measure trunk balance. The relationship of mandibular deviation, spine coronal morphology and trunk balance was evaluated with the Pearson correlation method. The spine coronal morphology of patients with mandibular deviation demonstrated an “S” type curve, while a straight line parallel with the gravity line was found in the control group (significant difference, p<0.01). The trunk balance of patients with mandibular deviation was disturbed (imbalance angle >1°), while the control group had a normal trunk balance (imbalance angle <1°). There was a significant difference between the two groups (p<0.01). The degree of scoliosis and shoulder imbalance correlated with the degree of mandibular deviation, and presented a linear trend. The direction of mandibular deviation was the same as that of the lateral bending of thoracolumbar vertebrae, which was opposite to the direction of lateral bending of cervical vertebrae. Our study shows the degree of mandibular deviation has a high correlation with the degree of scoliosis and trunk imbalance, all the three deformities should be clinically evaluated in the management of mandibular deviation.     

Empowering GPs as purchasers.

FHSAs have defined their role in purchasing primary care FHSAs have also found themselves intermediaries between district health authorities and general practitioners All of the purchasing authorities recognise the need to educate general practitioners on how to use their influence in the purchasing process General practitioners should be involved in the purchasing process as they purchase the bulk of health care; are the first point of contact for the users of the health service; need to have input on what is purchased; and need to be able to manage the changes resulting from the shift in the balance of power towards primary care The involvement of general practitioners in the purchasing process at present varies considerably among health authorities. Several district health authorities have developed models of purchasing that enable different levels of involvement     

What Does Brain Response to Neutral Faces Tell Us about Major Depression? Evidence from Machine Learning and fMRI

Introduction

A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients.

Methods

Two independent depressed samples: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier’s predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients.

Results

Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls.

Conclusions

Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in brain activation might underlie the behavioural misinterpretation of the neutral faces content by the depressed patients.     

Differential effects of 2'-deoxyguanosine on peripheral blood mononuclear cell proliferation in healthy donors and Hashimoto's thyroiditis patients

Abstract. The aim of this study was to determine possible differences in peripheral blood mononuclear cells (PBMC) proliferation of healthy donors and Hashimoto's thyroiditis patients and whether a statistical approach to cell proliferation analysis might be used to discern the differences. The effect of a wide range of 2'-deoxyguanosine (dGuo) concentrations (0–1250 μM) on the mitogen-induced proliferation of PBMC was studied in healthy donors and Hasimoto's thyroiditis patients. Activity levels of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) in PBMC were also measured. For the first time in a study of these models of dGuo toxicity in vitro , the analysis of polynomial trends of orders from 1 to 7 was applied to evaluate cell proliferation. A dose-dependent inhibition of mitogen-induced PBMC proliferation was observed in both groups. Data for linear trend established that PBMC from Hashimoto's thyroiditis patients were more sensitive to dGuo toxicity than PBMC from healthy donors. A positive quadratic trend at low dGuo doses was found in the cell proliferation of Hashimoto's thyroiditis patients. A decrease in PNP activity ( P < 0.025) and an increase in ADA activity ( P < 0.005) was observed in PBMC of Hashimoto's thyroiditis group. The differences in PBMC proliferation subjected to dGuo toxicity between the two groups could be related with the distinct pattern of purine salvage enzymes observed.