The importance of instrumental assessment in disorders of consciousness: a comparison between American, European, and UK International recommendations.

The use of instrumental tools for improving both the diagnostic accuracy and the prognostic soundness in patients with disorders of consciousness (DOC) plays an important role. However, the most recent international guidelines on DOC published by the American and the European Academies of Neurology and by the UK Royal College of Physicians contain heterogeneous recommendations on the implementation of these techniques in the clinical routine for both diagnosis and prognosis. With the present work, starting from the comparison of the DOC guidelines' recommendations, we look for possible explanations behind such discrepancies considering the adopted methodologies and the reference health systems that could have affected the guidelines' perspectives. We made a provocative argument about the need to find the most appropriate common methodology to retrieve and grade the evidence, increase the meta-analytic studies, and reduce the health policies that influence on the guidelines development that, in turn, should inform the health policies with the strongest scientific evidence.

Rubber Hand Illusion survives Ventral Premotor area inhibition: A rTMS study.

The sense of body ownership is a fundamental feature that refers to the ability to recognize our body as our own, allowing us to interact properly with the outside world. Usually, it is explored by means of the Rubber Hand Illusion (RHI) during which a dummy hand is incorporated in the mental representation of one's own body throughout a multisensory (visuo-tactile) integration mechanism. Particular attention has been paid to the neurofunctional counterparts of this mechanism highlighting the pivotal role of an occipito-parieto-frontal network involving the Ventral Premotor area (PMv). To date, the specific role of the PMv in generating the sense of ownership is still unknown. In this study, we aimed at exploring the role of PMv in generating and experiencing the RHI. Off-line repetitive Transcranial Magnetic Stimulation (rTMS) was applied to a group of 24 healthy participants whilst changes in proprioceptive judgment and self-reported illusion sensations were collected and analysed separately. The PMv was not directly implicated in generating the sense of ownership. Indeed, its inhibition affected the explicit detection of the visuo-tactile congruence without interfering with the illusion experience itself. We hypothesized that the conscious visuo-tactile congruence detection may be independent from the conscious illusion experience. Also, our results support the view that the RHI grounds on a complex interaction between bottom-up and top-down processes, as the visuo-tactile integration per se may be not sufficient to trigger the subjective illusion.

Structure, function and control of complement C5 and its proteolytic fragments.

As part of the innate immune system, the complement system recognises a wide range of non-self structures present on pathogens or altered self cells. Its activation elicits proteolytic cascades which eventually results in the cleavage of the C5 protein into two fragments, C5a and C5b. The small anaphylatoxin C5a induces a variety of biological responses upon binding to the 7TM receptors C5aR and the C5L2, while the large C5b fragment nucleates formation of the membrane attack complex capable of killing susceptible pathogens by the formation of a pore structure in association with complement components C6, C7, C8, and C9. A number of regulatory molecules help to control C5 mediated immune responses towards host cells, but in several major inflammatory conditions including sepsis and arthritis, C5a is believed to contribute significantly to disease etiology. Inhibition of membrane attack complex assembly is already approved for treatment of paroxysmal nocturnal haemoglobinuria and atypical hemolytic uremic syndrome. A number of recent crystal structures have provided a comprehensive insight into the architecture and properties of intact C5 and its fragments, and how pathogens interfere with their function. Here we review the functional and structural aspects of C5 and its fragments, the pathological conditions associated with them, and strategies employed by pathogens to interfere with the biological function of C5. Structural insight and elucidation of evasion strategies employed by pathogens present a unique opportunity for promoting the development of novel selective C5 inhibitors with therapeutic applications.

Effectiveness of the photochemical reflectance index to track photosynthetic activity over a range of forest tree species and plant water statuses.

In this study, we investigated the potential of the photochemical resistance index (PRI) to track photosynthetic activity under water stress conditions by measuring PRI, leaf fluorescence, the xanthophyll cycle and photosynthetic activity in different forest tree species subjected to progressive drought. The PRI declined with pre-dawn water potential and a significant relationship between PRI and the xanthophyll de-epoxidation state (DEPS) was observed, although with large interspecific variability in the sensitivity of PRI to changes in DEPS. For single tree species, a strong relationship was observed on either PRI light saturated photosynthesis or PRI maximum photochemical efficiency of PSII (ΔF/Fm'); a larger variability in both relationships was apparent when data from different species were pooled together. However, an improved correlation was shown only in the former relationship by plotting the ΔPRI (dawn PRI minus the midday PRI values). Thus, we conclude that PRI is able to provide a good estimate of maximum CO2 assimilation at saturating light and ΔF/Fm' for single tree species, despite the severe drought conditions applied. PRI should be applied more cautiously when dealing with multispecific forests because of confounding factors such as the strong interspecific differences in the initial value of PRI and in the sensitivity of PRI to changes in DEPS in response to drought.

Maternal body composition at term gestation and birth weight: is there a link?

To assess the relative influence of maternal body composition at late gestation on birth weight, we examined maternal body composition near term (36.50+/-2.67 weeks gestation) in a group of 29 women, aged 20-39 years. The women came to the laboratory after an overnight fast. After anthropometric measurements, bioelectrical impedance analysis (BIA) was performed, determining resistance (R) and reactance (Xc), with a Tefal scale at 50 kHz. Fat mass (FM, kg) and fat-free mass (FFM, kg) were determined with the total body water (TBW) equation of Siri. The correlation between BIA parameters and birth weights was examined by linear regression analysis. All subjects delivered between 37 and 41 weeks' gestation. The mean+/-SD values of the studied parameters were: Xc=490.00+/-77.34 ohm, R=55.71+/-8.71 ohm, FM=24.18+/-6.51 kg, FFM=45.82+/-2.65 kg, maternal weight gain=9.51+/-6.43 kg, birth weight=3.43+/-0.36 kg. A direct significant correlation was found between FFM, maternal weight gain, and birth weight. It is known that in late pregnancy, maternal weight gain over gestation is linked to birth weight. We observed that FFM was the most important maternal body component associated with the newborn weight at term gestation, and we believe that this finding might be elucidated by fluid retention. In fact, resistance seemed to be inversely related to birth weight and we do not overlook the link between resistance and TBW. The implementation of our study could shed more light on the influence of maternal body composition on birth weight.

Postpartum thyroiditis is associated with fluctuations in transforming growth factor-beta1 serum levels.

Postpartum thyroiditis (PPT) is characterized by a rapid evolution and recovery of euthyroidism. Therefore, it can represent a good model to study early cytokine fluctuations in autoimmune thyroid diseases. TGFbeta1 is an immunosuppressive cytokine, as it inhibits T and B cell proliferation, natural killer cell cytotoxic activity, and the generation of T cell cytotoxicity. The aim of this study was to assess serum concentrations of TGFbeta1 during pregnancy and to study possible serum fluctuations of this cytokine during the different phases of PPT. Thyroid biochemical pattern, antithyroid autoantibodies (ATA), and total and active TGFbeta1 (aTGFbeta1) serum concentrations were evaluated in 63 pregnant women. Thirty-four of them were ATA(+), and 29 were ATA(-). Twenty of the 34 ATA(+) women were followed in the postpartum year. Nine of these 20 women developed PPT; 11 remained euthyroid. All of the PPT women became euthyroid during the follow-up. Our results showed 1) detectable serum levels of aTGFbeta1 in 50% of ATA(+) pregnant women, suggesting that the presence of autoantibodies may characterize a favorable condition for TGFbeta1 activation; and 2) decreased total TGFbeta1 and increased aTGFbeta1 serum levels during the active phase of PPT in ATA(+) women. This seems to suggest that inflammation may be responsible for TGFbeta1 activation and autoantibody increase because of antigen release. Although further studies of women with persistent hypothyroidism after the postpartum year are needed, the possibility that the enhanced activation of TGFbeta1 may contribute to resolution of thyroid inflammation postpartum cannot be excluded.

The relationship between tree height and leaf area: sapwood area ratio.

The leaf area to sapwood area ratio (A l:A s) of trees has been hypothesized to decrease as trees become older and taller. Theory suggests that A l:A s must decrease to maintain leaf-specific hydraulic sufficiency as path length, gravity, and tortuosity constrain whole-plant hydraulic conductance. We tested the hypothesis that A l:A s declines with tree height. Whole-tree A l:A s was measured on 15 individuals of Douglas-fir (Pseudotsuga menziesii var. menziesii) ranging in height from 13 to 62 m (aged 20-450 years). A l:A s declined substantially as height increased (P=0.02). Our test of the hypothesis that A l:A s declines with tree height was extended using a combination of original and published data on nine species across a range of maximum heights and climates. Meta-analysis of 13 whole-tree studies revealed a consistent and significant reduction in A l:A s with increasing height (P<0.05). However, two species (Picea abies and Abies balsamea) exhibited an increase in A l:A s with height, although the reason for this is not clear. The slope of the relationship between A l:A s and tree height (ΔA l:A s/Δh) was unrelated to mean annual precipitation. Maximum potential height was positively correlated with ΔA l:A s/Δh. The decrease in A l:A s with increasing tree size that we observed in the majority of species may be a homeostatic mechanism that partially compensates for decreased hydraulic conductance as trees grow in height.

Regulation of the serotonin transporter by interacting proteins.

The serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by serotonin [5-hydroxytryptamine (5-HT)]. Recent evidence suggests that SERT and other neurotransmitter transporters are tightly regulated. Activation of protein kinase C results in a decrease in SERT-mediated 5-HT uptake, which is due to an internalization of the transporter. However, to date little is known about the mechanism and proteins involved in the down-regulation of the transporter. One candidate SERT-regulatory protein is the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) protein, syntaxin 1A (Syn1A), which has recently been implicated in the regulation of ion channels as well as the SERT-related gamma-aminobutyric acid- and glycine-transporters. Using 5-HT uptake assays, confocal microscopy and glutathione S-transferase (GST) pull-down assays we showed that Syn1A also interacts with SERT and alters the subcellular localization of the transporter, resulting in a reduction of 5-HT transport. In addition, we have used the yeast two-hybrid system to search for novel regulatory proteins that interact with the cytoplasmic N-terminal domain of SERT. By screening rat brain cDNA library we have identified six potential SERT-binding proteins. Here we also present progress towards the elucidation of the biological relevance of these proteins and their potential role for the regulation of the serotonin transporter.

High frequency of antithyroid autoantibodies in pregnant women at increased risk of gestational diabetes mellitus.

BACKGROUND: Thyroid autoantibodies (ThyAb) and subclinical hypothyroidism occur more frequently in pregnant women with insulin-dependent diabetes mellitus than in healthy pregnant women. Few studies have investigated the presence of ThyAb in women with gestational diabetes mellitus (GDM), and no significant association between diabetes in pregnancy and thyroid function has been reported. OBJECTIVE: To assess the thyroid biochemical profile and estimate the prevalence of ThyAb in a group of pregnant women at increased risk of GDM due to family and personal risk factors, and to investigate the relationship between a positive family history of diabetes or thyroid diseases and the eventual presence of ThyAb during pregnancy. METHODS: Oral glucose tolerance, serum ThyAb and thyroid function were evaluated in 181 pregnant women with increased risk for GDM (study group). Seventeen healthy pregnant women without risk factors for GDM and with a normal glucose tolerance were recruited as controls. RESULTS: The women who developed GDM showed a mean free thyroxine concentration significantly lower than that observed in the healthy pregnant women and in those with impaired gestational glucose tolerance and normal glucose tolerance. Twenty-nine of the 181 women in the study group (16%) were ThyAb positive. However, the risk of being ThyAb positive during pregnancy was three times greater in the women with positive family history of both diabetes mellitus and thyroid disease than in those with no family history of these conditions. CONCLUSIONS: This study showed that women with increased risk of GDM, mostly those with family history of diabetes mellitus and thyroid disease, also have an increased risk of being ThyAb positive during pregnancy. It also highlighted the importance of evaluating thyroid function in pregnant women with impaired glucose tolerance, in view of their increased risk of subclinical hypothyroidism.

Multifrequency bioelectrical impedance analysis in women with a normal and hypertensive pregnancy.

BACKGROUND: An increase in total body water is common in normal pregnancy. It is thought to be an important mechanism of maternal adaptation to pregnancy. OBJECTIVE: The aim of the present study was to assess longitudinal changes in body water compartments in pregnant women and to correlate these measurements with the course of pregnancy. DESIGN: One hundred seventy-three pregnant women with apparently normal, single pregnancies participated in this longitudinal study. Anthropometric measurements and multifrequency bioelectrical impedance were performed during the first, second, and third trimesters of pregnancy. RESULTS: One hundred three of the women completed all of the measurements; 50 of the women had a normal pregnancy and 13 had gestational hypertension. Total body water, extracellular water, and intracellular water values in normal pregnancies showed a significant, progressive increase throughout pregnancy. In women with gestational hypertension, total body water, extracellular water, and intracellular water values showed an opposite trend, suggesting a lack of plasma volume expansion through fluid-retention mechanisms. CONCLUSIONS: Our results show that multifrequency bioelectrical impedance analysis can be used to monitor variations in body water compartments in normal pregnancy and detect gestational hypertension.

Is neuronal nitric oxide involved in adjuvant-induced joint inflammation?

Several reports have described a role of macrophagic, endothelial and synoviocytal nitric oxide (NO) in inflammation, immunity and sensory processes in joint diseases. In view of the role of the peripheral nervous system in arthritis and owing to the presence of NO-producing neurons in primary sensory neurons, we have investigated the possible role of neuronal NO during adjuvant-induced joint inflammation in rats. Neural nitric oxide synthase production in sensory ganglia and the spinal cord was investigated by in situ hybridization and immunocytochemistry. Neuronal NO synthase mRNA expression and neuronal NO synthase immunoreactivity increased in lumbar dorsal root ganglia in arthritic rats compared to those of normal rats, whereas neuronal NO synthase mRNA expression decreased in lamina X and lamina I-II of the lumbar spinal cord. The administration of the selective neuronal NO synthase inhibitor 7-nitro indazole, reduced the joint inflammation, whereas the administration of the inducible NO synthase selective inhibitor, aminoguanidine, had no effect on inflammation when administered daily from the third day after adjuvant. These findings could indicate a role for neural NO in adjuvant arthritis.

The response of Pinus sylvestris to drought: stomatal control of transpiration and hydraulic conductance.

We investigated the impact of drought on the physiology of 41-year-old Scots pine (Pinus sylvestris L.) in central Scotland. Measurements were made of the seasonal course of transpiration, canopy stomatal conductance, needle water potential, xylem water content, soil-to-needle hydraulic resistance, and growth. Comparison was made between drought-treated plots and those receiving average precipitation. In response to drought, transpiration rate declined once volumetric water content (VWC) over the top 20 cm of soil reached a threshold value of 12%. Thereafter, transpiration was a near linear function of soil water content. As the soil water deficit developed, the hydraulic resistance between soil and needles increased by a factor of three as predawn needle water potential declined from -0.54 to -0.71 MPa. A small but significant increase in xylem embolism was detected in 1-year-old shoots. Stomatal control of transpiration prevented needle water potential from declining below -1.5 MPa. Basal area, and shoot and needle growth were significantly reduced in the drought treatment. In the year following the drought, canopy stomatal conductance and soil-to-needle hydraulic resistance recovered. Current-year needle extension recovered, but a significant reduction in basal area increment was evident one year after the drought. The results suggest that, in response to soil water deficit, mature Scots pine closes its stomata sufficiently to prevent the development of substantial xylem embolism. Reduced growth in the year after a severe soil water deficit is most likely to be the result of reduced assimilation in the year of the drought, rather than to any residual embolism carried over from one year to the next.

Thyroid autoimmunity in pregnant women at risk for GDM.

Presence of antithyroid autoantibodies (ThyAb) during pregnancy is strictly related to the risk of developing post partum thyroiditis (PPT) and this risk is increased in IDDM pregnant women. Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of variable severity that begins, or is first diagnosed, during pregnancy. GDM is considered a risk factor for both type 1 and type 2 diabetes and various non-organ specific autoantibodies have been found to be associated with GDM, although there is little information on the association of GDM with thyroid autoimmunity. In this study oral glucose tolerance and prevalence of ThyAb were evaluated in a group of 41 pregnant women at increased risk of developing GDM and in a healthy control group. Our results showed that 22% of GDM risk group had impaired glucose gestational tolerance (IGGT) or GDM at the time of oral glucose tolerance test (OGTT). Moreover, ThyAb prevalence found in the women at increased risk of GDM (14.6%) was similar to that observed in healthy pregnant controls (12.5%). Nevertheless ThyAb frequency was higher in those GDM risk women with family history of diabetes (30.7%).

Occupational genotoxicity assessment by mutagenicity assays.

Mutagenic activity measured by Ames test and by gene conversion, point mutation and mitochondrial mutability in Saccharomyces cerevisiae D7 strain was determined in the indoor environment of a glass factory. The results suggest that the increase in mutagenicity of air sample collected near the machinery is due to the thermal decomposition of oils. Modified assays were therefore compared for their ability to detect mutagens contained in urinary concentrates of exposed workers. The bacterial tests were performed by microsuspension assay in TA98, TA100 strains and in YG1024, YG1029 strains which overproduce O-acetyltransferase. Significant differences are evidenced both in the eukaryotic and prokaryotic systems.

[Nose disease caused by occupational exposure to chromium in the electroplating industry: cytomorphological aspects]. / Rinopatia da esoposizione professionale a cromo nell'industria galvanica: aspetti citomorfologici.

Twenty-six workers were studied (9 chrome-platers exposed to chromium dioxide and 17 workers exposed to metallic chromium dust) in order to investigate the macroscopic and cytological changes of the nasal mucosa due to exposure to water-soluble hexavalent chromium or to metallic chromium dust in the electroplating industry and the role of different valencies in the onset of nasal disease. Experimental and epidemiological data have shown that hexavalent chromium, which has strong oxidative power, induces more noticeable toxic effects on tissues and mucous membranes than other compounds. The correlation between the degree of local toxic effects and the chemical state of chromium was demonstrated in both the macro- and the microscopic investigations and in particular in the cytological examinations: cases of atypia were found only in workers exposed to hexavalent chromium. Evidence of atypia raises the question of whether hexavalent chromium may act as a carcinogenic agent on the rhinosinusal mucosa. For this reason, the introduction of cytological nasal examination in health surveillance programmes for this category of workers acquires considerable importance. Sample collection from the nasal mucosa by brushing is the method of choice since it is simple, non-invasive and gives good diagnostic results.

Phase II double-blind randomized study of lonidamine and radiotherapy in epidermoid carcinoma of the lung.

Patients with non metastatic squamous cell lung cancer were treated with radiotherapy (RT) plus lonidamine (LND) or placebo (PLAC), according to a randomized double-blind study design. Treatment with lonidamine 150 mg t.i.d. (27 patients) or placebo (23 patients) started 3 days before RT, lasted up to 7 months. Partial responses were observed in 14 and 6 patients respectively in the LND + RT and PLAC + RT groups. Statistical analysis of the survival curves showed no significant difference between the LND + RT (median 311 days) and PLAC + RT (median 193 days) groups. Stage III patients survived significantly longer (p less than 0.05) when treated with LND + RT (median 318 days) than with PLAC + RT (median 163 days). No synergistic toxic effects between radiation and LND were noted. To confirm these data a new and larger multicentric study is now in progress.