Simulating oil-driven abundance changes in benthic marine invertebrates using an ecosystem model.

Field studies showed that benthic macrofauna and meiofauna abundances increased with sediment oil concentration in areas affected by the Deepwater Horizon (DWH) oil spill. Benthic invertebrate biomass shows a dome-shaped relationship with respect to petrogenic hydrocarbon concentrations suggesting a positive effect on biomass at low-to-medium oil concentrations and a negative effect at high concentrations. If this is due to enrichment of the benthic food web, then this adds to an emerging picture of a food web response over a large spatial area with both abundance increases and decreases as a result of DWH. We would be obliged to consider long term multispecies effects beyond the initial pulse disturbance in modeling impacts and recovery of economically valuable species. An Atlantis ecosystem model of the Gulf of Mexico is used to simulate three mechanisms that could explain observed changes in the invertebrate community. Scenario 1 is that stimulation of surface primary productivity occurred as a result of nutrient loading caused by diversion of Mississippi River water into Barataria Bay (a mitigation action taken during the DWH oil spill). Scenario 2 is that enrichment of the benthos occurred due to detrital loading from marine oil snow sedimentation and flocculent accumulation (MOSSFA). Scenario 3 is that predator declines and/or avoidance of oiled areas caused a release of predation mortality on benthic invertebrates. Scenario 2 (MOSSFA) stimulated the detritus-driven food web and was best able to cause a net increase in invertebrate biomass despite a realistic amount of oil toxicity. Scenario 3 (predator release) plausibly could have contributed to changes in benthic invertebrates. Scenario 1 (nutrient loading) had little impact on the benthos suggesting the benthic food web is decoupled from local pelagic production sources.

Drawing the borders of the mesophotic zone of the Mediterranean Sea using satellite data.

The 30-150 m bathymetric range is commonly adopted in the literature to constrain the mesophotic zone. However, such depth interval varies depending on sunlight penetration, which is primarily a function of solar radiation incidence and water clarity. This is especially obvious in the Mediterranean Sea with its peculiar biophysical properties. Integrating information on light regime in the estimation of the bathymetric range of the mesophotic zone would provide a more robust definition, orienting conservation actions targeting its ecosystems. We present a first assessment of the spatial and vertical extension of the mesophotic zone in the Mediterranean Sea based upon light penetration, comparing our prediction with literature data. Our study also represents a baseline to monitor future variations in the bathymetric interval associated with the mesophotic zone in the Mediterranean Sea in relation to global changes.

Seismic Hazards Implications of Uplifted Pleistocene Coral Terraces in the Gulf of Aqaba.

The Gulf of Aqaba transform plate boundary is a source of destructive teleseismic earthquakes. Seismicity is concentrated in the central sub-basin and decreases to both the north and south. Although principally a strike-slip plate boundary, the faulted margins of the Gulf display largely dip-slip extensional movement and accompanying footwall uplift. We have constrained rates of this uplift by measurements of elevated Pleistocene coral terraces. In particular the terrace that formed during the last interglacial (~125 ka) is found discontinuously along the length of the Gulf at elevations of 3 to 26 m. Global sea level was ~7 m higher than today at 125 ka indicating net maximum tectonic uplift of ~19 m with an average rate of ~0.015 cm/yr. Uplift has been greatest adjacent to the central sub-basin and like the seismicity decreases to the north and south. We suggest that the present pattern of a seismically active central region linked to more aseismic areas in the north and south has therefore persisted for at least the past 125 kyr. Consequently the potential for future destructive earthquakes in the central Gulf is greater than in the sub-basins to the north and south.

A method for counting monosodium urate crystals in synovial fluid.

This study was aimed to standardize the technique for counting monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with gout. A total of 52 SF specimens were examined under a polarized light microscope. The amount of SF ranged between 0.1 and 45 mL (median 3 mL). MSU crystals were counted in four areas with the same size at 400x magnification. Cytological examination of the same specimens was also performed. Median leukocyte count was 400 cells/mm3 (range 50-14,000 cells/mm3), with a median percentage of polymorphonuclear leukocytes of 9% (range 0%-98%). Median crystal count was 179.5 (range 3-1600). Inter- reader and intra-reader agreement in crystal counting were good with a weighed k of 0.89 [95% confidence interval (CI) 0.85-0.94] and 0.89 (95% CI 0.84-0.93), respectively. Our data indicate that the SF MSU crystal count is a feasible and highly reliable technique.

Endothelin receptor antagonists: effects on extracellular matrix synthesis in primary cultures of skin fibroblasts from systemic sclerosis patients.

Endothelin-1 (ET-1) seems to enhance the pro-fibrotic protein synthesis by skin fibroblasts and its effects are mediated by endothelin-A and B (ETA and ETB) receptors. This study aimed to investigate the effects of ETA and ETB receptor antagonists (ETARA-sitaxsentan and ETA/BRA-bosentan) on type I collagen (COL-1), fibronectin (FN) and fibrillin-1 (FBL-1) synthesis in primary cultures of skin fibroblasts from systemic sclerosis patients. Primary cultures of fibroblasts were obtained from skin biopsies of 6 female systemic sclerosis patients and were treated with ET-1 (100 nM) for 24 and 48 hrs with or without pre-treatment (1 hr) with ETARA (2 µM) or ETA/BRA (10 µM). Primary culture of human scleroderma skin fibroblasts not treated with ET-1 or ET receptor antagonists (ETARA and ETA/BRA) were used as controls. COL-1, FN and FBL-1 synthesis was evaluated by immunocytochemistry and Western blot analysis. Immunocytochemistry and Western blot analysis showed that ET-1 significantly increased COL-1 and FN synthesis at 24 and 48 hrs and FBL-1 synthesis at 48 hrs vs untreated cells. ETARA significantly contrasted the ET-1-mediated increase in COL-1 and FN at 24 hrs as well as COL-1 and FBL-1 at 48 hrs, but not FN synthesis vs ET-1-treated fibroblasts. Conversely, ETA/BRA significantly antagonized the ET-1-mediated overproduction of COL-1 and FN both at 24 and 48 hrs and the FBL-1 synthesis at 48 hrs vs ET-1-treated cells. The single ETARA treatment seems to contrast significantly the increase in COL-1 synthesis, whereas the dual ETA/BRA treatment seems active in significantly antagonizing both COL-1 and FN overproduction induced by ET-1. In conclusion, ET-1 antagonism might have positive effects in contrasting the profibrotic activity of systemic sclerosis skin fibroblasts.

Baroreflex modulation during sleep and in obstructive sleep apnea syndrome.

This review focuses on the complex integration between cardiovascular reflexes and central autonomic influences controlling physiological sleep-dependent changes in arterial blood pressure and heart rate. A brief introduction on the anatomic and functional organization of the arterial baroreflex and the methods available to assess its function in humans is followed by an analysis of the functional interaction between autonomic nervous system and sleep mechanisms at the highest levels of brain organization. An insight into these interactions is important to shed light on the physiopathology of the most frequent complications of obstructive sleep apnea syndrome, such as sustained arterial hypertension, and excessive daytime sleepiness.

Development of a disability scale for myotonic dystrophy type 1.

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests in the literature have evaluated single aspects of DM1 patients, mainly focusing on muscular impairment, without an overall quantification of the different disease-specific neurological features. We developed and validated a new functional scale for DM1 patients based on neuromuscular impairment (NI) and disability. MATERIALS AND METHODS: Thirty-three patients were tested in basal condition, 18 were re-evaluated after therapeutic intervention with mexiletine, and 13 at one year follow-up without treatment. The scale includes 21 ordinal items in four areas: neuropsychology, motricity, myotonia and daily life activities. We evaluated inter- and intra-observer reliability (intraclass correlation coefficient, ICC and Spearman correlations, respectively), internal consistency (Cronbach's alpha), external validity (Spearman correlations between each area and other clinical and objective measurements and scales), and sensitivity to clinical changes after treatment or at follow-up. RESULTS: Our analysis provided good results for inter-observer agreement (ICC = 0.72-0.97), intra-observer reliability, and internal consistency for all areas (Cronbach's α > 0.73). Total score and single area subscores were significantly correlated to objective measurements, disease duration and multisystem involvement. Finally, the scale was sensitive to clinical changes disclosing a significant improvement after treatment in the items assessing myotonia, and also to disease progression showing a significant worsening in all areas but myotonia in untreated patients. DISCUSSION: Our scale provides a new practical measure to evaluate NI and disability of DM1 patients. Further longitudinal studies are warranted to confirm its reliability in tracking disease progression and severity over a longer period of time.

Combined brain voxel-based morphometry and diffusion tensor imaging study in idiopathic restless legs syndrome patients.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel-based morphometry and diffusion tensor imaging (DTI). METHODS: Twenty patients and twenty controls were studied. Voxel-based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL-VBM software tools. For voxel-wise analysis of DTI, tract-based spatial statistics (TBSS) and SPM8 were used. RESULTS: Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses. CONCLUSIONS: Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.

Family recurrence and oligo-anuria predict uremic restless legs syndrome.

OBJECTIVES: To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis (HD). MATERIALS AND METHODS: One hundred and sixty-two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS. RESULTS: Fifty-one patients (32%) currently had RLS (RLS+). RLS+ vs RLS- patients were more frequently women (49% vs 29%, P = 0.012), had first-degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml/24 h, P = 0.001). Low (OR = 8.71, CI = 2.27-33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52-16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44-11.14; P = 0.008), and first-degree relative with RLS (OR = 3.82, CI = 1.21-12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD. CONCLUSION: Positive family history for RLS together with reduced/absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.

[CTLA4-Ig interferes and downregulates the proinflammatory activities of rheumatoid synovial macrophages in monoculture]. / CTLA4-Ig influenza e inibisce le attività proinfiammatorie di macrofagi sinoviali reumatoidi in monocoltura.

OBJECTIVE: CTLA4-Ig, a biologic agent employed in rheumatoid arthritis (RA) treatment, downregulates the immune response and exerts anti-inflammatory effects acting on different cells including dendritic/T cells interaction and directly on osteoclasts. We investigated the anti-inflammatory effects of CTLA4-Ig in primary monocultures of RA synovial macrophages (SM). METHODS: SM were obtained, from 8 RA patients (7 F, 1 M; DAS28>5.2) who underwent therapeutic arthroscopic synoviectomy and were cultured in the absence and in the presence of CTLA4-Ig at the concentration of [500 microg/ml], the most reliable dose related to the previous pharmacological clinical and experimental experiences. Inflammatory cytokine (IL-6, TNFalpha, IL-1beta) expression was evaluated by immunocytochemistry (ICC with relative image analysis), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: ICC analysis revealed that CTLA4-Ig treatment significantly downregulated cytokine expression (p<0.001 for IL-6, TNFalpha and IL-1beta) when compared to untreated RA SM. WB and qRT-PCR confirmed partially the data. CONCLUSIONS: CTLA4-Ig was found to exert a direct and significant anti-inflammatory effect on primary monocultures of RA SM, suggesting a therapeutic power in different phases of the disease activity.

Autonomic innervation in multiple system atrophy and pure autonomic failure.

BACKGROUND: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are both characterised by chronic dysautonomia although presenting different disability and prognosis. Skin autonomic function evaluation by indirect tests has revealed conflicting results in these disorders. Here, the authors report the first direct analysis of skin sympathetic fibres including structure and function in PAF and MSA to ascertain different underlying autonomic lesion sites which may help differentiate between the two conditions. METHODS: The authors studied eight patients with probable MSA (mean age 60±5 years) and nine patients fulfilling diagnostic criteria for PAF (64±8 years). They underwent head-up tilt test (HUTT), extensive microneurographic search for muscle and skin sympathetic nerve activities from peroneal nerve and punch skin biopsies from finger, thigh and leg to evaluate cholinergic and adrenergic autonomic dermal annexes innervation graded by a semiquantitative score presenting a high level of reliability. RESULTS: MSA and PAF patients presented a comparable neurogenic orthostatic hypotension during HUTT and high failure rate of microneurographic trials to record sympathetic nerve activity, suggesting a similar extent of chronic dysautonomia. In contrast, they presented different skin autonomic innervation in the immunofluorescence analysis. MSA patients showed a generally preserved skin autonomic innervation with a significantly higher score than PAF patients showing a marked postganglionic sympathetic denervation. In MSA patients with a long disease duration, morphological abnormalities and/or a slightly decreased autonomic score could be found in the leg reflecting a mild postganglionic involvement. CONCLUSION: Autonomic innervation study of skin annexes is a reliable method which may help differentiate MSA from PAF.

Is migraine a disease?

The migraine attack is a reversible brain dysfunction characterized by pain autonomic symptoms and passive coping strategies consistent with sickness behavior. The migraine attack may be interpreted as an example of genetically determined adaptive behavioral response to internal or external stressors that it is orchestrated by a threatened brain. In this view, the migraine attack itself may not be categorized as a disease, i.e., a deviation from or interruption of the normal structure or function of the brain but it may turn into a disease in an allostatic perspective, when the repeated migraine attacks start maladaptive mechanisms (inefficient turning on or shutting off of the mechanisms underlying the migraine attack) that resulted in a chronic pain of the brain. In future, we should recognize and treat early all the conditions able to transform a normal response of the brain into a morbid state, i.e., we have to categorize migraine not only as a type of headache attack but also as a symptom of different syndromes.

Chronotypes in menstrual migraine: a case-control study.

Migraine attacks have a seasonal, menstrual and circadian periodicity, suggesting a role of chronobiological mechanisms probably related to a hypothalamic involvement. The aim of the study was to evaluate the chronotypes in patients with menstrual migraine, a migraine sub-type with a cyclical recurrence compared to normal female. Ninety-three patients with ICHD-II diagnosis of pure menstrual migraine and menstrually-related migraine were recruited and compared to 85 age-matched healthy women. The Italian version of Morningness-Eveningness Questionnaire was administered to identify circadian preference of our participants. No differences were found regarding the distribution of chronotypes in patients with menstrual migraine and healthy controls. The study did not confirm the presence of a morning and evening preference among migraineurs as previously reported.

Spectral analysis of heart rate variability reveals an enhanced sympathetic activity in narcolepsy with cataplexy.

OBJECTIVE: To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest and during orthostatic stress in narcolepsy with cataplexy (NC). METHODS: Ten NC patients with a hypocretin deficit and 18 control subjects underwent head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing and cold face under controlled laboratory conditions. Heart rate variability (HRV) was analysed during supine rest and HUTT considering the normalized unit of LF and HF power (LFnu; HFnu), using autoregressive (AR) and fast Fourier transform (FFT) algorithms. RESULTS: Cardiovascular changes during HUTT, Valsalva manoeuvre, deep breathing, isometric handgrip and cold face were normal and comparable in the two groups. AR and FFT analysis showed an increased LF/HF ratio in NC patients during supine rest. As expected, LFnu increased and HFnu decreased in the control group during HUTT, but did not change in narcoleptics being comparable to values in the supine condition. CONCLUSIONS: NC patients showed an increased sympathetic drive on heart rate (HR) in the supine condition that did not further increase during HUTT. SIGNIFICANCE: These results suggest the proper functioning of cardiovascular reflexes in NC but support an impairment of HR modulation at rest in favour of an enhanced sympathetic activity.

Increased prevalence of nocturnal smoking in restless legs syndrome (RLS).

OBJECTIVE: We investigated the prevalence of nocturnal smoking (NS) in patients with RLS. METHODS: One hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls, randomly selected from the general population, underwent interviews for the presence of nocturnal smoking and for obsessive-compulsive traits, depression, excessive daytime sleepiness (EDS) and subjective sleep quality. RESULTS: NS was more prevalent in RLS patients than controls (lifetime prevalence: 12% vs. 2%, P=0.012). Patients with NS had more frequently Sleep-Related Eating Disorders (SRED) than patients without NS (83.3% vs. 26.1%, P=0.0002). Pathological and borderline Maudsley Obsessive-Compulsive Inventory (MOCI) values as well as pathological values at the Beck Depression Inventory (BDI) increased from controls to RLS patients without NS to RLS patients with NS (P=0.005 and P=0.01, respectively). CONCLUSIONS: We demonstrate an increased prevalence of NS in patients with RLS, in many cases associated with increased SRED. NS may be associated with psychopathological traits in RLS and may be relevant in the management of RLS patients.

Clinical and neuroimaging evidence of interictal cerebellar dysfunction in FHM2.

We used multimodal magnetic resonance (MR) techniques [brain diffusion-weighted magnetic resonance imaging, diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), (1)H-MRS; and skeletal muscle phosphorous MRS, (31)P-MRS] to investigate interictal brain microstructural changes and tissue energy metabolism in four women with genetically determined familial hemiplegic migraine type 2 (FHM2), belonging to two unrelated families, compared with 10 healthy women. Brain DWI revealed a significant increase of the apparent diffusion coefficient median values in the vermis and cerebellar hemispheres of FHM2 patients, preceding in two subjects the onset of interictal cerebellar deficits. (31)P-MRS revealed defective energy metabolism in skeletal muscle of FHM2 patients, while brain (1)H-MRS showed a mild pathological increase in lactate in the lateral ventricles of one patient and a mild reduction of cortical N-acetyl-aspartate to creatine ratio in another one. Our MRS results showed that a multisystem energy metabolism defect in FHM2 is associated with microstructural cerebellar changes detected by DWI, even before the onset of cerebellar symptoms.

Agrypnia Excitata: a microneurographic study of muscle sympathetic nerve activity.

OBJECTIVE: Agrypnia Excitata (AE) is characterized by autonomic over-activity and cardiovascular fluctuations but direct evidence of sympathoexcitation is lacking. AE is a common feature of acquired (i.e. Morvan's syndrome--MS) and genetic (i.e. fatal familial insomnia--FFI) conditions where a dysfunction of the thalamo-limbic system has been suggested. The aim of this study is to report the first microneurographic recordings of sympathetic activity in acquired and genetic AE to investigate the pattern of sympathetic activation. METHODS: We describe two patients presenting acquired AE (MS) as demonstrated by elevated serum antibody levels to voltage-gated potassium channels and one patient with genetically confirmed FFI. Patients and fifteen sex and age-matched healthy controls underwent microneurography from peroneal nerve to assess muscle sympathetic nerve activity (MSNA) and heart rate (HR). RESULTS: Mean level of resting awake MSNA and HR was significantly increased in patients compared to controls. Patients presented a similar pattern of MSNA with a normal cardiac rhythmicity and a very high burst incidence expressed in approximately each cardiac beat. CONCLUSIONS: Acquired and genetic AE presented a resting awake sympathetic over-activity. SIGNIFICANCE: AE patients may develop high blood pressure and/or cardiovascular instability potentially increasing the morbidity/mortality of the underlying disorders.

Pathologic correlates of diffusion MRI changes in Creutzfeldt-Jakob disease.

OBJECTIVE: The cause of hyperintense magnetic resonance changes and reduced apparent diffusion coefficient (ADC) in specific brain regions of patients with Creutzfeldt-Jakob disease (CJD) is unknown. Our aim was to determine the neuropathologic correlates of antemortem water ADC and normalized T2-weighted changes in patients with CJD. METHOD: Ten patients with CJD and 10 sex- and age-matched healthy controls were studied by DWI and T2-weighted echoplanar MRI. At postmortem, patients with CJD were evaluated for semiquantitative assessment of gliosis and neuronal loss, spongiform changes, and abnormal PrP protein deposition in four cortical regions (occipital, parietal, and temporal cortex, and cingulate gyrus), thalamus, and striatum for a total of 60 regions of interest (ROI). RESULTS: Gliosis and neuronal loss correlated very highly with each other in the 60 ROIs. Where status spongiosus was absent, spongiform change correlated very highly with gliosis and neuronal loss in the cortex, but not in deep gray matter. Spongiform change was also significantly correlated with PrPSc load in both cortical and deep gray ROIs. In deep gray matter, ADC decreased with increasing spongiform change (R2 = 0.78; p < 0.001) and PrPSc load (R2 = 0.51; p = 0.003). In the cortex, ADC decreased with increases in all three, highly correlated, pathologic scores. CONCLUSION: Antemortem reductions in ADC values, typically found in patients with Creutzfeldt-Jakob disease (CJD), are correlated with spongiform changes seen at autopsy. This could be clearly established in the striatum and thalamus of our patients with CJD where the extent of spongiform change was not significantly correlated with gliosis or neuronal loss.