Association between non-alcoholic fatty liver disease and subclinical hypothyroidism in children with obesity.

PURPOSE: We aimed (i) evaluating the relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function tests, (ii) testing if the relationship between NAFLD and thyroid dysfunction could be driven by the obesity and the IR degree, and (iii) exploring the influence of the patatin-like phospholipase domain-containing protein-3 (PNPLA3) I148M and the transmembrane 6 superfamily member 2 (TM6SF2) E167K polymorphisms on the association between NAFLD and thyroid function in children. METHODS: We examined 2275 children and adolescents with obesity. Subclinical hypothyroidism (SH) was defined by thyroid-stimulating hormone (TSH) > 4.2 µUI/ml with normal fT3 and fT4. RESULTS: Children with NAFLD showed higher SH prevalence than those without NAFLD (15.7% Vs 7.4%;p = 0.001) and showed an adjusted odds ratio (aOR) to have SH of 1.68 (95% CI:1.01-2.80;p = 0.04) while patients with SH had an aOR to show NAFLD of 2.13(95% CI:1.22-3.73;p = 0.008). Patients having severe obesity and IR degree presented an aOR to show both NAFLD and SH of 3.61 (95% CI:1.78-7.33;p < 0.0001). Subjects with NAFLD carrying the TM6SF2 167 K allele had lower TSH levels than non-carriers (p = 0.03) and showed an aOR to have SH of 0.10 (95% CI: 0.01-0.79;p = 0.02). No differences were found in carriers of the PNPLA3 148 M allele. A general linear model for TSH variance showed a significant association of TSH with TM6SF2 genotypes only in the NAFLD group (p = 0.001). CONCLUSION: Children with obesity and NAFLD presented increase risk of SH and vice versa likely due to the adverse effect of duration of obesity, obesity degree, and IR. The TM6SF2 E167K exerts a protective role against SH in children with obesity and NAFLD.

Docosahexaenoic acid promotes oligodendrocyte differentiation via PPAR-γ signalling and prevents tumor necrosis factor-α-dependent maturational arrest.

Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-dependent transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). In this study, we used primary oligodendrocyte progenitor (OP) cultures from neonatal rat brain to investigate whether DHA could influence OP maturation and directly promote myelination, as previously reported for selective PPAR-γ agonists. We show that, similarly to the selective PPAR-γ agonist pioglitazone (PGZ), DHA promotes OP maturation and counteracts the maturational arrest induced by TNF-α, used to mimic inflammatory conditions. The PPAR-γ antagonist GW9662 prevented both DHA-induced OP maturation and PPAR-γ nuclear translocation, supporting the hypothesis that DHA acts through the activation of PPAR-γ. In addition, both PGZ and DHA induced the phosphorylation of extracellular signal-regulated-kinase 1-2 (ERK1/2), in a PPAR-γ-dependent manner. ERK1/2 activity is known to regulate the transition from OPs to immature oligodendrocytes and the presence of specific inhibitors of ERK1/2 phosphorylation (U0126 or PD98059) prevented the differentiating effects of both DHA and PGZ. These results indicate that DHA might influence the process of OP maturation through its PPAR-γ agonistic activity and provide novel molecular mechanisms for the action of this dietary fatty acid, further supporting the nutritional intervention in demyelinating diseases such as multiple sclerosis.

The role of intracranial hypertension in the chronification of migraine.

Besides a similar clinical presentation, idiopathic intracranial hypertension (IIH) and chronic migraine (CM) also share relevant risk factors, show a higher prevalence of allodynic symptoms and both respond to topiramate. Moreover, sinus stenosis, a radiological marker of IIH, in CM patients is much more prevalent than expected. As a consequence of these striking similarities, IIH without papilledema (IIHWOP) may be easily misdiagnosed as CM. Actually, IIHWOP has been found in up to 14 % of CM clinical series. Considering that, on one hand, an asymptomatic sinus stenosis-associated raised intracranial pressure (ICP) may be highly prevalent in the general population, and on the other, that IIH clinical presentation with chronic headache may require a migraine predisposition, we have proposed that an overlooked IIHWOP could represent a risk factor for migraine progression. This hypothesis prompted us to investigate the prevalence of IIHWOP and its possible role in the process of migraine chronification in a consecutive series of CM patients selected for unresponsiveness to medical treatment and evidence of significant sinus stenosis. The main finding of our study is that the large majority of such patients actually suffer from a chronic headache secondary to IIHWOP. This implies that an IIHWOP mimicking CM is much more prevalent than believed, is commonly misdiagnosed as CM on the basis of ICHD criteria and is strictly predicted by refractoriness to preventive treatments. However, our data fully comply with the alternative hypothesis that an overlooked IIHWOP, although highly prevalent amongst healthy individuals, in migraine-prone subjects is a powerful (and modifiable) risk factor for the progression and the refractoriness of pain. The normalization of ICP by even a single LP with CSF withdrawal may be effective in a significant proportion of patients with a long history of refractory chronic headache, who represent about one-fifth of the patients screened in our study. We suggest that IIHWOP should be considered in all patients with almost daily migraine pain, with evidence of sinus stenosis and unresponsive to medical treatment, referred to specialized headache clinics.

The lesson of chronic migraine.

The hypothesis that central sensitization/allodynia is the common final mechanism responsible for the progression of migraine pain is supported by the possibility of tracing back to allodynic mechanisms the action of the main risk factors for chronic migraine validated by the recent literature. The comorbidity between migraine and idiopathic intracranial hypertension without papilledema is emerging as a new, commonly overlooked risk factor for migraine progression whose putative mechanism might also converge on the sensitization of central pain pathways. If headache progression always occurs at the end of a pathogenetic sequence typical of an individual susceptibility to allodynia, then the primary character of chronic migraine might be debated. Allodynia is not specific to migraine but is implied in the progressive amplification of pain after repeated stimuli, a universal adaptive phenomenon. Being largely conditioned by the individual comorbidity profile, allodynia may only in part be defined as primary in itself. Many migraine comorbid conditions, including a hidden idiopathic intracranial hypertension without papilledema, may emphasize susceptibility to allodynia and promote chronic migraine. These factors and comorbid conditions require to be individually assessed and adequately treated to optimize the therapeutic response.

Recurrent epistaxis following stabbing headache responsive to acetazolamide.

The co-occurrence of epistaxis and headache is not uncommon in migraine patients, although only few case reports have been published. A trigeminovascular activation may be causally involved although the exact mechanisms linking epistaxis and migraine remain unclear. Significant dural sinus stenosis may sustain or worsen an increased cerebral venous pressure and is considered a radiological predictor of idiopathic intracranial hypertension. We report a 49-year-old female patient with chronic migraine associated to stabbing headache-like attacks followed by epistaxis and by the resolution or the significant improvement of pain. As she also reported adjunctive symptoms suggestive of raised intracranial pressure and showed a bilateral narrowing of transverse sinuses at MR-venography, a possible intracranial hypertension was hypothesized despite the lack of papilledema. Acetazolamide 250 mg twice/day was added to therapy and the patient reported sudden reduction of headache severity and frequency and complete resolution of both the stabbing pain and the recurrent epistaxis, maintained for 5 months. At treatment discontinuation she complained the worsening of migraine headache and the reoccurrence of the superimposed stabbing pain followed by epistaxis. The mechanism linking the sequential occurrence of painful stabs, epistaxis and relief from pain with raised intracranial pressure in our patients remains unclear. We speculate that the sudden reopening of collapsed collateral veins of the anterior venous circle, possibly prompted by periodic waves of central venous hypertension coupled with intracranial hypertensive peaks, could explain the unusual strict time succession of painful stabs, epistaxis, and subsequent resolution of pain.

Cortical spreading depression and central pain networks in trigeminal nuclei modulation: time for an integrated migraine pathogenesis perspective.

The role of the cortical spreading depression (CSD)-dependent trigeminovascular activation in migraine etiopathogenesis, long considered paradigmatic, has remained substantially unproven in humans. The parallel advancement of functional neuroimaging techniques promoted the extensive exploration of the brain networks involved in pain processing in search of a possible central migraine generator. However, despite initial enthusiasms, it has not been possible to clarify whether the functional central "markers" of pain observed in primary headaches could be considered as causative or just the neural correlates of the ongoing pain. Nonetheless, our knowledge on the complex interactions between CSD, neurogenic inflammation, peripheral trigeminovascular input, central cortico-trigeminal nuclei direct modulation and pain processing and limbic system networks has enormously grown, allowing the reconceptualisation of migraine from a neurovascular to a pure neurolimbic pain disorder, therefore relocating it in the much broader frame of the brain and whole organism homeostatic control. In this work, the available evidences currently supporting the relevance of CSD, of peripheral trigeminovascular input and of direct cortico-trigeminal nuclei modulation in migraine pathogenesis are reviewed in the light of a possible integrated migraine etiopathogenetic perspective.

Primary stabbing headache: a new dural sinus stenosis-associated primary headache?

Primary stabbing headache (PSH) is a primary syndrome of unknown aetiology, characterised by brief, jabbing stabs predominantly felt in the orbital, temporal and parietal areas, whose frequency may vary from one to many per day, usually responding to indomethacin. PSH frequency in the general population is not well defined, but recent evidence suggests it could be more frequent than previously thought. In clinical series, PSH incidence was 33/100,000 per year, while in a population study 35.2 % prevalence was found. PSH was previously described as isolated or associated to other headache syndromes, most frequently with migraine. There is evidence that an idiopathic intracranial hypertension without papilledema, a condition usually associated to significant stenosis of dural sinuses (93 % sensitivity and specificity), is much more prevalent than believed and may run asymptomatically in up to 11 % of otherwise healthy individuals. In migrainous prone people, a sinus stenosis-associated intracranial hypertension without papilledema (ss-IHWOP) comorbidity may represent a powerful risk factor for progression of pain. Besides migraine, significant sinus stenosis has been found overrepresented also in chronic tension type headache as well as in exertional, cough, sexual activity-associated headaches (all indomethacin responsive primary headaches) and in altitude headache (an acetazolamide responsive condition). To explore the possible association between venous outflow disturbances and PSH, we retrospectively investigated the co-occurrence of sinus venous stenosis in patients referring to our headache centre since 2004 diagnosed with PSH who completed the diagnostic protocol. Out of 50 consecutive patients reporting PSH as the main or as accessory complaint, 8 (6 females, 2 males) performed MR venography (MRV). All MRV revealed significant unilateral or bilateral sinus stenosis. Mean age at PSH onset was 35.3 ± 18.9 years (range 11-67 years). Duration of attacks ranged 1-3 s. Median daily frequency of attacks was 4 (range 2-20); median number of days per month with PSH presentation was 14 (range 4-30). Six patients described attacks in temporal or parietal areas, one at the top of the head, and one in the occipital area. Only one patient had isolated PSH; all the others were diagnosed also with migraine without aura. Seven out of eight patients responded to indomethacin 75 mg/die, and one to topiramate 100 mg/die. Interestingly, both drugs share with acetazolamide a CSF pressure lowering effect. Our findings indicate that PSH is associated with central sinus stenosis and suggest that an undiagnosed ss-IHWOP might be involved in PSH pathogenesis.

Maternal suboptimal selenium intake and low-level lead exposure affect offspring's microglial immune profile and its reactivity to a subsequent inflammatory hit.

Micronutrients such as selenium (Se) are essentials since prenatal life to support brain and cognitive development. Se deficiency, which affects up to 1 billion people worldwide, can interact with common adverse environmental challenges including (Pb), exacerbating their toxic effects. Exploiting our recently validated rat model of maternal Se restriction and developmental low Pb exposure, our aims were to investigate: (i) the early consequences of suboptimal Se intake and low-Pb exposure on neuroinflammation in neonates' whole brains; (ii) the potential priming effect of suboptimal Se and low-Pb exposure on offspring's glial reactivity to a further inflammatory hit. To these aims female rats were fed with suboptimal (0.04 mg/kg; Subopt) and optimal (0.15 mg/kg; Opt) Se dietary levels throughout pregnancy and lactation and exposed or not to environmentally relevant Pb dose in drinking water (12.5 µg/mL) since 4 weeks pre-mating. We found an overall higher basal expression of inflammatory markers in neonatal brains, as well as in purified microglia and organotypic hippocampal slice cultures, from the Subopt Se offspring. Subopt/Pb cultures were highly activated than Subopt cultures and showed a higher susceptibility to the inflammatory challenge lipopolysaccharide than cultures from the Opt groups. We demonstrate that even a mild Se deficiency and low-Pb exposure during brain development can influence the neuroinflammatory tone of microglia, exacerbate the toxic effects of Pb and prime microglial reactivity to subsequent inflammatory stimuli. These neuroinflammatory changes may be responsible, at least in part, for adverse neurodevelopmental outcomes.

Pain as an evolutionary necessity.

The proposed title "Pain as an evolutionary necessity" could lead to a broad debate with implications covering many chapters of the medicine and particularly of clinical neurology. In the present perspective, the discussion will focus on migraine and cluster headache chosen as elective examples of biological and not only clinical conditions, that unveil the bond between pain and necessity. Migraine, cluster headache, and perhaps other primary headaches begin to be depicted in terms of recurrent activation of innate bio-behavioral specific patterns, with a crucial and highly conserved evolutionarily adaptive significance. The pan-mammalian sickness behavior and the fight or flight response, selectively activated by different kinds of pain, are here proposed as paradigmatic of migraine and cluster headache attacks associated behaviors, allowing to reformulate these forms as the inappropriate recurrent presentation of coordinated allostatic processes, modeled along million of years of natural evolution. In this light, all the multifaceted characteristics of migraine and cluster headache attacks can be reinterpreted as complex and integrated allostatic defensive reactions to an inescapable or to an escapable pain, respectively aimed to the restoration of biologic homeostasis through a temporary disengagement from active interaction with environment (migraine associated sickness behavior) or, on the contrary, to promote the coordinated biological changes preparatory to emergency and defensive behaviors (cluster headache-related fight or flight response).

Underdiagnosis and undertreatment of migraine in Italy: a survey of patients attending for the first time 10 headache centres.

The aim of this study was to asses the clinical features, pattern of healthcare and drug utilization of migraine patients attending 10 Italian headache centres (HC). Migraine is underdiagnosed and undertreated everywhere throughout the world, despite its considerable burden. Migraine sufferers often deal with their problem alone using self-prescribing drugs, whereas triptans are used by a small proportion of patients. All patients attending for the first time 10 Italian HCs over a 3-month period were screened for migraine. Migraine patients underwent a structured direct interview about previous migraine diagnosis, comorbidity, headache treatments and their side-effects and healthcare utilization for migraine. Patient satisfaction with their usual therapy for the migraine attack was evaluated with the Migraine-Assessment of Current Therapy (ACT) questionnaire. The quality of life of migraine patients was assessed by mean of Short Form (SF)-12 and Migraine-Specific Quality of life (MSQ) version 2.1 questionnaires. Of the 2675 patients who attended HCs for the first time during the study period, 71% received a diagnosis of migraine and the first 953 subjects completed the study out of 1025 patients enrolled. Only 26.8% of migraine patients had a previous diagnosis of migraine; 62.4% of them visited their general practitioner (GP) in the last year, 38.2% saw a specialist for headache, 23% attended an Emergency Department and 4.5% were admitted to hospital for migraine; 82.8% of patients used non-specific drugs for migraine attacks, whereas 17.2% used triptans and only 4.8% used a preventive migraine medication. Triptans were used by 46.4% of patients with a previous diagnosis of migraine. About 80% of migraine patients took over-the-counter medications. The Migraine-ACT revealed that 60% of patients needed a change in their treatment of migraine attacks, 85% of whom took non-specific drugs. Both the MSQ version 2.1 and the SF-12 questionnaires indicated a poor quality of life of most patients. Migraine represents the prevalent headache diagnosis in Italian HCs. Migraine is still underdiagnosed in Italy and migraine patients receive a suboptimal medical approach in our country, despite the healthcare utilization of migraine subjects being noteworthy. A cooperative network involving GPs, neurologists and headache specialists is strongly desirable in order to improve long-term migraine management in Italy.

Redefining primary headaches.

In the light of the pathophysiologic knowledge acquired in the recent years, a tentative redefinition is now possible of some types of headache until now defined as idiopathic, and indistinctly described as primary headaches. Cluster headache and trigeminal neuralgia are known examples of diseases classified as primary, which are, in contrast, well-defined diseases to be distinguished from headaches without any recognized anatomic site of lesion or pathogenesis. Another still debated condition, chronic migraine, is proposed here as the consequence of "processes" to be ascribed to mechanisms activated by other comorbid conditions. The observations supporting the possibility that allodynia represents the implicit process leading to pain progression, which occurs in some migraineurs, are discussed.

Towards a mixed reality environment for preoperative planning of cardiac surgery.

We present a novel approach to studying physical heart models by coupling them with virtual 3D representations in a mixed reality environment. The limitations of standalone physical models (non-interactive, static) are overcome by the corresponding virtual models, which in turn become more natural to interact with. The potential of this approach is exemplified by a setup which enables cardiac surgeons to interactively trace the mitral annulus, a part of the cardiac skeleton playing a vital role in mitral valve surgery. We present results of a pilot study and discuss ways of improving and extending the system. The described mixed reality environment could easily be adapted to other fields and thus has the potential to become a new tool for investigating 3D medical data.

NGF promotes microglial migration through the activation of its high affinity receptor: modulation by TGF-beta.

Activation and mobilization of microglia are early events in the majority of brain pathologies. Among the signalling molecules that can affect microglial behaviour, we investigated whether nerve growth factor (NGF) was able to influence microglial motility. We found that NGF induced chemotaxis of microglial cells through the activation of TrkA receptor. In addition, NGF chemotactic activity was increased in the presence of low concentrations (< or =0.2 ng/ml) of transforming growth factor-beta (TGF-beta), which at this concentration showed chemotactic activity per se. On the contrary, NGF-induced microglial migration was reduced in the presence of chemokinetic concentration of TGF-beta (> or =2 ng/ml). Finally, both basal and NGF-induced migratory activity of microglial cells was increased after a long-term exposure of primary mixed glial cultures to 2 ng/ml of TGF-beta. Our observations suggest that both NGF and TGF-beta contribute to microglial recruitment. The chemotactic activities of these two pleiotropic factors could be particularly relevant during chronic diseases in which recruited microglia remove apoptotic neurons in the absence of a typical inflammatory reaction.

[Three-dimensional echocardiography in cardiac surgery. Current status and perspectives]. / Klinischer Einsatz der 3D-Echokardiographie in der Herzchirurgie. Aktueller Stand und Perspektiven.

Three-dimensional (3D) echocardiography is a new imaging technique that can provide useful information about cardiovascular morphology, pathology, and function. Recent refinements in instrumentation, data acquisition, post-processing, and computation speed allow 3D echocardiography to play an important role in cardiac imaging. These modalities provide comprehensive information on ventricular and valve morphology and function. Combined with 3D color Doppler sonography, further assessment of valvular function and determination of flow in the left ventricular outflow tract and cross-septal defects are now possible. Three-dimensional color flow imaging also makes echocardiography accurate for assessing the severity of mitral regurgitation. The purpose of this review is to describe technical developments in 3D echocardiography and its clinical application in cardiac surgery. Moreover, based on clinical studies at our centre, we describe the morphology of the mitral valve, its flow pattern, and function of the mitral annulus.

Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis.

OBJECTIVE: The aim of the study is to evaluate the effect of moderate Sicilian red wine consumption on cardiovascular risk factors and, in particular, on some inflammatory biomarkers. METHODS: A total of 48 subjects of both sexes who were nondrinkers or rare drinkers of moderate red wine were selected and randomly subdivided into two groups assigned to receive with a crossover design a Sicilian red wine (Nero d'Avola or Etna Torrepalino) during meals: Group A (n = 24), in whom the diet was supplemented for 4 weeks with 250 ml/day of red wine, followed by 4 weeks when they returned to their usual wine intake; and Group B (n = 24), in whom the usual wine intake was maintained for 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml/day of red wine. The following were values measured in all tests: blood glucose, total and HDL-cholesterol and triglycerides, LDL-cholesterol, LDL/HDL ratio, apolipoproteins A1 and B, Lp(a), plasma C-reactive protein, TGFbeta1, D-Dimer, Factor VII , PAl Ag, t-PA Ag, fibrinogen, oxidized LDL Ab, total plasma antioxidant capacity. RESULTS: At the end of the red wine intake period, LDL/HDL, fibrinogen, factor VII, plasma C-reactive protein and oxidized LDL Ab were significantly decreased, while HDL-C, Apo A1,TGFbeta1, t-PA, PAI and total plasma antioxidant capacity were significantly increased. CONCLUSIONS: Our results show a positive effect of two Sicilian red wines on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet.

One-year atorvastatin treatment in hypercholesterolemic patients with or without carotid artery disease.

AIM: Statins are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of premature cardiovascular events including myocardial infarction, stroke, and surgical revascularization. METHODS: A 1-year open-label study was conducted to test the efficacy and tolerability of Atorvastatin titrated to the target, in proven FH patients and to evaluate certain inflammatory parameters. One hundred and two FH patients (44 men and 58 women; mean age 58.7+/-3.6 years) were included in the study. After evaluation using the B-mode duplex scanning system of extracranial carotid arteries, the patients were divided into two groups: Group 1 (15 men, 25 women) with carotid plaques or intima-media thickness (IMT) greater than 0.95 mm and Group 2 (30 men, 32 women) without carotid plaques or IMT less than 0.95 mm. After a 6-week hypolipemic diet phase all the patients were treated with atorvastatin titrated to achieve a low density lipoprotein (LDL-C) <100 mg/dL. Patients with carotid lesions were also submitted to an oral fixed dose of aspirin 100 mg/day. RESULTS: In patients without and with carotid lesions, atorvastatin treatment (mean dosage: 23.5 mg/day) reduced triglycerides by 8.7% (P<0.005) and 10.6% (P<0.005), total cholesterol by 41.5% (P<0.005) and 42.6% (P<0.005), LDL-C by 55.8% (P<0.005) and 57.3% (P<0.005) and apolipoprotein B by 38.3% (P<0.005) and 37.2% (P<0.005) respectively, and increased the mean levels of high density lipoprotein cholesterol (HDL-C) by 8.7% (P<0.005) and 11% (P<0.005), and apolipoprotein A-I by 3.2% (P<0.05) and 3.3%, respectively. In both groups of patients the mean decrease (52 weeks) of fibrinogen was 19.8% (P<0.005) and 10.4% (P<0.005), respectively and of high sensitivity C-reactive protein (hs-CRP), 36.2% (P<0.005) and 38.2% (P<0.005), respectively. No variation of the parameters of safety and clinical tolerability of the drugs administered was observed. No variation in hematocrit in the patients taking ASA treatment was observed. CONCLUSIONS: In FH patients, 1-year atorvastatin treatment titrated to the target (LDL-C <100 mg/dL) was well tolerated and improved serum lipid levels and inflammatory parameters.

Comprehensive patient-specific information preprocessing for cardiac surgery simulations.

PURPOSE: Patient-specific biomechanical simulations of the behavior of soft tissue gain importance in current surgery assistance systems as they can provide surgeons with valuable ancillary information for diagnosis and therapy. In this work, we aim at supporting minimally invasive mitral valve reconstruction (MVR) surgery by providing scenario setups for FEM-based soft tissue simulations, which simulate the behavior of the patient-individual mitral valve subject to natural forces during the cardiac cycle after an MVR. However, due to the complexity of these simulations and of their underlying mathematical models, it is difficult for non-engineers to sufficiently understand and adequately interpret all relevant modeling and simulation aspects. In particular, it is challenging to set up such simulations in automated preprocessing workflows such that they are both patient-specific and still maximally comprehensive with respect to the model. METHODS: In this paper, we address this issue and present a fully automated chain of preprocessing operators for setting up comprehensive, patient-specific biomechanical models on the basis of patient-individual medical data. These models are suitable for FEM-based MVR surgery simulation. The preprocessing methods are integrated into the framework of the Medical Simulation Markup Language and allow for automated information processing in a data-driven pipeline. RESULTS: We constructed a workflow for holistic, patient-individual information preprocessing for MVR surgery simulations. In particular, we show how simulation preprocessing can be both fully automated and still patient-specific, when using a series of dedicated MVR data analytics operators. The outcome of our operator chain is visualized in order to help the surgeon understand the model setup. CONCLUSION: With this work, we expect to improve the usability of simulation-based MVR surgery assistance, through allowing for fully automated, patient-specific simulation setups. Combined visualization of the biomechanical model setup and of the corresponding surgery simulation results fosters the understandability and transparency of our assistance environment.

Three-dimensional color Doppler: a clinical study in patients with mitral regurgitation.

OBJECTIVES: The purpose of this study was to assess the clinical feasibility of three-dimensional (3D) reconstruction of color Doppler signals in patients with mitral regurgitation. BACKGROUND: Two-dimensional (2D) color Doppler has limited value in visualizing and quantifying asymmetric mitral regurgitation. Clinical studies on 3D reconstruction of Doppler signals in original color coding have not yet been performed in patients. We have developed a new procedure for 3D reconstruction of color Doppler. METHODS: We studied 58 patients by transesophageal 3D echocardiography. The jet area was assessed by planimetry and the jet volumes by 3D Doppler. The regurgitant fractions, the volumes, and the angiographic degree of mitral regurgitation were assessed in 28 patients with central jets and compared with those of 30 patients with eccentric jets. RESULTS: In all patients, jet areas and jet volumes significantly correlated with the angiographic grading (r = 0.73 and r = 0.90), the regurgitant fraction (r = 0.68 and r = 0.80) and the regurgitant volume (r = 0.66 and r = 0.90). In patients with central jets, significant correlations were found between jet area and angiography (r = 0.86), regurgitant fraction (r = 0.64) and regurgitant volume (r = 0.78). No significant correlations were found between jet area and angiography (r = 0.53), regurgitant fraction (r = 0.52) and regurgitant volume (r = 0.53) in the group of patients with eccentric jets. In contrast, jet volumes significantly correlated with angiography (r = 0.90), regurgitant fraction (r = 0.75) and regurgitant volume (r = 0.88) in the group of patients with eccentric jets. CONCLUSIONS: Three-dimensional Doppler revealed new images of the complex jet geometry. In addition, jet volumes, assessed by an automated voxel count, independent of manual planimetry or subjective estimation, showed that 3D Doppler is also capable of quantifying asymmetric jets.

Peroxisome proliferator activated receptor-γ agonists protect oligodendrocyte progenitors against tumor necrosis factor-alpha-induced damage: Effects on mitochondrial functions and differentiation.

The activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) is known to exert anti-inflammatory and neuroprotective effects and PPAR-γ agonists are considered potential therapeutic agents in brain diseases including those affecting myelin. In demyelinating diseases such as multiple sclerosis (MS), inflammation is one of the causes of myelin and axonal damage. Oligodendrocyte (OL) differentiation is highly dependent on mitochondria, which are major targets of inflammatory insult. Here we show that PPAR-γ agonists protect OL progenitors against the maturational arrest induced by the inflammatory cytokine TNF-α by affecting mitochondrial functions. We demonstrate that the inhibition of OL differentiation by TNF-α is associated with i) increased mitochondrial superoxide production; ii) decreased mitochondrial membrane potential (mMP); and iii) decreased ADP-induced Ca(2+) oscillations, which we previously showed to be dependent on efficient mitochondria. The TNF-α effects were comparable to those of the mitochondrial toxin rotenone, further suggesting that TNF-α damage is mediated by mitochondrial function impairment. PPAR-γ agonists protected OL progenitors against the inhibitory activities of both TNF-α and rotenone on mMP, mitochondrial ROS production, Ca(2+) oscillations and OL differentiation. Finally, the PPAR-γ agonist pioglitazone increased the expression of PGC-1α (a mitochondrial biogenesis master regulator), UCP2 (a mitochondrial protein known to reduce ROS production), and cytochrome oxidase subunit COX1. These findings confirm the central role of mitochondria in OL differentiation and point to mitochondria as major targets of PPAR-γ agonist protection against TNF-α damage.

Proposal of a new method for the use of the Rydel-Seiffer tuning fork in the screening of diabetic polyneuropathy. A pilot study.

We investigated the usefulness of a new examiner-independent method based on the duration of vibration sensation following the placement of the Rydel-Seiffer tuning fork over the dorsum of the interphalangeal hallux joint. This method demonstrated the same diagnostic efficacy as the Rydel-Seiffer method coupled with greater ease of use.