771 research outputs found
Molecular mechanisms behind inherited neurodegeneration of the optic nerve
Inherited neurodegeneration of the optic nerve is a paradigm in neurology, as many forms of isolated or syndromic optic atrophy are encountered in clinical practice. The retinal ganglion cells originate the axons that form the optic nerve. They are particularly vulnerable to mitochondrial dysfunction, as they present a peculiar cellular architecture, with axons that are not myelinated for a long intra-retinal segment, thus, very energy dependent. The genetic landscape of causative mutations and genes greatly enlarged in the last decade, pointing to common pathways. These mostly imply mitochondrial dysfunction, which leads to a similar outcome in terms of neurodegeneration. We here critically review these pathways, which include (1) complex I-related oxidative phosphor-ylation (OXPHOS) dysfunction, (2) mitochondrial dynamics, and (3) endoplasmic reticulum-mito-chondrial inter-organellar crosstalk. These major pathogenic mechanisms are in turn interconnected and represent the target for therapeutic strategies. Thus, their deep understanding is the basis to set and test new effective therapies, an urgent unmet need for these patients. New tools are now available to capture all interlinked mechanistic intricacies for the pathogenesis of optic nerve neuro-degeneration, casting hope for innovative therapies to be rapidly transferred into the clinic and effectively cure inherited optic neuropathies
Biological Responses to Cadmium Stress in Liverwort Conocephalum conicum (Marchantiales)
Oxidative damage (production and localization of reactive oxygen species) and related response mechanisms (activity of antioxidant enzymes), and induction of Heat Shock Protein 70 expression, have been studied in the toxi-tolerant liverwort Conocephalum conicum (Marchantiales) in response to cadmium stress using two concentrations (36 and 360 µM CdCl2). Cadmium dose-dependent production of reactive oxygen species (ROS) and related activity of antioxidant enzymes was observed. The expression level of heat shock protein (Hsp)70, instead, was higher at 36 µM CdCl2 in comparison with the value obtained after exposure to 360 µM CdCl2, suggesting a possible inhibition of the expression of this stress gene at higher cadmium exposure doses. Biological responses were related to cadmium bioaccumulation. Since C. conicum was able to respond to cadmium stress by modifying biological parameters, we discuss the data considering the possibility of using these biological changes as biomarkers of cadmium pollution
Chronic Contained Rupture of an Abdominal Aortic Aneurysm: From Diagnosis to Endovascular Resolution
A male patient, 69 years old, presented with
fever, leucocytosis, and persistent low back pain; he also
had an abdominal aortic aneurysm (AAA), as previously
diagnosed by Doppler UltraSound (US), and was admitted
to our hospital. On multislice computed tomography
(msCT), a large abdominal mass having no definite border
and involving the aorta and both of the psoas muscles was
seen. This mass involved the forth-lumbar vertebra with
lysis, thus simulating AAA rupture into a paraspinal collection;
it was initially considered a paraspinal abscess.
After magnetic resonance imaging examination and culture
of the fluid aspirated from the mass, no infective organisms
were found; therefore, a diagnosisof chronically contained
AAA rupture was made, and an aortic endoprosthesis was
subsequently implanted. The patient was discharged with
decreased lumbar pain. At 12-month follow-up, no evidence
of leakage was observed. To our knowledge, this is
the first case of endoprosthesis implantation in a patient,
who was a poor candidate for surgical intervention due to
renal failure, leucocytosis and high fever, having a chronically
contained AAA ruptured simulatingspodilodiscitis
abscess. Appropriate diagnosis and therapy resolved
potentially crippling pathology and avoided surgical graftrelated
complications.
Keywords Abdominal aortic aneurysm
Endoprosthesis implantation Vertebral erosio
Ada style guide (version 1.1)
Ada is a programming language of considerable expressive power. The Ada Language Reference Manual provides a thorough definition of the language. However, it does not offer sufficient guidance on the appropriate use of Ada's powerful features. For this reason, the Goddard Space Flight Center Ada User's Group has produced this style guide which addresses such program style issues. The guide covers three areas of Ada program style: the structural decomposition of a program; the coding and the use of specific Ada features; and the textural formatting of a program
A multi-scale framework to predict damage initiation at martensite/ferrite interface
Martensite/ferrite (M/F) interface damage largely controls failure of dual-phase (DP) steels. In order to predict the failure and assess the ductility of DP steels, accurate models for the M/F interfacial zones are needed. Several M/F interface models have been proposed in the literature, which however do not incorporate the underlying microphysics. It has been recently suggested that (lath) martensite substructure boundary sliding dominates the M/F interface damage initiation and therefore should be taken into account. Considering the computationally infeasibility of direct numerical simulations of statistically representative DP steel microstructures, while explicitly resolving the interface microstructures and the sliding activity, a novel multi-scale approach is developed in this work. Two scales are considered: the DP steel mesostructure consisting of multiple lath martensite islands embedded in a ferrite matrix, and the microscopic M/F interfacial zone unit cell resolving the martensite substructure. Based on the emerging microscopic damage initiation pattern, an effective indicator for the M/F interface damage initiation is determined from the interface microstructural unit cell response, along with the effective sliding in this unit cell. Relating these two effective quantities for different interface microstructural configurations leads to an effective mesoscale model relating the interface damage indicator to the sliding activity of the martensite island in terms of the mesoscopic kinematics. This microphysics-based M/F interface damage indicator model, which could not be envisioned a-priori, is fully identified from a set of interfacial unit cell simulations, thus enabling the efficient prediction of interface damage initiation at the mesoscale. The capability of the developed effective model to predict the mesoscopic M/F interface damage initiation is demonstrated on an example of a realistic DP steel mesostructure
The "Safari" technique to perform difficult subintimal infragenicular vessels
The purpose of this study was to describe the efficacy of
planned combined subintimal arterial flossing with antegrade–
retrograde intervention (SAFARI) to obtain the precise
recanalization of the patent portion of a distal runoff
vessel in critical limb ischemia (CLI) patients presenting
long occlusions involving the popliteal trifurcation. Four
patients at risk of limb loss due to long occlusions involving
the leg vessel tree and not suitable for a surgical bypass
were treated by the subintimal antegrade and retrograde
(posterior tibial or anterior tibial artery) approach. The
patent portion of the runoff vessel was previously assessed
by magnetic resonance angiography (MRA) and directly
punctured under Doppler ultrasound (US) guidance. A
subintimal channel rendezvous was performed to allow
snaring of the guidewires. Subsequently, a balloon dilatation
was performed without stent deployment. All patients were
successfully recanalized and had complete healing of the
limb lesions. At the 12-month follow-up all patients showed
clinical improvement with no major complications related to
the procedure. This combined antegrade and retrograde
subintimal approach is currently an excellent endovascular
option in patients with long occlusions extending onto the
leg vessels trifurcation and at risk of limb loss.
Key words: Critical limb ischemia—Subintimal technique—
Popliteal branches—Retrograde acces
Revisiting the martensite/ferrite interface damage initiation mechanism:The key role of substructure boundary sliding
Martensite/ferrite (M/F) interface damage plays a critical role in controlling failure of dual-phase (DP) steels and is commonly understood to originate from the large phase contrast between martensite and ferrite. This however conflicts with a few, recent observations, showing that considerable M/F interface damage initiation is often accompanied by apparent martensite island plasticity and weak M/F strain partitioning. In fact, martensite has a complex hierarchical structure which induces a strongly heterogeneous and orientation-dependent plastic response. Depending on the local stress state, (lath) martensite is presumed to be hard to deform based on common understanding. However, when favourably oriented, substructure boundary sliding can be triggered at a resolved shear stress which is comparable to that of ferrite. Moreover, careful measurements of the M/F interface structure indicate the occurrence of sharp martensite wedges protruding into the ferrite and clear steps in correspondence with lath boundaries, constituting a jagged M/F interfacial morphology that may have a large effect on the M/F interface behaviour. By taking into account the substructure and morphology features, which are usually overlooked in the literature, this contribution re-examines the M/F interface damage initiation mechanism. A systematic study is performed, which accounts for different loading conditions, phase contrasts, residual stresses/strains resulting from the preceding martensitic phase transformation, as well as the possible M/F interfacial morphologies. Crystal plasticity simulations are conducted to include inter-lath retained austenite (RA) films enabling the substructure boundary sliding. The results show that the substructure boundary sliding, which is the most favourable plastic deformation mode of lath martensite, can trigger M/F interface damage and hence control the failure behaviour of DP steels. The present finding may change the way in which M/F interface damage initiation is understood as a critical failure mechanism in DP steels
Right ventricular morpho-functional remodelling in never treated hypertensives: role of aortic pressure and bi-ventricular parameters
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Role of cysteine in regulating morphogenesis and mitochondrial activity in the dimorphic fungus Histoplasma capsulatum.
Relationship between regional fat distribution and hypertrophic cardiomyopathy phenotype
Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is characterized by heterogeneous phenotypic expression. Body mass index has been associated with LV mass and heart failure symptoms in HCM. The aim of our study was to investigate whether regional (trunk, appendicular, epicardial) fat distribution and extent could be related to hypertrophy severity and pattern in HCM
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