Magnetic resonance imaging scoring system of the lower limbs in adult patients with suspected idiopathic inflammatory myopathy.

PURPOSE: We aim to propose a visual quantitative score for muscle edema in lower limb MRI to contribute to the diagnosis of idiopathic inflammatory myopathy (IIM). MATERIAL AND METHODS: We retrospectively evaluated 85 consecutive patients (mean age 57.4 ± 13.9 years; 56.5% female) with suspected IIM (muscle weakness and/or persistent hyper-CPK-emia with/without myalgia) who underwent MRI of lower limbs using T2-weighted fast recovery-fast spin echo images and fat-sat T2 echo planar images. Muscle inflammation was evaluated bilaterally in 11 muscles of the thigh and eight muscles of the leg. Edema in each muscle was graded according to a four-point Likert-type scale adding up to 114 points ([11 + 8)] × 3 × 2). Diagnostic accuracy of the total edema score was explored by assessing sensitivity and specificity using the area under the ROC curve. Final diagnoses were made by a multidisciplinary Expert Consensus Panel applying the Bohan and Peter diagnostic criteria whenever possible. RESULTS: Of the 85 included patients, 34 (40%) received a final diagnosis of IIM (IIM group) while 51 (60%) received an alternative diagnosis (non-IIM group). A cutoff score ≥ 18 was able to correctly classify patients having an IIM with an area under the curve of 0.85, specificity of 96%, and sensitivity of 52.9%. CONCLUSION: Our study demonstrates that a quantitative MRI score for muscle edema in the lower limbs (thighs and legs) aids in distinguishing IIM from conditions that mimic it.

Condition Monitoring of Induction Machines: Quantitative Analysis and Comparison.

In this paper, a diagnostic procedure for rotor bar faults in induction motors is presented, based on the Hilbert and discrete wavelet transforms. The method is compared with other procedures with the same data, which are based on time-frequency analysis, frequency analysis and time domain. The results show that this method improves the rotor fault detection in transient conditions. Variable speed drive applications are common in industry. However, traditional condition monitoring methods fail in time-varying conditions or with load oscillations. This method is based on the combined use of the Hilbert and discrete wavelet transforms, which compute the energy in a bandwidth corresponding to the maximum fault signature. Theoretical analysis, numerical simulation and experiments are presented, which confirm the enhanced performance of the proposed method with respect to prior solutions, especially in time-varying conditions. The comparison is based on quantitative analysis that helps in choosing the optimal trade-off between performance and (computational) cost.

Molecular biomarkers correlate with brain grey and white matter changes in patients with mitochondrial m.3243A > G mutation.

INTRODUCTION: The mitochondrial DNA (mtDNA) m.3243A > G mutation in the MT-TL1 gene results in a multi-systemic disease, that is commonly associated with neurodegenerative changes in the brain. METHODS: Seventeen patients harboring the m3243A > G mutation were enrolled (age 43.1 ± 11.4 years, 10 M/7F). A panel of plasma biomarkers including lactate acid, alanine, L-arginine, fibroblast growth factor 21 (FGF-21), growth/differentiation factor 15 (GDF-15) and circulating cell free -mtDNA (ccf-mtDNA), as well as blood, urine and muscle mtDNA heteroplasmy were evaluated. Patients also underwent a brain standardized MR protocol that included volumetric T1-weighted images and diffusion-weighted MRI. Twenty sex- and age-matched healthy controls were included. Voxel-wise analysis was performed on T1-weighted and diffusion imaging, respectively with VBM (voxel-based morphometry) and TBSS (Tract-based Spatial Statistics). Ventricular lactate was also evaluated by 1H-MR spectroscopy. RESULTS: A widespread cortical gray matter (GM) loss was observed, more severe (p < 0.001) in the bilateral calcarine, insular, frontal and parietal cortex, along with infratentorial cerebellar cortex. High urine mtDNA mutation load, high levels of plasma lactate and alanine, low levels of plasma arginine, high levels of serum FGF-21 and ventricular lactate accumulation significantly (p < 0.05) correlated with the reduced brain GM density. Widespread microstructural alterations were highlighted in the white matter, significantly (p < 0.05) correlated with plasma alanine and arginine levels, with mtDNA mutation load in urine, with high level of serum GDF-15 and with high content of plasma ccf-mtDNA. CONCLUSIONS: Our results suggest that the synergy of two pathogenic mechanisms, mtDNA-related mitochondrial respiratory deficiency and defective nitric oxide metabolism, contributes to the brain neurodegeneration in m.3243A > G patients.

Open Access Physical Therapy Journals: Do Predatory Journals Publish Lower-Quality Randomized Controlled Trials?

OBJECTIVES: To compare the quality of randomized controlled trials (RCTs) published in predatory and nonpredatory journals in the field of physical therapy. DATA SOURCES: From a list of 18 journals included either on Beall's list (n=9) or in the Directory of Open Access Journals (DOAJ) (n=9), 2 independent assessors extracted all the RCTs published between 2014 and 2017. When journals published more than 40 RCTs, a sample of 40 trials was randomly extracted, preserving the proportions among years. Indexing in PubMed, country of journal publication, and dates of submission or acceptance were also recorded for each journal. MAIN OUTCOME MEASURES: The PEDro (Physiotherapy Evidence Database) scale and duration of the peer review. RESULTS: Four hundred ten RCTs were included. The mean PEDro score of articles published in non-Beall, DOAJ journals was higher than those published in Beall journals (mean score ± SD, 5.8±1.7 vs 4.5±1.5; P<.001), with the differences increasing when the indexing in PubMed was also considered (6.5±1.5 vs 4.4±1.5; P<.001). The peer review duration was significantly longer in non-Beall than in Beall journals (mean duration [d] ± SD, 145.2±92.9 vs 45.4±38.8; P<.001) and in journals indexed in PubMed than in nonindexed journals (136.6±100.7 vs 60.4±55.7; P<.001). Indexing in PubMed was the strongest independent variable associated with the PEDro score (adjusted R2=0.182), but noninclusion on Beall's list explained an additional, albeit small, portion of the PEDro score variance (cumulative adjusted R2=0.214). CONCLUSIONS: Potentially predatory journals publish lower-quality trials and have a shorter peer review process than non-Beall journals included in the DOAJ database.

In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain metabolites at 3T.

PURPOSE: The transverse relaxation times T2 of 17 metabolites in vivo at 3T is reported and region specific differences are addressed. METHODS: An echo-time series protocol was applied to one, two, or three volumes of interest with different fraction of white and gray matter including a total number of 106 healthy volunteers and acquiring a total number of 128 spectra. The data were fitted with the 2D fitting tool ProFit2, which included individual line shape modeling for all metabolites and allowed the T2 calculation of 28 moieties of 17 metabolites. RESULTS: The T2 of 10 metabolites and their moieties have been reported for the first time. Region specific T2 differences in white and gray matter enriched tissue occur in 16 of 17 metabolites examined including single resonance lines and coupled spin systems. CONCLUSION: The relaxation time T2 is regions specific and has to be considered when applying tissue composition correction for internal water referencing. Magn Reson Med 80:452-461, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is the commonest autosomal recessive ataxia, caused by GAA triplet expansion in the frataxin gene. Neuropathological studies in FRDA demonstrate that besides the primary neurodegeneration of the dorsal root ganglia, there is a progressive atrophy of the cerebellar dentate nucleus. Diffusion-weighted imaging (DWI) detected microstructural alterations in the cerebellum of FRDA patients. To investigate the biochemical basis of these alterations, we used both DWI and proton MR spectroscopy (1H-MRS) to study the same cerebellar volume of interest (VOI) including the dentate nucleus. DWI and 1H-MRS study of the left cerebellar hemisphere was performed in 28 genetically proven FRDA patients and 35 healthy controls. In FRDA mean diffusivity (MD) values were calculated for the same 1H-MRS VOI. Clinical severity was evaluated using the International Cooperative Ataxia Rating Scale (ICARS). FRDA patients showed a significant reduction of N-acetyl-aspartate (NAA), a neuroaxonal marker, and choline (Cho), a membrane marker, both expressed relatively to creatine (Cr), and increased MD values. In FRDA patients NAA/Cr negatively correlated with MD values (r = -0.396, p = 0.037) and with ICARS score (r = -0.669, p < 0.001). Age-normalized NAA/Cr loss correlated with the GAA expansion (r = -0.492, p = 0.008). The reduced cerebellar NAA/Cr in FRDA suggests that neuroaxonal loss is related to the microstructural changes determining higher MD values. The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions.

Early experience with automatic pressure-controlled cerebrospinal fluid drainage during thoracic endovascular aortic repair.

PURPOSE: To report initial experience with automatic pressure-controlled cerebrospinal fluid drainage (CSFD) during thoracic endovascular aortic repair (TEVAR). METHODS: A prospective nonrandomized study enrolled 30 consecutive patients (median age 68 years, range 42-89; 18 men) who underwent TEVAR between March 2012 and July 2013 and were considered to be at high risk for postoperative spinal cord ischemia (SCI), fulfilling 2 of the following criteria: stent-graft length >20 cm, left subclavian artery coverage, and previous infrarenal aortic repair. All patients received perioperative CSFD via the LiquoGuard system. The protocol aimed for a CSF pressure of 10 mm Hg and duration of CSFD of 3 or 7 days in asymptomatic or symptomatic patients, respectively. Muscle strength of the lower extremities was assessed with the Oxford muscle strength grading scale. RESULTS: Completion of the CSFD protocol was achieved in 26 (87%) of 30 patients. CSFD was prematurely stopped due to catheter dislocation in 1 patient and bloody spinal fluid in 3 patients. CSFD was performed for a median of 3 days (range 1-7). Median total CSFD volume was 714 mL (range 13-2369), with a median 192 mL drained per 24 hours. The SCI rate was 3% (1/30). CSFD-related complications were observed in 33% of the patients: 1 fatal intracranial hemorrhage, 3 bloody spinal fluid episodes, 3 persistent CSF leaks requiring epidural blood patch, and 3 post lumbar puncture headaches. Mortality during a median follow-up of 16 months (range 10-25) was 3% (1/30). CONCLUSION: Prophylactic CSFD was associated with a low SCI rate in a high-risk patient collective undergoing TEVAR. Monitoring and drainage by an automatic modus was feasible, reproducible, and reliable but associated with relevant drainage-associated complications.

Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. METHODS: We included 29 mild-moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest-activity rhythm, chromatic pupillometry analyzed with a new data-fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. RESULTS: We demonstrated a significant thinning of the infero-temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian-impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil-light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. INTERPRETATION: Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

Electrochemical milling and faceting: size reduction and catalytic activation of palladium nanoparticles.

Improved performance through milling: A method for enhancing the catalytic activity of supported metal nanoparticles is reported. This method enhances the activity for the ethanol electro-oxidation of a supported palladium catalyst. The much higher catalytic performance is ascribed to the increased electrochemically active surface area as well as the generation of high-index facets at the milled nanoparticle surface.

Reliability of the PEDro scale: comparison between trials published in predatory and non-predatory journals.

BACKGROUND: Lack of effective peer-review process of predatory journals, resulting in more ambiguity in reporting, language and incomplete descriptions of processes might have an impact on the reliability of PEDro scale. The aim of this investigation was to compare the reliability of the PEDro scale when evaluating the methodological quality of RCTs published in predatory (PJs) and non-predatory (NPJs) journals, to more confidently select interventions appropriate for application to practice. METHODS: A selected sample of RCTs was independently rated by two raters randomly selected among 11 physical therapists. Reliability of each item of the PEDro scale and the total PEDro score were assessed by Cohen's kappa statistic and percent of agreement and by Intraclass Correlation Coefficients (ICC) and the Standard Error of Measurement (SEM), respectively. The Chi-square test was used to compare the rate of agreement between PJs and NPJs. RESULTS: A total number of 298 RCTs were assessed (119 published in NPJs). Cronbach's alphas were .704 and .845 for trials published in PJs and NPJs, respectively. Kappa values for individual scale items ranged from .14 to .73 for PJs and from .09 to .70 for NPJs. The ICC was .537 (95% CI .425-.634) and .729 (95% CI .632-.803), and SEM was 1.055 and 0.957 for PJs and NPJs, respectively. Inter-rater reliability in discriminating between studies of moderate to high and low quality was higher for NPJs (k = .57) than for PJs (k = .28). CONCLUSIONS: Interrater reliability of PEDro score of RCTs published in PJs is lower than that of trials published in NPJs, likely also due to ambiguous language and incomplete reporting. This might make the detection of risk of bias more difficult when selecting interventions appropriate for application to practice or producing secondary literature.

In Vivo Parieto-Occipital White Matter Metabolism Is Correlated with Visuospatial Deficits in Adult DM1 Patients.

Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a (CTG) expansion in the DM protein kinase (DMPK) gene, representing the most common adult muscular dystrophy, characterized by a multisystem involvement with predominantly skeletal muscle and brain affection. Neuroimaging studies showed widespread white matter changes and brain atrophy in DM1, but only a few studies investigated the role of white matter metabolism in the pathophysiology of central nervous system impairment. We aim to reveal the relationship between the metabolic profile of parieto-occipital white matter (POWM) as evaluated with proton MR spectroscopy technique, with the visuoperceptual and visuoconstructional dysfunctions in DM1 patients. MR spectroscopy (3 Tesla) and neuropsychological evaluations were performed in 34 DM1 patients (19 F, age: 46.4 ± 12.1 years, disease duration: 18.7 ± 11.6 years). The content of neuro-axonal marker N-acetyl-aspartate, both relative to Creatine (NAA/Cr) and to myo-Inositol (NAA/mI) resulted significantly lower in DM1 patients compared to HC (p-values < 0.0001). NAA/Cr and NAA/mI correlated with the copy of the Rey-Osterrieth complex figure (r = 0.366, p = 0.033; r = 0.401, p = 0.019, respectively) and with Street's completion tests scores (r = 0.409, p = 0.016; r = 0.341, p = 0.048 respectively). The proportion of white matter hyperintensities within the MR spectroscopy voxel did not correlate with the metabolite content. In this study, POWM metabolic alterations in DM1 patients were not associated with the white matter morphological changes and correlated with specific neuropsychological deficits.

In situ FTIR spectroelectrochemical study on the mechanism of ethylene glycol electrocatalytic oxidation at a Pd electrode.

The adsorption and electrooxidation pathways of ethylene glycol (EG) on polycrystalline palladium surfaces have been investigated in both alkaline and acidic media by in situ FTIR spectroscopy in conjunction with cyclic voltammetry. Palladium exhibits a high electrocatalytic activity in alkaline solution with low onset oxidation potentials and high current densities, depending on the pH, as well as on the supporting electrolyte. Higher potentials are required for EG oxidation in acidic solutions, where the catalytic performance decreases with increasing the pH. The products and intermediates of EG oxidation on Pd are influenced by the pH. In alkaline media, both C(2) species (glycolate, glyoxal, glyoxylate and oxalate) and C(1) species (formate and carbonate) are formed in mutual concentrations depending on the pH. In contrast, CO(2) is selectively produced in acidic aqueous solution.

Brain functional MRI responses to blue light stimulation in Leber's hereditary optic neuropathy.

Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive photoreceptors contributing both to image and non-image-forming (NIF) functions of the eye. They convey light signal to the brain to modulate circadian entrainment, sleep, alertness, cognition, brightness perception and coarse vision. Given that rods and cones also contribute to all these impacts of light, isolating mRGC visual and NIF roles in humans is challenging so that mRGC functions remains to be fully characterized. Here, we evaluated light-driven visual and cognitive brain responses in Leber's Hereditary Optic Neuropathy (LHON), an inherited optic neuropathy that is characterized by a selective relative sparing of the melanopsin-expressing retinal ganglion cells (mRGCs). Twelve patients and twelve matched healthy controls (HC) were enrolled in a functional brain magnetic resonance imaging (fMRI) protocol including visual and visual-cognitive paradigms under blue (480 nm) and red (620 nm) light exposures. Primary visual cortex activation was detected in LHON patients; in particular higher occipital activation was found in response to sustained blue vs. red stimulation in LHON vs. HC. Similarly, brain responses to the executive task were larger under blue vs. red light in LHON over lateral prefrontal cortex. These findings are in line with the relative mRGC sparing demonstrated in LHON and support the mRGC contribution to both non-visual and visual brain functions, with potential implication for visual rehabilitation in hereditary optic neuropathy patients.

Brain MRS correlates with mitochondrial dysfunction biomarkers in MELAS-associated mtDNA mutations.

OBJECTIVE: The purpose of this study was to investigate correlations between brain proton magnetic resonance spectroscopy (1 H-MRS) findings with serum biomarkers and heteroplasmy of mitochondrial DNA (mtDNA) mutations. This study enrolled patients carrying mtDNA mutations associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), and MELAS-Spectrum Syndrome (MSS). METHODS: Consecutive patients carrying mtDNA mutations associated with MELAS and MSS were recruited and their serum concentrations of lactate, alanine, and heteroplasmic mtDNA mutant load were evaluated. The brain protocol included single-voxel 1 H-MRS (1.5T) in the medial parieto-occipital cortex (MPOC), left cerebellar hemisphere, parieto-occipital white matter (POWM), and lateral ventricles. Relative metabolite concentrations of N-acetyl-aspartate (NAA), choline (Cho), and myo-inositol (mI) were estimated relative to creatine (Cr), using LCModel 6.3. RESULTS: Six patients with MELAS (age 28 ± 13 years, 3 [50%] female) and 17 with MSS (age 45 ± 11 years, 7 [41%] female) and 39 sex- and age-matched healthy controls (HC) were enrolled. These patients demonstrated a lower NAA/Cr ratio in MPOC compared to HC (p = 0.006), which inversely correlated with serum lactate (p = 0.021, rho = -0.68) and muscle mtDNA heteroplasmy (p < 0.001, rho = -0.80). Similarly, in the cerebellum patients had lower NAA/Cr (p < 0.001), Cho/Cr (p = 0.002), and NAA/mI (p = 0.001) ratios, which negatively correlated with mtDNA blood heteroplasmy (p = 0.001, rho = -0.81) and with alanine (p = 0.050, rho = -0.67). Ventricular lactate was present in 78.3% (18/23) of patients, correlating with serum lactate (p = 0.024, rho = 0.58). CONCLUSION: Correlations were found between the peripheral and biochemical markers of mitochondrial dysfunction and brain in vivo markers of neurodegeneration, supporting the use of both biomarkers as signatures of MELAS and MSS disease, to evaluate the efficacy of potential treatments.

Domino rhodium/palladium-catalyzed dehydrogenation reactions of alcohols to acids by hydrogen transfer to inactivated alkenes.

The combination of the d(8) Rh(I) diolefin amide [Rh(trop(2)N)(PPh(3))] (trop(2)N=bis(5-H-dibenzo[a,d]cyclohepten-5-yl)amide) and a palladium heterogeneous catalyst results in the formation of a superior catalyst system for the dehydrogenative coupling of alcohols. The overall process represents a mild and direct method for the synthesis of aromatic and heteroaromatic carboxylic acids for which inactivated olefins can be used as hydrogen acceptors. Allyl alcohols are also applicable to this coupling reaction and provide the corresponding saturated aliphatic carboxylic acids. This transformation has been found to be very efficient in the presence of silica-supported palladium nanoparticles. The dehydrogenation of benzyl alcohol by the rhodium amide, [Rh]N, follows the well established mechanism of metal-ligand bifunctional catalysis. The resulting amino hydride complex, [RhH]NH, transfers a H(2) molecule to the Pd nanoparticles, which, in turn, deliver hydrogen to the inactivated alkene. Thus a domino catalytic reaction is developed which promotes the reaction R-CH(2)-OH+NaOH+2 alkene-->R-COONa+2 alkane.

High-pressure investigations under CO/H2 of rhodium complexes containing hemispherical diphosphites.

The two rhodium complexes [Rh(acac)(L(R))] (L(R)=(S,S)-5,11,17,23-tetra-tert-butyl-25,27-di(OR)-26,28-bis(1,1'-binaphthyl-2,2'-dioxyphosphanyloxy)calix[4]arene; 6: R=benzyl, 7: R=fluorenyl), each based on a hemispherical chelator forming a pocket about the metal centre upon chelation, are active in the hydroformylation of 1-octene and styrene. As expected for this family of diphosphanes, both complexes resulted in remarkably high selectivity towards the linear aldehyde in the hydroformylation of 1-octene (l/b≈15 for both complexes). Linear aldehyde selectivity was also observed when using styrene, but surprisingly only 6 displayed a marked preference for the linear product (l/b=12.4 (6) vs. 1.9 (7)). A detailed study of the structure of the complexes under CO or CO/H(2) in toluene was performed by high-pressure NMR (HP NMR) and FT-IR (HP-IR) spectroscopies. The spectroscopic data revealed that treatment of 6 with CO gave [Rh(acac)(CO)(η(1)-L(benzyl))] (8), in which the diphosphite behaves as a unidentate ligand. Subsequent addition of H(2) to the solution resulted in a well-defined chelate complex with the formula [RhH(CO)(2)(L(benzyl))] (9). Unlike 6, treatment of complex 7 with CO only led to ligand dissociation and concomitant formation of [Rh(acac)(CO)(2)], but upon addition of H(2) a chelate complex analogous to 9 was formed quantitatively. In both [RhH(CO)(2)(L(R))] complexes the diphosphite adopts the bis-equatorial coordination mode, a structural feature known to favour the formation of linear aldehydes. As revealed by variable-temperature NMR spectroscopy, these complexes show the typical fluxionality of trigonal bipyramidal [RhH(CO)(2)(diphosphane)] complexes. The lower linear selectivity of 7 versus 6 in the hydroformylation of styrene was assigned to steric effects, due to the pocket in which the catalysis takes place being less adapted to accommodate CO or larger olefins and, therefore, possibly leading to facile ligand decoordination. This interpretation was corroborated by an X-ray structure determination carried out for 7.

Intramolecular sigma-bond metathesis/protonolysis on zirconium(IV) and hafnium(IV) pyridylamido olefin polymerization catalyst precursors: exploring unexpected reactivity paths.

A temperature-controlled metathesis/protonolysis takes place on group 4 amidopyridinate polymerization catalyst precursors. Unraveling this unprecedented reactivity path allowed us to highlight the importance of the metal precursor choice while preparing improved catalytic structures or studying new catalytic processes.

Author Correction: Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome.

Wolfram syndrome (WS) is a recessive multisystem disorder defined by the association of diabetes mellitus and optic atrophy, reminiscent of mitochondrial diseases. The role played by mitochondria remains elusive, with contradictory results on the occurrence of mitochondrial dysfunction. We evaluated 13 recessive WS patients by deep clinical phenotyping, including optical coherence tomography (OCT), serum lactic acid at rest and after standardized exercise, brain Magnetic Resonance Imaging, and brain and muscle Magnetic Resonance Spectroscopy (MRS). Finally, we investigated mitochondrial bioenergetics, network morphology, and calcium handling in patient-derived fibroblasts. Our results do not support a primary mitochondrial dysfunction in WS patients, as suggested by MRS studies, OCT pattern of retinal nerve fiber layer loss, and, in fibroblasts, by mitochondrial bioenergetics and network morphology results. However, we clearly found calcium mishandling between endoplasmic reticulum (ER) and mitochondria, which, under specific metabolic conditions of increased energy requirements and in selected tissue or cell types, may turn into a secondary mitochondrial dysfunction. Critically, we showed that Wolframin (WFS1) protein is enriched at mitochondrial-associated ER membranes and that in patient-derived fibroblasts WFS1 protein is completely absent. These findings support a loss-of-function pathogenic mechanism for missense mutations in WFS1, ultimately leading to defective calcium influx within mitochondria.

The endovascular treatment of juxta-renal abdominal aortic aneurysm using fenestrated endograft: early and mid-term results.

BACKGROUND: The aim of the present study was to evaluate the early and mid-term results of the endovascular treatment of juxta-renal abdominal aortic aneurysms (j-AAA) using fenestrated endograft (FEVAR). METHODS: Between 2008 to 2013 all consecutive patients underwent FEVAR using Cook-Zenith fenestrated endograft for treating j-AAA (proximal neck length <5 mm) with renal aortic α/ß angle <60°, were prospectively collected in a database. Cardiovascular risk factors, comorbidities, aortic-iliac morphological features, intra and post-procedural data were analyzed. Preoperative FEVAR planning was performed by a thoraco-abdominal computer tomography angiography (CTA) and the 3D/Center Lumen Line reconstructions (3mensio Medical Imaging, Bilthoven, The Netherlands). Follow-up was conducted by duplex ultrasound (DUS)/ contrast enhancement DUS (CEUS) and/or CTA at 1, 6, and 12 months, and yearly thereafter. Early endpoints were technical (TS) and clinical success (CS), renal function worsening (≥30% of preoperative creatinine value) and type I/III endoleak. Mid-term endpoints were: type I/III endoleak, target visceral vessels patency, j-AAA shrinkage, freedom from reintervention and survival. RESULTS: Twenty patients (94.7% of whom male; mean age: 73.4±5.9 years; ASA≥3: 100%) were enrolled. The mean neck length and j-AAA diameter were 2±1.4 mm (range: 0-4 mm) and 54.9±5 mm, respectively. Eleven (55%) endograft with two fenestrations and a scallop, 8 (45%) with three fenestrations and a scallop, and one (5%) with one fenestration and a scallop were implanted. Sixty-seven visceral vessels were re-vascularized. TS and CS were 100% and 95%, respectively (1/20 30-day mortality). Perioperative renal function worsening was observed in 15% of cases. The mean follow-up was 25±20 months (range: 2-72 months). No type I/III endoleak or occlusion of target visceral vessels occurred. There was j-AAA shrinkage in 65% of patients and no cases of j-AAA enlargement were observed. There were no FEVAR-related reinterventions. Survival at 12, 24, and 36 months were 89.4%, 80.5%, and 80.5%, respectively. CONCLUSIONS: According to our results, the endovascular treatment for j-AAA, with α/ß angle <60°, is safe and effective.