Objective
To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.
...Methods
One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the United States. Seventy‐four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests.
Results
At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years. Within 4 years of follow‐up, 25 of 74 subjects (34%) developed dementia with Lewy bodies (n = 13), Parkinson disease (n = 6), or multiple system atrophy (n = 6). The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1). Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute. Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness. The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell.
Interpretation
Patients presenting with pure autonomic failure are at high risk of phenoconverting to a manifest CNS synucleinopathy. Specific clinical features predict future diagnosis. Ann Neurol 2017;81:287–297
Pure red cell aplasia (PRCA) is a rare anemia characterised by profound reticulocytopenia caused by a marked reduction in bone marrow erythroblasts, without abnormalities in other blood lineages. ...Blackfan-Diamond anemia is an inherited ribosomopathy responsible for a hereditary form of PRCA. Acquired PRCA are separated in primary and secondary forms, including Parvovirus B19 infection, thymoma, lymphoproliferative disorders, autoimmune diseases (lupus) and drug-induced PRCA. The pathophysiology of PRCA is not fully understood and involves both humoral and T lymphocyte autoreactive cells. In Parvovirus B19-related PRCA, treatment is based on polyvalent immunoglobulins. Thymectomy for thymoma is mandatory but results in prolonged remission in a limited number of cases. The therapeutic strategy is based on expert opinion: corticosteroids in monotherapy provide few sustained responses. The choice of an additional immunosuppressant drug is guided by the presence of an underlying disease. In most cases, cyclosporine A is the first choice providing the best response rate but requires a concentration monitoring (150 to 250 ng/mL). The second choice is cyclophosphamide in large granular lymphocyte leukaemia. Sirolimus (mTOR inhibitor) seems to be a promising option especially in refractory cases. Transfusion independence is the main objective. If the patient receives numerous red blood cell transfusions (> 20 packs), iron overload assessment is crucial to initiate an iron chelation. A retrospective and prospective national cohort (EPIC-F) has been set up and is now available to include each case of PRCA to improve the knowledge of this disease and to optimize the therapeutic strategy.
Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic clonal plasma cell or lymphoplasmacytic proliferative disorder. Recently, some case reports have described the ...association of pure red cell aplasia (PRCA) with MGUS, even with a relatively low monoclonal immunoglobulin burden. T large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by clonal expansion of T large granular lymphocytes, which is rare in China. There are some reports about T-LGL leukemia in patients with B-cell lymphoma; however, it is very rare that T-LGLL coexists with MGUS and clonal B-cell lymphoproliferative disorders (CB-LPD).
A 77-year-old man was hospitalized because of anemia. He was diagnosed with MGUS, CB-LPD, and PRCA. During the development of the disease, a group of abnormal T lymphocytes was detected by flow cytometry of peripheral blood.
Combining clinical manifestations with the result of T cell receptor gene rearrangement and immunophenotype, it was consistent with the diagnosis of T large granular lymphocyte leukemia.
The patient was treat with bortezomib and dexamethasone regimen, Rituximab and sirolimus.
The patient was transfusion independent after therapies.
We report a patient with 4 concomitant hematological disorders: T-LGLL, MGUS, CB-LPD, and PRCA, aiming to represent the clinical and flow cytometry characteristics of these concomitant diseases, analyze the mechanism between diseases, and provide a clinical reference.
A prerequisite for commercializing perovskite photovoltaics is to develop a swift and eco‐friendly synthesis route, which guarantees the mass production of halide perovskites in the industry. Herein, ...a green‐solvent‐assisted mechanochemical strategy is developed for fast synthesizing a stoichiometric δ‐phase formamidinium lead iodide (δ‐FAPbI3) powder, which serves as a high‐purity precursor for perovskite film deposition with low defects. The presynthesized δ‐FAPbI3 precursor possesses high concentration of micrometer‐sized colloids, which are in favor of preferable crystallization by spontaneous nucleation. The resultant perovskite films own preferred crystal orientations of cubic (100) plane, which is beneficial for superior carrier transport compared to that of the films with isotropic crystal orientations using “mixture of PbI2 and FAI” as precursors. As a result, high‐performance perovskite solar cells with a maximum power conversion efficiency of 24.2% are obtained. Moreover, the δ‐FAPbI3 powder shows superior storage stability for more than 10 months in ambient environment (40 ± 10% relative humidity), being conducive to a facile and practical storage for further commercialization.
A mechanochemical route to prepare stoichiometric‐pure and air‐stable δ‐FAPbI3 powders is developed, which can be stored for more than 10 months in ambient environment. Redissolving the δ‐FAPbI3 powders can generate a high concentration of large‐sized polyiodide colloids, which can serve as nuclei to promote heterogeneous nucleation for perovskite films. As a result, a competitive solar cell efficiency of 24.22% is achieved.
Primary progress has been made in the last 2 years, particularly in finding novel disease-causing genes for a number of autoinflammatory diseases and primary immunodeficiencies. Whole-exome ...sequencing has dramatically increased the pace at which causative genes are being discovered. CECR1 (Cat eye syndrome chromosome region, candidate 1) gene encodes adenosine deaminase 2 (ADA2) protein. Patients who carry CECR1 mutation(s) suffer from deficiency of ADA2 (DADA2). Here, we describe a patient with pure red cell aplasia discovered to have DADA2. We also review the literature on DADA2. This report will help raise awareness of physicians for this complex disease.
The first systematic study of linear and non-linear optical, magneto-optical and structural properties of pure TeO2 glass is presented with regard to different synthesis and material processing ...conditions. Prepared glasses were synthesized by the intermittent quenching from 900 ∘C in platinum or alumina crucibles and characterized prior to and after optical polishing. The position of the long-wavelength/phonon absorption edge was investigated using various optical models and experimentally obtained data of refractive index and Verdet constants were used for the estimation of magneto-optical anomaly parameter. During synthesis in alumina crucible, up to about 11 wt.% of Al2O3 incorporates into the glass (verified by EDS/XRF and Raman/FTIR spectroscopy) partially transforming the original pure TeO2 glass backbone structure composed of TeO4 trigonal bipyramids to TeO3+1 and TeO3 structural units with the expected integration of Al into Te−O−Al bridges. The presence of Al2O3 results in lowered density ρ (5.60 → 4.72 g cm−3), refractive index n1550 (2.086 → 1.927) and Verdet constant V632 (36.3 → 21.9 rad T−1 m−1) and in increased optical-band-gap energy Eg (3.69 → 3.72 eV) and Abbe number νD (19.9 → 26.9) compared to pure TeO2 glass prepared in platinum crucible. A dataset of the obtained complex optical parameters (refractive index and extinction coefficient) in the wide spectral range of 193 − 11000 nm is included in the supplementary part.
•Pure TeO2 glass: First complex study of optical and magneto-optical properties.•Impact of synthesis in alumina and Pt crucible on resulting glass properties.•Effect of polishing-induced modifications on optical properties.•Optical (n, k) and magneto-optical (V) constants determined in a broad spectral region.•Estimation of band-gap-energy Eg, magneto-optical anomaly (γ) and long-wavelength/phonon edge.
The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously ...reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence CI, -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure.
Zhiyi was one of the greatest Chinese Buddhist masters of his time. Pure Land greatly influenced his thoughts during his lifetime. This article examines Pure Land thought's influence on him from ...several perspectives. Firstly, Zhiyi's annotations on Pure Land scriptures, such as the Foshuo Amituo jing 佛說阿彌陀經 Skt. Amitābha Sūtra) and Guan Wulingshou jing 觀無量壽經 Skt. Amitāyur Dhyāna Sūtra; Contemplation Sūtra, demonstrate his understanding of the teachings. Secondly, Zhiyi stressed the importance of incorporating Pure Land thought into Tiantai 天台 practice. Thirdly, Zhiyi included elements associated with the Western Pure Land in his meditation practice. Lastly, Zhiyi said in his dying statement that he wanted to be reborn in Amitābha's Pure Land. In this wish, he expresses his conviction that the Pure Land teaching is the ultimate goal of a Buddhist. Therefore, it is evident that Zhiyi's religious beliefs, meditation and final destination in life were profoundly influenced by Pure Land thought.
Pure red cell aplasia (PRCA) is a rare hematological disorder with multiple etiologies. The multifaceted nature of this disease is emphasized by the variety of concomitant clinical features. Classic ...idiopathic presentation aside, prompt recognition of pathogenetic clues is important because of their diagnostic and therapeutic implications. As a consequence, treatment of PRCA is diverse and strictly dependent on the presented clinical scenario. Here, we propose a series of clinical vignettes that showcase instructive representative situations derived from our routine clinical practice. Using these illustrative clinical cases, we review the diagnostic workup needed for a precise diagnosis and the currently available therapeutic options, discussing their applications in regard to the various PRCA-associated conditions and individual patients' characteristics. Finally, we propose a treatment algorithm that may offer guidance for personalized therapeutic recommendations.
The presence of polyvinyl fluoride (PVDF) between electrode particles is a potentially critical factor to reduce the leaching rate of the electrode materials in spent lithium-ion batteries (LIBs). ...Pyrolysis method was proposed to remove the PVDF to improve the leaching behavior. The pyrolysis characteristics of electrode materials, PVDF and pure LiCoO2 were analyzed to determine the pyrolysis temperature. The content of functional groups representing PVDF in the pyrolyzed and un-pyrolyzed electrode material was measured by XPS to evaluate the pyrolysis effect. Subsequently, eco-friendly citric acid and ascorbic acid was used to leach pyrolyzed and un-pyrolyzed electrode materials. Meanwhile, leaching behavior of pure LiCoO2 was also verified to evaluate the leaching effect of waste LiCoO2, the leaching behavior of pyrolyzed and un-pyrolyzed electrode materials was analyzed to evaluate the enhancement effect of pyrolysis. The morphology of the leaching residue was analyzed by SEM to verify the leaching effect. Results show that pyrolysis at 500 °C can fully remove PVDF and enhance the leaching rate of electrode materials. Further, citric acid and ascorbic acid can achieve efficient and green leaching of electrode materials. The leaching rate of Li and Co in un-pyrolyzed electrode materials is 58.51 % and 58.88 %, while it is 92.01 % and 90.87 % in the pyrolyzed electrode materials. The XPS analysis of pyrolyzed electrode materials and SEM analysis of the leaching residue also verified that the pyrolysis achieved full removal of PVDF.
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