CO oxidation reactions on 3-d single metal atom catalysts/MgO(100).

The present work deals with a comprehensive computational theoretical study of the molecular CO and O2 adsorption on 3d single atoms (M/MgO(100)). The study is based on the chemical elements of the 3d row, as they represent an economic advantage compared with the so-called noble metals. The present study has been performed employing density functional theory calculations. Through the representation of the metastable states, we perform a synergetic analysis of the CO oxidation reaction to find trends that suggest the possible use of new candidates such as Ni/MgO(100) or Cu/MgO(100) single-atom catalysts, for this type of redox reaction. We found that Ni and Cu produce energetically viable CO to CO2 reactions. Ni and Cu atoms show the greatest diffusion barrier and are the best candidates due to their low sintering capability. The energetic and electronic properties of the single Cu and Ni atoms on MgO (100) give them the best characteristics to help in the CO oxidation process.

Developing and validating high-value patient digital follow-up services: a pilot study in cardiac surgery.

BACKGROUND: The existing digital healthcare solutions demand a service development approach that assesses needs, experience, and outcomes, to develop high-value digital healthcare services. The objective of this study was to develop a digital transformation of the patients' follow-up service after cardiac surgery, based on a remote patient monitoring service that would respond to the real context challenges. METHODS: The study followed the Design Science Research methodology framework and incorporated concepts from the Lean startup method to start designing a minimal viable product (MVP) from the available resources. The service was implemented in a pilot study with 29 patients in 4 iterative develop-test-learn cycles, with the engagement of developers, researchers, clinical teams, and patients. RESULTS: Patients reported outcomes daily for 30 days after surgery through Internet-of-Things (IoT) devices and a mobile app. The service's evaluation considered experience, feasibility, and effectiveness. It generated high satisfaction and high adherence among users, fewer readmissions, with an average of 7 ± 4.5 clinical actions per patient, primarily due to abnormal systolic blood pressure or wound-related issues. CONCLUSIONS: We propose a 6-step methodology to design and validate a high-value digital health care service based on collaborative learning, real-time development, iterative testing, and value assessment.

Colored cotton crop wastes valorization through pyrolysis: a study of energetic characterization and analytical Py-GC/MS.

The present work aimed to study different parts of colored cotton waste through energetic characterization and analytical flash pyrolysis. Stalks and bolls of BRS cotton cultivars from Sementes do Brasil (Green, Ruby, Topaz and Jade) were studied, using white cotton (BRS 286) as a comparison. The energetic potential of biomass was evaluated by bulk density, High Heating Value (HHV), proximate and ultimate analysis, compositional and thermogravimetric analysis (TGA). Pyrolysis was performed in a micro-pyrolyzer and the products were identified by gas chromatography and mass spectroscopy (Py-GC/MS). The results indicated a significant energetic potential, suggesting that can be used as an alternative energy source for thermochemical processes. The results of conventional pyrolysis indicated the presence of oxygenated compounds of different organic groups: aldehydes, ketones, phenols, furans and ethers, characteristic of the decomposition of lignocellulosic materials. Light organic acids in the C1-C4 range stood out the most, followed by phenols that appeared in a considerable proportion. Finally, it is concluded that the energy potential and pyrolysis products of the different parts (stalks and bolls) of colored cotton waste can be used to generate bioenergy and various chemical compounds of plant origin from green chemistry.

TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review.

BACKGROUND: Multiple mitochondrial DNA (mtDNA) deletions usually have a mendelian inheritance secondary to mutation in nuclear genes. One of these is the Twinkle gene whose mutation is responsible for autosomal dominant progressive external ophthalmoplegia (PEO). The number of reported cases with mainly myopathic symptoms and possible nervous system involvement related to Twinkle gene mutation is limited. We present a new French family of whom two members displayed myopathy and neuropathy associated with PEO, and we perform a clinical review in light of other observations reported in the literature. METHODS: The proband, one son and the daughter have been investigated. Southern blot analysis and long-range PCR assay have been performed from muscle biopsy specimens. Coding exons and flanking intron regions of polymerase gamma (POLG) and DNA helicase (Twinkle) genes were sequenced. RESULTS: Multiple mitochondrial DNA deletions have been found and sequencing of the Twinkle gene showed the change p.R374Q. CONCLUSION: Two other families from the literature also had the R374Q mutation. Symptoms reported in association with this mutation were myopathy, peripheral neuropathy, dysarthria and/or dysphagia, respiratory insufficiency and parkinsonism. Respiratory insufficiency caused by chest wall weakness was reported in other families with different Twinkle gene mutations, and one might provide exercise intolerance, dysarthria and/or dysphagia as symptoms in favor of the diagnosis. Occurrence of impressive emaciation was a peculiarity in our family.

Allelic origin of the abnormal prion protein isoform in familial prion diseases.

The hallmark of prion diseases is the presence of an aberrant isoform of the prion protein (PrP(res)) that is insoluble in nondenaturing detergents and resistant to proteases. We investigated the allelic origin of PrP(res) in brains of subjects heterozygous for the D178N mutation linked to fatal familial insomnia (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD178), as well as for insertional mutations associated with another CJD subtype. We found that in FFI and CJD178 subjects, only mutant PrP was detergent-insoluble and protease-resistant. Therefore, PrP(res) derives exclusively from the mutant allele carrying the D178N mutation. In contrast, in the CJD subtype harboring insertional mutations, wild-type PrP was also detergent-insoluble and likely to be protease-resistant. Our findings indicate that the participation of the wild-type PrP in the formation of PrP(res) depends on the type of mutations, providing an insight into the molecular mechanisms underlying the phenotypic heterogeneity in familial prion diseases.

Usefulness of combined nerve and muscle biopsy in the diagnosis of amyloid neuropathy--a study of 6 new cases.

OBJECTIVE: Most cases of familial amyloid polyneuropathy are identified by molecular genetic analysis of the transthyretin (TTR) gene. However, it is not uncommon to find unexpected amyloid deposits marked by the anti-TTR serum in the endoneurium of aged patients. Light chain amyloid deposits may also be found in the endoneurium. During these past 5 years, we studied the muscle and nerve biopsies from 6 patients which revealed amyloid deposits. There were 2 patients with an idiopathic polyneuropathy and 4 with monoclonal gammopathy (MG). METHODS: In each case, specimens from the superficial peroneal nerve and peroneus brevis muscle were taken by the same cutaneous incision. RESULTS: Amyloid deposits were visible in the endoneurium of 2 cases and only on muscle specimens in 3 other cases, 1 with a MG and 2 with an idiopathic polyneuropathy. Amyloid deposits were strongly stained with the anti-TTR serum in the muscle specimens of the 2 idiopathic cases, mainly located in vessel walls. In one patient with polyneuropathy and MG, a small endoneurial amyloid deposit surprisingly revealed to be immunostained by the anti-TTR serum. In another case, a small amyloid deposit in close relationship with a macrophage was only visible in the endoneurium by electron microscopy. COMMENTS: Amyloid deposits were only visible on muscle fragments in 3 cases and were strongly marked by the anti-TTR serum in 2 of them, indicating their familial origin. Combining muscle and nerve biopsy raises the number of cases with visible amyloid deposits.

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism.

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism.

Proteomic profile of histotroph during early embryo development in mares.

There is a complex cascade involving proteins during early embryo development and maternal recognition, which is very important for maintenance of a conceptus. The aim of this study was to compare proteomic profile of uterine fluid after ovulation in pregnant and cyclic mares. In the first cycle, samples of uterine fluid of 30 cyclic mares were collected on days 7 (n = 10), 10 (n = 10) and 13 (n = 10) post ovulation and constituted the Cyclic group. In the second cycle, the same mares were bred to a fertile stallion. At days 7, 10 and 13 uterine fluid samples were collected. Immediately after sample collection, the mare's uteri were flushed, and those with an embryo recovered were assigned to the Pregnant group. Of the 30 mares flushed embryos were recovered from 6 mares on day 7, 6 on day 10 and 6 on day 13. Samples from the mares without embryo recovery were excluded from both groups. The uterine fluid samples were processed by two-dimensional electrophoresis technique followed by matrix assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry for the identification of relevant protein spots. From a total of 677 detected spots 19 were identified, 13 more abundant in Pregnant group and 6 in Cyclic group. In summary, pregnant and cyclic mares showed proteins with different abundance. Identified proteins were related to the transport of lipids through the embryo capsule, uterine motility, ATP generation, maternal immunological tolerance, cell proliferation, differentiation, metabolism and angiogenesis. Changes in the proteomic profile of uterine fluid during early embryo development in mares were related with the conceptus presence, suggesting that these alterations may be important for conceptus development and maternal recognition of pregnancy.

Sarcoid neuropathy: clinico-pathological study of 4 new cases and review of the literature.

There are several reviews devoted to neurosarcoidosis and a few reports restricted to sarcoid neuropathy. Since 1989, we have investigated 4 new cases of sarcoid neuropathy, 1 with chronic sensory motor neuropathy (CSMN), another with painful neuropathy and 2 with atypical chronic inflammatory demyelinating polyneuropathy (CIDP). In each case, biopsy specimens from the superficial peroneal nerve and peroneus brevis muscle were taken by the same cutaneous incision and studied on paraffin sections, semi-thin sections and under electron microscope. We compared neuropathological findings from our 4 cases with those from 34 well-studied nerve biopsies previously reported in the literature, and which concerned 16 cases of CSMN, 13 cases ofmononeuropathy multiplex, 2 cases of painful neuropathy and three cases of CIDP. In all of these 38 cases of sarcoid neuropathy, the characteristic noncaseiting granulomas (NCG) were observed on the nerve in 11 cases, on the muscle alone in 5, on both muscle and nerve in 10, and in the nerve and another parenchyma in 4. In the 8 remaining cases, NCG were observed in another parenchyma, mainly lung or lymph nodes. Moreover, necrotizing vasculitis was present in nerve biopsies from 8 cases and microvasculitis without obvious necrosis in 2 others. Nerve fiber lesions, which are mainly axonal, are probably related to mechanical compression by NCG and/or to an ischemic process due to vasculitis. Cytokines and immune factors may also play a role, especially in certain cases with a clinical presentation of CIDP.

A case of mononeuropathy multiplex with type II cryoglobulinemia, necrotizing vasculitis and low grade B cell lymphoma.

OBJECTIVE: To elucidate the cause and mechanisms of nerve fiber lesions in a case of mononeuropathy multiplex (MNM). MATERIAL AND METHODS: A 65-year-old man had a MNM for 6 months and no previous history of peripheral nerve impairment was known. He underwent a muscle and nerve biopsy by the same skin incision on the right leg. RESULTS: Paraffin-embedded fragments from the superficial peroneal nerve and peroneous brevis muscle disclosed characteristic lesions of necrotizing vasculitis. Complement had low levels, but a search for cryoglobulinemia was negative. Two months later a purpura appeared in the lower limbs and a mixed Type II cryoglobulinemia was disclosed, whereas a search for hepatitis C virus (HCV) remained negative. Five months later the blood contained 8,600 lymphocytes/mm3 and a low grade B cell lymphoma was disclosed in the bone marrow. CONCLUSIONS: Although not having HCV infection, our patient had mixed Type II cryoglobulinemia, necrotizing vasculitis and B cell lymphoma. Each of these three abnormalities might be in part responsible for nerve fibers impairment, with acute axonal degeneration. Mixed cryoglobulinemia must be searched carefully in patients with vasculitic neuropathy.

Peripheral neuropathy after autologous blood stem cell transplantation for multiple myeloma.

We report a case of peripheral neuropathy occurring after autologous blood stem cell transplantation (ABSCT) for multiple myeloma. The patient, free of neurological symptoms, was transplanted in partial remission, and achieved a complete remission after transplantation. A severe peripheral, symmetric, distal sensori-motor polyneuropathy appeared at day 25 and worsened progressively until commencement of corticosteroid therapy. A peripheral nerve biopsy showed endoneurial cellular infiltrates which were predominantly composed of T cells identified by immunocytochemistry. Ultrastructural examination showed acute axonal damage. Electrophysiologic studies performed before and during the treatment were consistent with a severe axonal degeneration and showed a marked improvement, concomitant with the favorable clinical outcome. This is the first report of peripheral neuropathy after ABSCT.

Abnormal proliferation of intraergastoplasmic microfilaments in myelinated schwann cells: ultrastructural study of two cases.

We report the ultrastructural findings in superficial peroneal nerve biopsies in two patients, one with idiopathic sensory neuropathy and the other with the Guillain-Barré syndrome and Hodgkin's disease. In addition to demyelination, there was an intense proliferation of microfilaments within numerous vesicles of the endoplasmic reticulum of a great number of myelinated Schwann cells. This abnormality does not appear to have been previously reported in the literature. The mechanisms responsible for this finding are unknown.

Neuronal apoptosis in Creutzfeldt-Jakob disease.

Neuronal loss is a salient feature of prion diseases; however, its causes and mechanisms are unclear The possibility that it could occur through an apoptotic process has been postulated and is consistent with the lack of inflammation in prion disorders as supported by experimental studies. In order to test this hypothesis in humans, we examined samples of frontal and temporal cerebral cortex, striatum, thalamus, and cerebellum from 16 patients who died from Creutzfeldt-Jakob disease. They included 5 sporadic cases, 5 familial, 3 iatrogenic, and 3 cases with the new variant. These were compared with age and sex matched controls. Using in situ end labelling, we identified apoptotic neurons in all the cases of Creutzfeldt-Jakob disease. A single labelled neuron was found in the eldest control. Apoptotic neurons were mostly found in damaged regions and their presence and abundance seemed to correlate closely with neuronal loss. This supports the view that apoptosis of neurons is a feature of prion diseases and may contribute to the neuronal loss which is one of the main characteristics of these conditions. Neuronal apoptosis also correlated well with microglial activation, as demonstrated by the expression of major histocompatibility complex class II antigens, and axonal damage, as identified by beta-amyloid protein precursor immunostaining. In contrast, we found no obvious relationship between the topography and severity of neuronal apoptosis and the type, topography, and abundance of prion protein deposits as demonstrated by immunocytochemistry.

Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene.

Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1 +/- 1.1 months) or a prolonged (30.8 +/- 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mal seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.

Neuronal apoptosis in fatal familial insomnia.

The possibility that neuronal loss in prion diseases occurs through an apoptotic process has been postulated and is consistent with the lack of inflammation in these disorders. In order to test this hypothesis in FFI, in which neuronal loss is the predominant neuropathological feature, we examined samples of thalamus, basal ganglia, cerebral cortex, cerebellum and medulla from 10 subjects with FFI. All the patients had the characteristic 178 N mutation of the PrP gene. Eight subjects were homozygous methionine/methionine at codon 129 and 2 were heterozygous methionine/valine. Apoptotic neurons were identified by in situ end labelling in all the FFI cases and in none of the controls. They were mostly found in damaged regions and their presence and abundance seemed to correlate closely with the neuronal loss. They were particularly abundant in the thalamus and medullary olives. In heterozygous cases who had a longer disease duration and more widespread cerebral changes, apoptotic neurons were also found in the neocortex and striatum. The abundance of apoptotic neurons also correlated well with microglial activation as demonstrated by the expression of major histocompatibility complex class II antigens. PrPres immunostaining was almost invariably negative, consistent with previous data showing the lack of obvious correlation between neuronal loss and PrPres deposits in prion diseases.

Molecular anatomy of the development of the human substantia nigra.

A series of 15 fetal and perinatal human brains (from week 12 of fetal life to day 2 after birth) was studied in order to describe the anatomical and molecular correlates of the substantia nigra ontogeny. In situ hybridization, immunohistochemistry and binding studies were used to detect D2 dopamine receptor (D2R) mRNA, D2R binding sites, dopamine membrane transporter (DAT) mRNA, tyrosine hydroxylase (TH) protein D1 dopamine receptor (D1R) protein and D1R binding sites. Dopaminergic (DA) neurons of the substantia nigra were detected through TH immunoreactivity from week 12. At week 16, the substantia nigra was clearly delineated as a compact group of intermingled neurons and fibers. From week 19, groups of DA neurons were segregated from the pars reticulata. These groups have been divided into the substantia nigra pars compacta, the ventral tegmental area and the retrorubral area. The DA neurons exhibited a gradual increase in size and branching development until birth. From week 12 onward they expressed several other markers of dopamine transmission, i.e., D2R mRNA, D2R binding sites and DAT mRNA. The ventral tegmental area expressed lower levels of mRNA for DAT and D2R than the pars compacta. From week 12, D1R immunoreactivity and D1R binding sites were also present in the substantia nigra pars reticulata. This suggests that projecting striatonigral neurons, known to express the D1R gene, have developed pathways connecting with the substantia nigra by week 12. Our results demonstrate that the developing substantia nigra in human displays early transcriptional and translational activity for the main constituents of dopaminergic transmission from week 12 and receives at this time dopaminoceptive inputs bearing D1 receptors from the striatum.

Ontogeny of the striatal neurons expressing the D1 dopamine receptor in humans.

We studied D1 dopamine receptor (D1R) gene expression in the human striatum during ontogeny by in situ hybridization, immunohistochemistry, and D1R ligand autoradiography. D1R mRNA, protein, and binding sites ([3H]SCH 23390) were detected in the striatum from week 12 of fetal life. At this time, D1R mRNA was predominant in the striosomal neurons; D1R immunoreactivity (D1R-IR) and D1R binding sites displayed a pattern similar to D1R mRNA. D1R-IR was essentially present in striosomal cell bodies and neuropil, whereas only a few cell bodies were detected in the matrix. From week 20 of fetal life, D1R gene expression developed in the matrix neurons as well, thus leading to an even D1R mRNA expression throughout striosomes and matrix compartments at birth. Comparative analysis of the expression of D1R and dynorphin mRNA show the same developmental patchy pattern up to week 26. Indeed, neurons expressing the D1R gene contain dynorphin mRNA; in contrast, they do not express the preproenkephalin A gene. At birth, the pattern of D1R mRNA expression level was sharply different from that of dynorphin (DYN) gene expression. High DYN mRNA expression was restricted to the striosomes, whereas high D1R mRNA expression was present in the whole striatum. These results demonstrate that, during human ontogeny, functional D1 receptors are expressed as early as week 12 in the striatum, developing initially in the striosomal neurons containing high dynorphin mRNA content. Toward the end of fetal life, there is a dissociation between D1R and DYN expression levels, suggesting that neuroanatomical or neurochemical modifications occur at this period, which may contribute to the regulation of the tone of the striatal D1R and DYN gene with topological specificity.