Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient.

BACKGROUND: Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome. CASE PRESENTATION: A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions. CONCLUSIONS: This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.

Relativistic DFT Probe for Reaction Energies and Electronic/Bonding Properties of Polypyrrolic Hetero-Bimetallic Actinide Complexes: Effects of Uranyl endo-Oxo Functionalization.

A series of hetero-bimetallic actinide complexes of the Schiff-base polypyrrolic macrocycle (L), featuring cation-cation interactions (CCIs), were systematically investigated using relativistic density functional theory (DFT). The tetrahydrofuran (THF) solvated complex [(THF)(OUVIOUIV)(THF)(L)]2+ has high reaction free energy (ΔrG), and its replacement with electron-donating iodine promotes the reaction thermodynamics to obtain uranyl iodide [(I)(OUVIOUIV)(I)(L)]2+ (UVI-UIV). Retaining this coordination geometry, calculations have been extended to other An(IV) (An = Th, Pa, Np, Pu), i.e., for the substitution of U(IV) to obtain UVI-AnIV. As a consequence, the reaction free energy is appreciably lowered, suggesting the thermodynamic feasibility for the experimental synthesis of these bimetallic complexes. Among all UVI-AnIV, the electron-spin density and high-lying occupied orbitals of UVI-PaIV show a large extent of electron transfer from electron-rich Pa(IV) to electron-deficient U(VI), leading to a more stable UV-PaV oxidation state. Additionally, the shortest bond distance and the comparatively negative Eint of the Pa-Oendo bond suggest more positive and negative charges (Q) of Pa and endo-oxo atoms, respectively. As a result of the enhanced Pa-Oendo bond and strong CCI in UVI-PaIV along with the corresponding lowest reaction free energy among all of the optimized complexes, uranyl species is a better candidate for the experimental synthesis in the ultimate context of environmental remediation.

Main-Group Metals Stabilized Polypyrrolic Uranyl(V) Complexes via Cation-Cation Interaction with the Uranyl exo-Oxo Atom: A Relativistic Density Functional Theory Study.

To explore the innovative uranyl(V) complexes by deeply understanding their coordination stability, relativistic density functional theory calculations have been performed to investigate the experimentally reported [(py)(R2AlOUVO)(py)(H2L)] [R = Me (1), iBu (2)] and [{(py)3MOUVO}(py)(H2L)] [M = Li (3), Na (4), K (5)] and their uranyl(VI) counterparts. Structural and topological analyses along with transformation-reaction energies and redox potentials were systematically studied. Geometrical and quantum theory of atoms in molecules analyses implied a linear U-Oexo-M feature in 1-3 and a bent one in 4 and 5. The calculated free energies (ΔrG) of reactions transforming 1/2 into 3/4/5 confirmed a higher stability of the latter ones, which were further corroborated by their reduction potentials (E0). The E0 value of 5 versus uranyl(VI) is close to its experimental value, particularly in solvation with spin-orbit coupling. The highest occupied and lowest unoccupied molecular orbitals of uranyl(V) and uranyl(VI) have predominant U(5fδ) character. Compared to mononuclear uranyl(VI), the coordination of aluminum and alkali metals to uranyl exo-oxo significantly contributes to the stabilization of uranyl(V) by altering the E0 value from -1.59 to -0.85, -0.91, -1.33, -1.50, and -1.46 V, respectively. The calculation results show a more positive E0 than that of the precursor 6VI/6 without exo-oxo coordination. The calculated E0 values of 3-5 are certainly more negative than those of 1 and 2. The alkali metals were found to activate U═O bonds more easily/readily than aluminum by coordination to the exo-oxo atom. In brief, the uranyl exo-oxo cation-cation-interaction enhanced the reduction ability from its uranyl(VI) analogue and raised the stability of the UV center.

Repair mechanism of astrocytes and non-astrocytes in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a destructive disease that incurs huge personal and social costs, and there is no effective treatment. Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus, the pathogenesis of SCI is still under investigation. AIM: To determine the key genes based on the modularization of in-depth analysis, in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI. METHODS: Firstly, the differences between injured and non-injured spinal cord of astrocyte (HA), injured and non-injured spinal cord of non-astrocyte (FLOW), injured spinal cord of non-injured astrocyte (HA) and non-injured spinal cord of non-astrocyte (FLOW), and non-injured spinal cord of astrocyte (HA) and non-astrocyte (FLOW) were analyzed. The total number of differentially expressed genes was obtained by merging the four groups of differential results. Secondly, the genes were co-expressed and clustered. Then, the enrichment of GO function and KEGG pathway of module genes was analyzed. Finally, non-coding RNA, transcription factors and drugs that regulate module genes were predicted using hypergeometric tests. RESULTS: In summary, we obtained 19 expression modules involving 5216 differentially expressed genes. Among them, miR-494, XIST and other genes were differentially expressed in SCI patients, and played an active regulatory role in dysfunction module, and these genes were recognized as the driving genes of SCI. Enrichment results showed that module genes were significantly involved in the biological processes of inflammation, oxidation and apoptosis. Signal pathways such as NF-kappa B/A20, AMPK and MAPK were significantly regulated. In addition, non-coding RNA pivot (including miR-136-5p and let-7d-5p, etc.) and transcription factor pivot (including NFKB1, MYC, etc.) were identified as significant regulatory dysfunction modules. CONCLUSION: Overall, this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI. These findings helped to reveal the core dysfunction modules, potential regulatory factors and driving genes of the disease, and to improve our understanding of its pathogenesis.

A relativistic DFT probe of polypyrrolic macrocyclic diuranium(III) complexes with terminal solvents and iodines.

Relativistic density functional theory finds that two isomers of a diuranium(III) complex of a polypyrrolic macrocycle (H4L) feature active sites on uranium moieties, allowing for their potential application in activating industrially and economically important small molecules. To address this, a series of adducts [(X)nU2(L)]((2-m)+) (X = THF, I(-) and HI; n = 1 and 2; m = 0, 1 and 2) have been examined. The coordination from X to the exposed uranium(s) changes the general geometry and electronic structure slightly. Thermodynamic calculations reveal that iodine termination is energetically favored over THF/HI coordination. Graphical abstract Scalar and spin-orbit coupling relativistic DFT calculation reveals that the active sites on the uranium moieties of [U2(L)](2+) lead to formation of adducts [(THF)nU2(L)](2+), [InU2(L)]((2-n)+) and [(HI)nU2(L)](2+) (n = 1 and 2). Coordination to the exposed uranium(s) changes geometrical and electronic properties slightly, but iodine termination is the most energetically favored.

Relativistic DFT and experimental studies of mono- and bis-actinyl complexes of an expanded Schiff-base polypyrrole macrocycle.

The computationally- and experimentally-determined molecular structures of a bis-uranyl(vi) complex of an expanded Schiff-base polypyrrolic macrocycle [(UO2)2(L)] are in close agreement only if the pyridine in the fifth equatorial donor site on the uranium is included in the calculations. The relativistic density functional theory (DFT) calculations presented here are augmented from those on previously reported simpler frameworks, and demonstrate that other augmentations, such as the incorporation of condensed-phase media and the changes in the peripheral groups of the ligand, have only a slight effect. Synthetic routes to pure samples of the bis- and mono-uranyl(vi) complexes have been developed using pyridine and arene solvents, respectively, allowing the experimental determination of the molecular structures by X-ray single crystal diffraction; these agree well with the calculated structures. A comprehensive set of calculations has been performed on a series of actinyl AnO2n+ complexes of this macrocyclic ligand. These include both bis- and mono-actinyl adducts for the metals U, Np and Pu, and formal oxidation states VI and V. The reduction potentials of the complexes for U, Np, and Pu, incorporating both solvation and spin-orbit coupling considerations, show the order Np > Pu > U. The agreement between experimental and computed data for U is excellent, suggesting that at this level of computation predictions made about the significantly more radiotoxic Np and Pu molecules should be accurate. A particularly unusual structure of the mononuclear plutonyl(v) complex was predicted by quantum chemical calculations, in which a twist in the macrocycle allows one of the two endo-oxo groups to form a hydrogen bond to one pyrrole group of the opposite side of the macrocycle, in accordance with this member of the set containing the most Lewis basic oxo groups.

Spinal Cord Kinking in Thoracic Myelopathy Caused by Ossification of the Ligamentum Flavum.

BACKGROUND: Ossification of the ligamentum flavum (OLF) is being increasingly recognized as a cause of thoracic myelopathy. This study was to describe a rare clinical entity of spinal cord kinking (SK) in thoracic myelopathy secondary to OLF. METHODS: The data of 95 patients with thoracic myelopathy secondary to OLF were analyzed retrospectively. The incidence and location of SK were determined using preoperative magnetic resonance imaging (MRI). The clinical presentation and radiological characteristics in patients with SK were analyzed. Posterior en bloc laminectomy with OLF was performed, and the surgical results were evaluated. RESULTS: SK was found in seven patients (7.4%) based on preoperative MRI. The patients included one male and six females with an average age of 55.6 years (range, 48-64 years). Five patients presented with radiculomyelopathy and two presented with typical thoracic myelopathy of spastic paraparesis. In all cases, the kinking was located just above the end of the spinal cord where the conus medullaris (CM) was compressed by the OLF. The degree of SK varied from mild to severe. The tip of the CM was located between the upper third of T11 to the lower third of L1, above the lower edge of L1. With an average follow-up of 30.4 months, the modified Japanese Orthopedic Association score significantly improved from 5.7 ± 1.8 preoperatively to 8.9 ± 1.4 postoperatively (t = 12.05; P < 0.0001) with an improvement rate of 63.1 ± 12.3%. CONCLUSIONS: SK is a rare radiological phenomenon. It is typically located at the thoracolumbar junction, where the CM is compressed by the OLF. Our findings indicate that these patients may benefit from a posterior decompressive procedure.

Highly valence-diversified binuclear uranium complexes of a schiff-base polypyrrolic macrocycle: prediction of unusual structures, electronic properties, and formation reactions.

On the basis of relativistic density functional theory calculations, homo- and heterovalent binuclear uranium complexes of a polypyrrolic macrocycle in a U-O-U bridging fashion have been investigated. These complexes show a variety of oxidation states for uranium ranging from III to VI, which have been confirmed by the calculated electron-spin density on each metal center. An equatorially 5-fold uranyl coordination mode is suitable for hexavalent uranium complexes, while silylation of the uranyl oxo is favored by pentavalent uranium. Uranyl oxo ligands are not required anymore for the coordination environment of tetra- and trivalent uranium because of their replacement by strong donors such as tetrahydrofuran and iodine. Optimization of binuclear U(VI)-U(III) complexes with various coordinating modes of U(III), donor numbers, and donor types reveals that 0.5-1.0 electron has been transferred from U(III) to U(VI). Consequently, U(V)-U(IV) complexes are more favorable. Electronic structures and formation reactions of several representative uranium complexes were calculated. For example, a 5f-based σ(U-U) bonding orbital is found in the diuranium(IV) complex, rationalizing the fact that it shows the shortest U-U distance (3.82 Å) among the studied binuclear complexes.

Poly[[aqua-(µ(5)-1H-benzimidazole-5,6-dicarboxyl-ato)(µ(4)-1H-benzimidazole-5,6-dicarboxyl-ato)dibarium] 4.5-hydrate].

The polymeric title compound, {[Ba(2)(C(9)H(4)N(2)O(4))(2)(H(2)O)]·4.5H(2)O}(n), adopts a layer structure parallel to (001) in which adjacent Ba(II) atoms are connected by two benzimidazole-5,6-dicarboxyl-ate dianions, one functioning in a µ(4)-bridging mode and the other in a µ(5)-bridging mode. The Ba atom having water in its coordination environment as well as the Ba atom without water exist in a nine-coordinate polyhedron of O atoms; the geometry is difficult to derive. Lattice water mol-ecules occupy the space between layers and inter-act with the layers through O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds. ne of the five lattice water molecules is equally disordered around an inversion centre and shows half-occupancy.

[Experimental study of biocompatibility of LIFEs in peripheral fascicles].

OBJECTIVE: To study the biocompatibility of longitudinally implanted intrafascicular electrodes (LIFEs) in a rabbit sciatic nerve model. And to discuss the possibility of peripheral fascicular signals as a new signal source to control an electronic prosthetic hand. METHODS: LIFEs were implanted chronically into sciatic peripheral fascicles of rabbits as recording and stimulating electrodes. Motor-evoked potentials (MEP) and cortical somatosensory-evoked potentials (CSEP) were recorded by using a transcranial stimulation system (TCS) over six-month period to observe the change of the signals recorded. At the end of the experiments, the fascicles at the electrodes implanted site were anatomized for histological examination under light microscope and transmission electron microscope. In human test, LIFEs were implanted into radial nerve, ulnar nerve and medial nerve of an amputee volunteer. Signals were detected when the volunteer was asked to do different movements of his missing hand, and the signals recorded by LIFEs were used to control an electronic prosthetic hand. RESULTS: The difference of onset latency (OL) of MEP and CSEP recorded at different time has remarkable statistical significance (one way ANOVA, P < 0.001). After multiple comparisons, onset latency (OL) of MEP and CSEP had no obvious change during 1 month, but significantly increased in the later time, and then became stable after 3 months after implantation. The difference of the interpeak amplitudes (IPAs) of MEP recorded at different time has remarkable statistical significance (one way ANOVA, P < 0.001). The interpeak amplitudes (IPAs) of MEP had no distinct change during 1 month, but significantly decreased over the next period, and then became stable after 3 months. Though the interpeak amplitudes (IPAs) of CSEP decreased slowly over six-month period of the study, the difference has no statistic significance (one way ANOVA, P > 0.05). At the end of experiment, histological examination indicated that a typical foreign body reaction developed and electrodes caused a mild damage to fascicles. But inflammatory cells and neuroma were not seen around the electrodes. Signals recorded by LIFEs planted in proximal radial, ulnar and median nerve of the amputated arm were different when the amputee volunteer was ordered to do some different movements with his mind. Some signals could be used to control the seven-freedom electronic prosthetic hand. CONCLUSIONS: Longitudinally implanted intrafascicular electrodes (LIFEs) have excellent biocompatibility with peripheral fascicles. They can be implanted chronically into fascicles and record signals. Furthermore, LIFEs can record physiological signals of peripheral fasciculi when hand moves, and these signals could be used to control an electronic prosthetic hand through further research.