The Cellular and Humoral Immune Response to SARS-CoV-2 Messenger RNA Vaccines Is Significantly Better in Liver Transplant Patients Compared with Kidney Transplant Patients.

Patients after organ transplantation have impaired immune response after vaccination against the SARS-CoV-2 virus. So far, published studies have reported quite different response rates to SARS-CoV-2 vaccination, ranging from 15-79% in liver and kidney transplant recipients. Up to one year after the first vaccine dose, we analyzed the humoral and cellular immune response of 21 liver transplant (LTX) patients after vaccination with mRNA vaccines compared with 28 kidney transplant (KTX) patients. We evaluated IgG against the SARS-CoV-2 spike protein as well as SARS-CoV-2 specific T cells using an ELISpot assay that detected IFN-γ- and/or IL-2-expressing T cells. We found a cellular and/or humoral immune response in 100% of the LTX patients compared with 68% of the KTX patients. Antibody titers against the spike protein of SARS-CoV-2 were significantly higher in the LTX group, and significantly more LTX patients had detectable specific IL-2-producing T cells. The immunosuppression applied in our LTX cohort was lower compared with the KTX cohort (14% triple therapy in LTX patients vs. 79% in KTX patients). One year after the first vaccination, breakthrough infections could be detected in 41% of all organ transplant patients. None of those patients suffered from a severe course of COVID-19 disease, indicating that a partial vaccination response seemed to offer protection to immunosuppressed patients. The better immune response of LTX patients after SARS-CoV-2 vaccination might be due to less intense immunosuppressive therapy compared with KTX patients.

Feedback Signal from Motoneurons Influences a Rhythmic Pattern Generator.

Motoneurons are not mere output units of neuronal circuits that control motor behavior but participate in pattern generation. Research on the circuit that controls the crawling motor behavior in leeches indicated that motoneurons participate as modulators of this rhythmic motor pattern. Crawling results from successive bouts of elongation and contraction of the whole leech body. In the isolated segmental ganglia, dopamine can induce a rhythmic antiphasic activity of the motoneurons that control contraction (DE-3 motoneurons) and elongation (CV motoneurons). The study was performed in isolated ganglia where manipulation of the activity of specific motoneurons was performed in the course of fictive crawling (crawling). In this study, the membrane potential of CV was manipulated while crawling was monitored through the rhythmic activity of DE-3. Matching behavioral observations that show that elongation dominates the rhythmic pattern, the electrophysiological activity of CV motoneurons dominates the cycle. Brief excitation of CV motoneurons during crawling episodes resets the rhythmic activity of DE-3, indicating that CV feeds back to the rhythmic pattern generator. CV hyperpolarization accelerated the rhythm to an extent that depended on the magnitude of the cycle period, suggesting that CV exerted a positive feedback on the unit(s) of the pattern generator that controls the elongation phase. A simple computational model was implemented to test the consequences of such feedback. The simulations indicate that the duty cycle of CV depended on the strength of the positive feedback between CV and the pattern generator circuit.SIGNIFICANCE STATEMENT Rhythmic movements of animals are controlled by neuronal networks that have been conceived as hierarchical structures. At the basis of this hierarchy, we find the motoneurons, few neurons at the top control global aspects of the behavior (e.g., onset, duration); and within these two ends, specific neuronal circuits control the actual rhythmic pattern of movements. We have investigated whether motoneurons are limited to function as output units. Analysis of the network that controls crawling behavior in the leech has clearly indicated that motoneurons, in addition to controlling muscle activity, send signals to the pattern generator. Physiological and modeling studies on the role of specific motoneurons suggest that these feedback signals modulate the phase relationship of the rhythmic activity.

Homo- and Heterobinuclear Cu and Pd Complexes with a Bridging Redox-Active Bisguanidino-Substituted Dioxolene Ligand: Electronic Structure and Metal-Ligand Electron-Transfer.

A new redox-active 4,5-bisguanidino-substituted o-benzoquinone ligand L is synthesized, which allows rational access to heterobinuclear complexes through the sequential coordination of two metals. In the examples discussed in this work, mononuclear Cu and Pd complexes are prepared in a first coordination step, and these complexes are then used as precursors to homobinuclear [CuII -L0 -CuII ] and heterobinuclear [PdII -L0 -CuII ] complexes. In the heterobinuclear complex, the PdII is coordinated by the softer bisguanidine side of L and the CuII by the harder dioxolene side (in line with the HSAB concept). The heterobinuclear complex is in a temperature-dependent equilibrium with its dimer, with two unsymmetrical Cu-Cl-Cu bridges. The redox-chemistry of the [CuII -L-CuII ] and [PdII -L-CuII ] complexes is studied. One-electron oxidation of both complexes was found to be quasi-reversible in CV experiments, and chemical one-electron oxidation was achieved with NO+ (SbF6- ). In the case of the homobinuclear complex [L(CuCl2 )2 ]+ , intramolecular ligand-metal electron-transfer, triggered by coordination of a CH3 CN solvent molecule, leads to a temperature-dependent equilibrium between the form [CuII -L0 -CuIII ] at low temperatures (with CH3 CN coordinated to the CuIII atom) and [CuII -L⋅+ -CuII ] at higher temperatures (without CH3 CN).

Optic neuritis is associated with inner nuclear layer thickening and microcystic macular edema independently of multiple sclerosis.

BACKGROUND: Microcystic macular edema (MME) and inner nuclear layer thickening (INL) were described in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients using optical coherence tomography (OCT). The cause of these findings is currently unknown and a relation to inflammatory or degenerative processes in the optic nerve is discussed. OBJECTIVE: The aim of our study was to investigate whether INL thickening and MME are related to optic neuritis (ON) in various neuro-inflammatory disorders causingON: MS, NMO and chronic inflammatory optic neuropathy. METHODS: We retrospectively analyzed data from 216 MS patients, 39 patients with a clinically isolated syndrome, 20 NMO spectrum disorder patients, 9 patients with chronic inflammatory optic neuropathy and 121 healthy subjects. Intra-retinal layer segmentation was performed for the eyes of patients with unilateral ON. Scanning laser ophthalmoscopy (SLO) images were reviewed for characteristic ocular fundus changes. RESULTS: Intra-retinal layer segmentation showed that eyes with a history of ON displayed MME independent INL thickening compared to contralateral eyes without previous ON. MME was detected in 22 eyes from 15 patients (5.3% of all screened patients), including 7 patients with bilateral edema. Of these, 21 had a prior history of ON (95%). The SLO images of all 22 MME-affected eyes showed crescent-shaped texture changes which were visible in the perifoveal region. A second grader who was blinded to the results of the OCT classified all SLO images for the presence of these characteristic fundus changes. All MME eyes were correctly classified (sensitivity = 100%) with high specificity (95.2%). CONCLUSION: This study shows that both MME and INL thickening occur in various neuro-inflammatory disorders associated with ON. We also demonstrate that detection and analysis of MME by OCT is not limited to B-scans, but also possible using SLO images.

Optical Coherence Tomography Reveals Distinct Patterns of Retinal Damage in Neuromyelitis Optica and Multiple Sclerosis.

BACKGROUND: Neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS) are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT) studies investigating retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL) while rare data are available on deeper intra-retinal layers. OBJECTIVE: To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD) and RRMS with focus on the influence of a previous optic neuritis (ON). METHODS: We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC). Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA) was assessed. RESULTS: NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema. CONCLUSION: Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.

Eye gaze reveals a fast, parallel extraction of the syntax of arithmetic formulas.

Mathematics shares with language an essential reliance on the human capacity for recursion, permitting the generation of an infinite range of embedded expressions from a finite set of symbols. We studied the role of syntax in arithmetic thinking, a neglected component of numerical cognition, by examining eye movement sequences during the calculation of arithmetic expressions. Specifically, we investigated whether, similar to language, an expression has to be scanned sequentially while the nested syntactic structure is being computed or, alternatively, whether this structure can be extracted quickly and in parallel. Our data provide evidence for the latter: fixations sequences were stereotypically organized in clusters that reflected a fast identification of syntactic embeddings. A syntactically relevant pattern of eye movement was observed even when syntax was defined by implicit procedural rules (precedence of multiplication over addition) rather than explicit parentheses. While the total number of fixations was determined by syntax, the duration of each fixation varied with the complexity of the arithmetic operation at each step. These findings provide strong evidence for a syntactic organization for arithmetic thinking, paving the way for further comparative analysis of differences and coincidences in the instantiation of recursion in language and mathematics.

Escorbuto / Scurvy

Apesar de considerado raro, o escorbuto, doença clínica causada pela deficiência de vitamina C, ainda ocorre nos dias de hoje, inclusive em países desenvolvidos. É caracterizada por acometer pacientes com história de alcoolismo, baixo nível socioeconômico, alergia alimentar e doenças psiquiátricas. A causa principal é a insuficiente ingestão de frutas e vegetais frescos. A apresentação clínica consiste de sinais e sintomas inespecíficos. Essas manifestações podem estar associadas ao acometimento de diversos órgãos, como a pele e os sistemas hematológico, articular e ósseo, pois o ácido ascórbico constitui elemento fundamental na formação do componente essencial desses tecidos: o colágeno. O diagnóstico é essencialmente clínico, baseando-se na sintomatologia e história dietética do paciente. O tratamento é feito com reposição de vitamina C em doses que variam de 500mg a 1g por dia, com resultados satisfatórios em curto espaço de tempo. Descrevemos o caso de uma paciente com 24 anos, com manifestações típicas de deficiência de vitamina C, retratando uma apresentação clássica de escorbuto nos dias atuais

Although considered rare, scurvy, a clinical disease caused by deficiency of vitamin C, still occurs today, even in developed countries. It usually affects patients with a history of alcohol abuse, low socio-economic status, food allergy and psychiatric disorders. The main cause is insufficient intake of fresh fruit and vegetables. The clinical presentation consists of nonspecific signs and symptoms. These symptoms may be associated with the involvement of various organs such as the skin and the hematological, joint and bone systems, because ascorbic acid is a crucial element in the formation of collagen, the essential component of these tissues. The diagnosis is essentially clinical, based on symptoms and dietary history of the patient. Treatment is with supplements of vitamin C in doses ranging from 500mg to 1g per day, with satisfactory results in a short time. We report the case of a 24-year female patient with typical manifestations of vitamin C deficiency, featuring a typical presentation of scurvy today