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2.
Neuropsychobiology ; 79(4-5): 345-351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32485705

RESUMO

BACKGROUND: Accumulating neuroimaging evidence suggests that abnormal intrinsic neural activity could underlie auditory verbal hallucinations (AVH) in patients with schizophrenia. However, little is known about the functional interplay between distinct intrinsic neural networks and their association with AVH. METHODS: We investigated functional network connectivity (FNC) of distinct resting-state networks as well as the relationship between FNC strength and AVH symptom severity. Resting-state functional MRI data at 3 T were obtained for 14 healthy controls and 10 patients with schizophrenia presenting with persistent AVH. The data were analyzed using a spatial group independent component analysis, followed by constrained maximal lag correlations to determine FNC within and between groups. RESULTS: Four components of interest, comprising language, attention, executive control networks, as well as the default-mode network (DMN), were selected for subsequent FNC analyses. Patients with persistent AVH showed lower FNC between the language network and the DMN (p < 0.05, corrected for false discovery rate). FNC strength, however, was not significantly related to symptom severity, as measured by the Psychotic Symptom Rating Scale. CONCLUSION: These findings suggest that disrupted FNC between a speech-related system and a network subserving self-referential processing is associated with AVH. The data are consistent with a model of disrupted self-attribution of speech generation and perception.

3.
Eur Neuropsychopharmacol ; 36: 72-82, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32522386

RESUMO

Despite substantial efforts in the last decades, objective measures that can predict clinical outcome in patients with schizophrenia (SZ) after an acute psychotic episode are still lacking. Here, we introduced a comprehensive assessment of sensorimotor function to predict mid-term clinical outcome following an acute psychotic episode. This naturalistic follow-up of 43 patients with DSM-IV-TR diagnosis of SZ examined sensorimotor abnormalities (i.e. Neurological Soft Signs (NSS), parkinsonism, akathisia, catatonia and acute dyskinesia), psychopathology, cognition and psychosocial functioning using well-established instruments. A collection of statistical methods was used to examine the relationship between sensorimotor domain, psychopathology, cognition and psychosocial functioning. We also tested the clinical feasibility of this relationship when predicting clinical outcome after an acute psychotic episode. Longitudinal data were collected on 43 individuals after a follow-up period of >6 months. At follow-up, patients showed significantly reduced general symptom severity, as well as decreased levels of NSS, parkinsonism and catatonia. Further, NSS scores at baseline predicted PANSS negative scores and cognitive functioning at baseline. Finally, NSS scores at baseline predicted symptom change (reduction of PANSS positive and negative scores) at follow-up. In conclusion, our results suggest that NSS are significant predictors of poor clinical outcome in SZ at baseline and >6 months after an acute psychotic episode. These findings propose sensorimotor domain as state biomarker of SZ and support its predictive power with respect to treatment outcome.

4.
Mol Psychiatry ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555423

RESUMO

Psychomotor abnormalities have been abundantly observed in psychiatric disorders like major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCH). Although early psychopathological descriptions highlighted the truly psychomotor nature of these abnormalities, more recent investigations conceive them rather in purely motor terms. This has led to an emphasis of dopamine-based abnormalities in subcortical-cortical circuits including substantia nigra, basal ganglia, thalamus, and motor cortex. Following recent findings in MDD, BD, and SCH, we suggest a concept of psychomotor symptoms in the literal sense of the term by highlighting three specifically psychomotor (rather than motor) mechanisms including their biochemical modulation. These include: (i) modulation of dopamine- and substantia nigra-based subcortical-cortical motor circuit by primarily non-motor subcortical raphe nucleus and serotonin via basal ganglia and thalamus (as well as by other neurotransmitters like glutamate and GABA); (ii) modulation of motor cortex and motor network by non-motor cortical networks like default-mode network and sensory networks; (iii) global activity in cortex may also shape regional distribution of neural activity in motor cortex. We demonstrate that these three psychomotor mechanisms and their underlying biochemical modulation are operative in both healthy subjects as well as in MDD, BD, and SCH subjects; the only difference consists in the fact that these mechanisms are abnormally balanced and thus manifest in extreme values in psychiatric disorders. We conclude that psychomotor mechanisms operate in a dimensional and cross-nosological way as their degrees of expression are related to levels of psychomotor activity (across different disorders) rather than to the diagnostic categories themselves. Psychomotor mechanisms and their biochemical modulation can be considered paradigmatic examples of a dimensional approach as suggested in RDoC and the recently introduced spatiotemporal psychopathology.

5.
Chemistry ; 26(35): 7736, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32500555

RESUMO

Invited for the cover of this issue are the groups of Ruth M. Gschwind and Robert Wolf (University of Regensburg), Christian Müller (Freie Universität Berlin), and J. Chris Slootweg (University of Amsterdam). The image depicts playing cards representing the reported reactions involving 1-phospha-7-bora-norbornadiene. Read the full text of the article at 10.1002/chem.202000266.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32505809

RESUMO

Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) population. The objective of this cross-sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo-HSCT. An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow-up after allo-HSCT. Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses. In the entire cohort, 51% of subjects (n = 102) reported nonadherence to nonimmunosuppressant medications (95% confidence interval [CI], 44.07% to 57.93%) on the Morisky Medication Adherence Scale. Of the 153 patients taking oral immunosuppressant medications at the time of the survey, 58 (37.9%) reported nonadherence to immunosuppressant therapy (95% CI, 30.22% to 45.6%), as measured by the Immunosuppressant Therapy Adherence Scale. Younger age and distress were associated with medication nonadherence. Nonadherence to immunosuppressant therapy was associated with mild chronic graft-vs-host disease (cGVHD), and a similar trend was observed for moderate cGVHD. Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo-HSCT recipient, and further study to identify interventions to improve adherence in these patients is warranted.

7.
Chemistry ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32484989

RESUMO

Unsymmetrically substituted tertiary phosphines and quaternary phosphonium salts are used extensively in applications throughout industry and academia. Despite their significance, classical methods to synthesize such compounds demand either harsh reaction conditions, prefunctionalization of starting materials, highly sensitive organometallic reagents, or expensive transition metal catalysts. Mild, practical methods thus remain elusive, despite being of great current interest. Herein, we describe a visible light-driven method to form these products from secondary and primary phosphines. Using an inexpensive organic photocatalyst and blue light irradiation, arylphosphines can be both alkylated and arylated using commercially available organohalides. In addition, the same organocatalyst can be used to transform white phosphorus (P4) directly into symmetrical aryl phosphines and phosphonium salts in a single reaction step, which has previously only been possible using precious metal catalysis.

8.
Chemistry ; 26(28): 6089, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32350956

RESUMO

Invited for the cover of this issue is the group of Robert Wolf at the University of Regensburg and colleagues at the University of Hamburg. The image depicts the hydrogenation of triphenylethylene. Read the full text of the article at 10.1002/chem.201905537.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32369829

RESUMO

Catatonia is characterized by motor, affective and behavioral abnormalities. To date, the specific role of white matter (WM) abnormalities in schizophrenia spectrum disorders (SSD) patients with catatonia is largely unknown. In this study, diffusion magnetic resonance imaging (dMRI) data were collected from 111 right-handed SSD patients and 28 healthy controls. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). We used whole-brain tract-based spatial statistics (TBSS), tractometry (along tract statistics using TractSeg) and graph analytics (clustering coefficient-CCO, local betweenness centrality-BC) to provide a framework of specific WM microstructural abnormalities underlying catatonia in SSD. Following a categorical approach, post hoc analyses showed differences in fractional anisotrophy (FA) measured via tractometry in the corpus callosum, corticospinal tract and thalamo-premotor tract as well as increased CCO as derived by graph analytics of the right superior parietal cortex (SPC) and left caudate nucleus in catatonic patients (NCRS total score ≥ 3; n = 30) when compared to non-catatonic patients (NCRS total score = 0; n = 29). In catatonic patients according to DSM-IV-TR (n = 43), catatonic symptoms were associated with FA variations (tractometry) of the left corticospinal tract and CCO of the left orbitofrontal cortex, primary motor cortex, supplementary motor area and putamen. This study supports the notion that structural reorganization of WM bundles connecting orbitofrontal/parietal, thalamic and striatal regions contribute to catatonia in SSD patients.

10.
Addict Behav ; 108: 106422, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32403056

RESUMO

Popularity of smartphones has dramatically increased in the past years, accompanied by increased concerns regarding potentially adverse effects on physical and mental health. Addictive behavior associated with excessive smartphone use, frequently referred to as "smartphone addiction" (SPA), has attracted increased scientific interest. However the neural correlates of SPA are unknown. We used functional magnetic resonance imaging at 3T to investigate the neural correlates of cue reactivity (CR) in individuals with SPA (n = 21) compared to controls (n = 21). SPA was assessed using the Smartphone Addiction Inventory (SPAI), and neural activity was measured by a modified CR task. Contrasts of images of smartphones vs. neutral stimuli and stimuli including active vs. inactive smartphones (p < 0.001, uncorrected for height, followed by correction for spatial extent) were analyzed. In the first contrast, group differences in medial prefrontal (MPFC), occipital, temporal, and anterior cingulate (ACC) cortices, in temporoparietal regions, and cerebellum were found. For active vs. inactive smartphones, group differences were found in frontal operculum/anterior insula and precentral gyrus. Negative correlations were found between MPFC, ACC, precuneus, and precentral gyrus and specific SPAI subscores, i.e. compulsive behavior, functional impairment and withdrawal. This study suggests spatial similarities of CR-related brain activation between addictive smartphone use and other well-known addictive disorders.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32358546

RESUMO

We conducted a retrospective study comparing posttransplant outcomes between myeloma patients receiving conditioning melphalan on day-2 vs day-1 for autologous stem cell transplant. Between January 2017 and December 2018, 201 patients received melphalan on day-2 and 166 on day-1 prior to stem cell infusion. Baseline disease and clinical characteristics between the two groups were similar. Although rates of hospitalization were similar between the cohorts, duration of hospital admission was longer for day-1 (median 7 days for day-1 vs 5 days for day-2, p = 0.003). Rates of fever were higher in the day-1 cohort (69% vs 49%, p = 0.0002). Time to platelet and neutrophil engraftment was significantly longer in the day-1 cohort (platelet engraftment median days 17 for day-1 vs 15 for day-2, p < 0.0001, neutrophil engraftment median days 16 for day-1 vs 16 for day-2, p = 0.025). Overall response rate was similar between the cohorts (99% for day-1, vs 100% for day-2). Day-2 melphalan infusions should be considered in preference for day-1 protocols, given the clinically significant delay in platelet and neutrophil engraftment and longer duration of hospitalization with day-1 infusions.

12.
Invest Ophthalmol Vis Sci ; 61(4): 36, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32334431

RESUMO

Purpose: To examine the extent of visual function abnormality outside the dark lesion on short-wavelength fundus autofluorescence (SW-AF), and its correlation with background SW-AF features and optical coherence tomography (OCT) in recessive Stargardt disease (STGD1). Methods: Forty-nine eyes of 25 participants in the ProgStar (the Natural History of the Progression of Atrophy Secondary to Stargardt Disease) study at our center were included. Patients underwent microperimetry (both threshold and dense scotoma mapping), OCT, SW-AF, and visual acuity testing. The Fisher's exact test, the χ2 test, and unpaired t-tests were used to analyze the data. Results: Of 40 eyes without central fixation, 33 (82%) placed fixation remote (most ≥5°) from the dense scotoma edge, despite good intervening retinal sensitivity. OCT findings accounted for the remote fixation in 75%. Eighteen (37%) of all 49 eyes had dense scotoma extending past the dark lesion border. OCT was not adequate to define the edge of the scotoma. Of the 49 eyes, 28 (57%) had the mottled background pattern, 10 (20%) had the uniform pattern, and 11 (22%) had the other pattern, with >75% of eyes in each pattern having remote fixation. The dense scotoma exceeded the dark lesion primarily in the mottled pattern. The two eyes of each patient were concordant in all features. Conclusions: Functional abnormalities in STGD1 extend past the SW-AF dark lesion. The disruption of the ellipsoid zone shows that photoreceptor abnormality extends peripheral to the dark lesion, and it explains in part the remote fixation pattern and the dense scotoma exceeding the dark lesion. This has implications for clinical trials for STGD1.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32348622

RESUMO

The reaction of zerovalent nickel compounds with white phosphorus (P4 ) is a barely explored route to binary nickel phosphide clusters. Here, we show that coordinatively and electronically unsaturated N-heterocyclic carbene (NHC) nickel(0) complexes afford unusual cluster compounds with P1 , P3 , P5 and P8 units. Using [Ni(IMes)2 ] [IMes=1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene], electron-deficient Ni3 P4 and Ni3 P6 clusters have been isolated, which can be described as superhypercloso and hypercloso clusters according to the Wade-Mingos rules. Use of the bulkier NHC complexes [Ni(IPr)2 ] or [(IPr)Ni(η6 -toluene)] [IPr=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene] affords a closo-Ni3 P8 cluster. Inverse-sandwich complexes [(NHC)2 Ni2 P5 ] (NHC=IMes, IPr) with an aromatic cyclo-P5 - ligand were identified as additional products.

14.
Neuropsychobiology ; 79(4-5): 335-344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160619

RESUMO

INTRODUCTION: Delusions are core symptoms of schizophrenia-spectrum and related disorders. Despite their clinical relevance, the neural correlates underlying such phenomena are unclear. Recent research suggests that specific delusional content may be associated with distinct neural substrates. OBJECTIVE: Here, we used structural magnetic resonance imaging to investigate multiple parameters of brain morphology in patients presenting with paranoid type delusional disorder (pt-DD, n = 14) compared to those of healthy controls (HC, n = 25). METHODS: Voxel- and surface-based morphometry for structural data was used to investigate gray matter volume (GMV), cortical thickness (CT) and gyrification. RESULTS: Compared to HC, patients with pt-DD showed reduced GMV in bilateral amygdala and right inferior frontal gyrus. Higher GMV in patients was found in bilateral orbitofrontal and in left superior frontal cortices. Patients also had lower CT in frontal and temporal regions. Abnormal gyrification in patients was evident in frontal and temporal areas, as well as in bilateral insula. CONCLUSIONS: The data suggest the presence of aberrant GMV in a right prefrontal region associated with belief evaluation, as well as distinct structural abnormalities in areas that essentially subserve processing of fear, anxiety and threat in patients with pt-DD. It is possible that cortical features of distinct evolutionary and genetic origin, i.e. CT and gyrification, contribute differently to the pathogenesis of pt-DD.

15.
Leuk Lymphoma ; 61(7): 1592-1600, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32157935

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation in children that is increasingly being recognized in adults. Efficacy data for the HLH-04 protocol in adults is lacking. This study retrospectively analyzed 31 adult patients, median age 46 years, who received HLH-04 from 1/1/2004 to 5/1/2018. HLH etiology included malignancy (n = 9), autoimmune (n = 8), infection (n = 8), and idiopathic (n = 6). Eighteen patients were evaluable for response at week 4 with 7 having no response, 11 reaching partial response, and 0 reaching complete response (CR). Six patients eventually achieved CR at a median 195 days. The 1-year overall survival (OS) was 35% and median OS was 3.2 months. Univariate analysis showed shorter survival for hemoglobin <9 g/dL (HR 4.29, p = 0.003), platelets <100 × 109/L (HR 4.06, p = 0.027), ANC <1 × 109/L (HR 5.24, p = 0.001), and total bilirubin >1.2 mg/dL (HR 3.30, p = 0.022). Outcomes of adults treated with HLH-04 remain dismal and newer treatment modalities are needed.

16.
Schizophr Bull ; 46(4): 999-1008, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32162660

RESUMO

Motor abnormalities in schizophrenia spectrum disorders (SSD) have increasingly attracted scientific interest in the past years. However, the neural mechanisms underlying parkinsonism in SSD are unclear. The present multimodal magnetic resonance imaging (MRI) study examined SSD patients with and without parkinsonism, as defined by a Simpson and Angus Scale (SAS) total score of ≥4 (SAS group, n = 22) or <4 (non-SAS group, n = 22). Parallel independent component analysis (p-ICA) was used to examine the covarying components among gray matter volume maps computed from structural MRI (sMRI) and fractional amplitude of low-frequency fluctuations (fALFF) maps computed from resting-state functional MRI (rs-fMRI) patient data. We found a significant correlation (P = .020, false discovery rate [FDR] corrected) between an sMRI component and an rs-fMRI component, which also significantly differed between the SAS and non-SAS group (P = .042, z = -2.04). The rs-fMRI component comprised the cortical sensorimotor network, and the sMRI component included predominantly a frontothalamic/cerebellar network. Across the patient sample, correlations adjusted for the Positive and Negative Syndrome Scale (PANSS) total scores showed a significant relationship between tremor score and loadings of the cortical sensorimotor network, as well as between glabella-salivation score, frontothalamic/cerebellar and cortical sensorimotor network loadings. These data provide novel insights into neural mechanisms of parkinsonism in SSD. Aberrant bottom-up modulation of cortical motor regions may account for these specific motor symptoms, at least in patients with SSD.

17.
Chemistry ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052879

RESUMO

Salt metathesis of 1-methyl-2,4,6-triphenylphosphacyclohexadienyl lithium and chlorobis(pentafluorophenyl)borane affords a 1-phospha-7-bora-norbornadiene derivative 2. The C≡N triple bonds of nitriles insert into the P-B bond of 2 with concomitant C-B bond cleavage, whereas the C≡C bonds of phenylacetylenes react with 2 to form λ4 -phosphabarrelenes. Even though 2 must formally be regarded as a classical Lewis adduct, the C≡N and C≡C activation processes observed (and the mild conditions under which they occur) are reminiscent of the reactivity of frustrated Lewis pairs. Indeed, NMR and computational studies give insight into the mechanism of the reactions and reveal the labile nature of the phosphorus-boron bond in 2, which is also suggested by detailed NMR spectroscopic studies on this compound. Nitrile insertion is thus preceded by ring opening of the bicycle of 2 through P-B bond splitting with a low energy barrier. By contrast, the reaction with alkynes involves formation of a reactive zwitterionic methylphosphininium borate intermediate, which readily undergoes alkyne 1,4-addition.

18.
Eur J Pain ; 24(5): 945-955, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32061140

RESUMO

BACKGROUND: Modulation of pain perception by oxytocin (OXT) has attracted increased scientific and clinical interest. Neural mechanisms underlying these effects are poorly understood. In this study, we aimed to investigate the effects of intranasally applied OXT on intrinsic neural activity in patients with chronic low back pain (cLBP). METHODS: Twenty-four male patients with cLBP and 23 healthy males were examined using resting-state functional magnetic resonance imaging. Participants were scanned twice and received either intranasally applied OXT (24 international units) or placebo 40 min before scanning. The fractional amplitude of low-frequency fluctuations (fALFF) was computed to investigate regionally specific effects of OXT on intrinsic neural activity. In addition a multivariate statistical data analysis strategy was employed to explore OXT-effects on functional network strength. RESULTS: Differential effects of OXT were observed in cLBP and healthy controls. FALFF decreased in left nucleus accumbens and right thalamus in cLBP and increased in right thalamus in healthy controls after OXT application compared to placebo. OXT also induced activity changes in bilateral thalamus, left caudate nucleus and right amygdala in cLBP. OXT was associated with increased medial frontal, parietal and occipital functional network strength, though this effect was not group-specific. Regression analyses revealed significant associations between left nucleus accumbens, left caudate nucleus and right amygdala with pain-specific psychometric scores in cLBP. CONCLUSIONS: These data suggest OXT-related modulation of regional activity and neural network strength in patients with cLBP and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by OXT. SIGNIFICANCE: Our data suggest significant oxytocin-related modulation of intrinsic regional activity and neural network strength in patients with chronic low back pain and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by oxytocin. Therapeutic effects of oxytocin for improved pain treatment need to be further investigated.

19.
Chemistry ; 26(28): 6113-6117, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32034810

RESUMO

The hydrogenation of olefins, styrenes, enoates, imines, and sterically hindered tri-substituted olefins was accomplished using the pre-catalyst dilithiumbis(cycloocta-1,5-diene)nickelate(-II) (1). The mild conditions tolerate hydroxyl, halide, ester, and lactone functionalities. Mechanistic studies, including reaction progress analyses, poisoning experiments, and multinuclear NMR monitoring, indicate that a heterotopic (nickel nanoparticle) catalyst is in operation.

20.
Addict Behav ; 105: 106334, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32062336

RESUMO

Popularity and availability of smartphones have dramatically increased in the past years. This trend is accompanied by increased concerns regarding potentially adverse effects of excessive smartphone use, particularly with respect to physical and mental health. Recently, the term "smartphone addiction" (SPA) has been introduced to describe smartphone-related addictive behavior and associated physical and psychosocial impairment. Here, we used structural and functional magnetic resonance imaging (MRI) at 3 T to investigate gray matter volume (GMV) and intrinsic neural activity in individuals with SPA (n = 22) compared to a control group (n = 26). SPA was assessed using the Smartphone Addiction Inventory (SPAI), GMV was investigated by means of voxel-based morphometry, and intrinsic neural activity was measured by the amplitude of low frequency fluctuations (ALFF). Compared to controls, individuals with SPA showed lower GMV in left anterior insula, inferior temporal and parahippocampal cortex (p < 0.001, uncorrected for height, followed by correction for spatial extent). Lower intrinsic activity in SPA was found in the right anterior cingulate cortex (ACC). A significant negative association was found between SPAI and both ACC volume and activity. In addition, a significant negative association between SPAI scores and left orbitofrontal GMV was found. This study provides first evidence for distinct structural and functional correlates of behavioral addiction in individuals meeting psychometric criteria for SPA. Given their widespread use and increasing popularity, the present study questions the harmlessness of smartphones, at least in individuals that may be at increased risk for developing smartphone-related addictive behaviors.

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