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Berlin Brandenburg

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  • 1
    In: Brain, 2017, Vol. 140(7), pp.1818-1820
    Description: This scientific commentary refers to ‘Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome’, by Kuchcinski et al . (doi: 10.1093/brain/awx114 ).
    Keywords: Iron ; Thalamus ; Abridged ; Iron;
    ISSN: 0006-8950
    E-ISSN: 1460-2156
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  • 2
    In: Neurology, 2015, Vol.84(23), pp.2300-2301
    Keywords: Brain Diseases–Blood ; Cognition Disorders–Blood ; Diabetes Complications–Blood ; Diabetes Mellitus–Blood ; Female–Blood ; Humans–Blood ; Male–Blood ; Abridged;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 3
    Language: English
    In: The Journal of Allergy and Clinical Immunology, November 2018, Vol.142(5), pp.1650-1653.e2
    Description: The consequences of PI3Kδ deficiency have been extensively characterized in mice, providing much of our knowledge on the biological role of PI3Kδ, such as its involvement in early development of B cells and regulation of adaptive immune responses.2 Heterozygous gain-of-function mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit δ gene (PIK3CD; the gene encoding p110δ) cause a primary immunodeficiency disorder characterized by both immunodeficiency and immune dysregulation (activated PI3Kδ syndrome). At the age of 8 years, he had recurrent diarrhea caused by inflammatory colitis, which was diagnosed as Crohn disease and successfully treated with mesalazine for approximately 2 years. Since the age of 12 years, he had recurrent respiratory tract infections, including 2 cases of severe pneumonia that required hospitalization and administration of intravenous antibiotics. Sorted cells were cultured in RPMI 1640 medium/10% FCS for 30 minutes in the presence of IC87114 (Merck, Whitehouse Station, NJ) or an equal amount of dimethyl sulfoxide and were subsequently stimulated with anti-CD3 antibody for 10 minutes, as described previously.E2 Cells were then permeabilized and prepared for staining with the Transcription Factor Phospho Buffer Set (BD Biosciences), according to the manufacturer's protocol; stained with an Alexa Fluor 647–conjugated mAb against phospho-AKT (Ser473; Cell Signaling, Danvers, Mass); and analyzed with a FACSCalibur flow cytometer (Becton Dickinson). Deceased patient Living patient Year of birth 1994 1995 Sex Male Male Infections Recurrent sinopulmonary infections since infancy, including 1 case of pneumonia accompanied by Streptococcus pneumoniae sepsis, chronic diarrhea (diagnosed as postenteritis syndrome) Osteomyelitis at age of 8 months, recurrent sinopulmonary infections since the 12th year of life, including 2 cases of severe pneumonia Other clinical manifestations Chronic diarrhea (diagnosed as postenteritis syndrome) Diagnosis of Crohn disease at age 12 years, diagnosis of psoriasis at age 18 years Serum immunoglobulin concentration IgG (g/L) 2.83 (5-13)∗ 2.7 (7-16) IgA (g/L) 0.16 (0.4-1.8) 0.3 (0.7-4) IgM (g/L) 165 (90-150) 〉165 (90-150) C3c (g/L) 1.55 (0.9-1.8) 1.22 (0.9-1.8) C4 (g/L) 0.38 (0.1-0.4) 0.26 (0.1-0.4) Lymphocyte subset analysis Lymphocyte count (cells/μL) 4,560 (1,700-6,900) 2,204 (1,000-2,800) CD3+ (relative %) 72% (43% to 76%) 80% (55% to 83%) CD3+CD4+ (relative %) 37% (23% to 48%) 37.3% (28% to 57%) CD3+CD8+ (relative %) 30% (14% to 33%) 40.1% (10% to 39%) CD3−CD16+CD56+ (relative %) 10.2% (4% to 23%) 8.4% (7% to 31%) CD19+ (relative %) 0.6% (14% to 44%) 1.3% (6% to 19%) Lymphocyte proliferation assay PHA (cells/μL) 45,567 (34,797) 34,298 (32,100) Concanavalin A (cells/μL) 22,032 (21,560) 8,208 (6,234) Pokeweed mitogen (cells/μL) NM 9,644 (11,001) IL-2 (cells/μL) 5,743 (4,734) 3,340 (4,011) Anti-CD3 antibody (cells/μL) 21,440 (20,674) 22,012 (25,325) Granulocyte phenotyping CD16 (%) NM 93 (96) CD32 (%) NM 100 (100) CD64 (%) NM 13 (1) CD18 (%) NM 100 (100) CD11b (%) NM 100 (100) CD15 (%) NM 94 (99) Granulocyte function tests Phagocytosis of Escherichia coli (%) 96 (100) 98 (99) Oxidative burst induction N-formyl-methionyl-leucyl-phenylalanine (%) NM 35 (8) E coli (%) 94 (96) 98 (100) Phorbol 12-myristate 13-acetate (%) 100 (99) 100 (100) NK cell activity Natural cytotoxicity (1:30) 5 (27) 4 (30) ADCC (1:30) 9 (42) 11 (58) Table I Characteristics of patients with PI3Kδ deficiency Lymphocytes 2204 cells/μL (38% of leukocytes) CD19+ B cells 1.3% CD27−IgM+IgD+ naive B cells 1% CD27+IgM+IgD+ memory B cells 0.1% CD27+IgM−IgD− switched memory B cells 0% CD38++IgM++ transitional B cells 0.1% CD38+++IgM−/+ plasma cells 0.1% CD21lowCD38low B cells 0% CD16+CD56+CD3− NK cells 8.4% CD3+ T cells 80% CD3+CD4+ helper cells 37.3 % CD3+CD8+ cytotoxic T cells 40.1% CD3+TCR2+ α/β T cells 65.8% CD4/CD8 double-negative TCR2+ cells 0.6% CD4+CD45RO+ CD4 memory cells 14.7% Circulating CXCR5+CD4+ T cells 1.8% CD4+CD25+CD127low regulatory T cells 3.1% CD4+CD45RA+ naive CD4 T cells 20% CD4+CD45RA+CD31+ recent thymic emigrant T cells 14.7% CD8+CD27−CD28− late CD8 effector cells 15.2% CD8+CD27+CD28− effector cells 3% Table E1 Peripheral B- and T-lymphocyte subsets in a patient aged 16 years with PI3Kδ deficiency
    Keywords: Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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  • 4
    In: Stroke, 2017, Vol.48(9), pp.2583-2585
    Description: BACKGROUND AND PURPOSE—: Dysphagia is a common stroke symptom and leads to serious complications such as aspiration and pneumonia. Early dysphagia screening can reduce these complications. In many hospitals, dysphagia screening is performed by speech–language therapists who are often not available on weekends/holidays, which results in delayed dysphagia assessment. METHODS—: We trained the nurses of our neurological department to perform formal dysphagia screening in every acute stroke patient by using the Gugging Swallowing Screen. The impact of a 24/7 dysphagia screening (intervention) over swallowing assessment by speech–language therapists during regular working hours only was compared in two 5-month periods with time to dysphagia screening, pneumonia rate, and length of hospitalization as outcome variables. RESULTS—: Overall, 384 patients (mean age, 72.3±13.7 years; median National Institutes of Health Stroke Scale score of 3) were included in the study. Both groups (pre-intervention, n=198 versus post-intervention, n=186) were comparable regarding age, sex, and stroke severity. Time to dysphagia screening was significantly reduced in the intervention group (median, 7 hours; range, 1–69 hours) compared with the control group (median, 20 hours; range, 1–183; P=0.001). Patients in the intervention group had a lower rate of pneumonia (3.8% versus 11.6%; P=0.004) and also a reduced length of hospital stay (median, 8 days; range, 2–40 versus median, 9 days; range, 1–61 days; P=0.033). CONCLUSIONS—: 24/7 dysphagia screening can be effectively performed by nurses and leads to reduced pneumonia rates. Therefore, empowering nurses to do a formal bedside screening for swallowing dysfunction in stroke patients timely after admission is warranted whenever speech–language therapists are not available.
    Keywords: Aged–Diagnosis ; Aged, 80 and Over–Epidemiology ; Deglutition Disorders–Epidemiology ; Female–Epidemiology ; Humans–Nursing ; Length of Stay–Nursing ; Male–Nursing ; Mass Screening–Nursing ; Middle Aged–Nursing ; Nursing Assessment–Nursing ; Pneumonia–Nursing ; Pneumonia, Aspiration–Nursing ; Severity of Illness Index–Nursing ; Stroke–Nursing ; Time Factors–Nursing ; Deglutition Disorders ; Nursing ; Pneumonia ; Stroke;
    ISSN: 0039-2499
    E-ISSN: 15244628
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  • 5
    In: Stroke, 2016, Vol.47(5), pp.1258-1264
    Description: BACKGROUND AND PURPOSE—: Lacunes are a major manifestation of cerebral small vessel disease. Although still debated, the morphological features of lacunes may offer mechanistic insights. We systematically analyzed the shape of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetically defined small vessel disease. METHODS—: A total of 88 incident lacunes from 57 patients were segmented from 3-dimensional T1 magnetic resonance images and 3 dimensionally reconstructed. Anatomic location, diameter, volume, surface area, and compactness of lacunes were assessed. The shape was analyzed using a size, orientation, and position invariant spectral shape descriptor. We further investigated the relationship with perforating arteries and fiber tracts. RESULTS—: Lacunes were most abundant in the centrum semiovale and the basal ganglia. Diameter, volume, and surface area of lacunes in the basal ganglia and centrum semiovale were larger than in other brain regions. The spectral shape descriptor revealed a continuum of shapes with no evidence for distinct classes of lacunes. Shapes varied mostly in elongation and planarity. The main axis and plane of lacunes were found to align with the orientation of perforating arteries but not with fiber tracts. CONCLUSIONS—: Elongation and planarity are the primary shape principles of lacunes. Their main axis and plane align with perforating arteries. Our findings add to current concepts on the mechanisms of lacunes.
    Keywords: Medicine;
    ISSN: 0039-2499
    E-ISSN: 15244628
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  • 6
    Language: English
    In: Journal of Neurology, Neurosurgery and Psychiatry, Jan, 2011, Vol.82(1), p.52(6)
    Description: OBJECTIVE: Although age-related confluent white-matter lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML. METHODS: Among 100 patients with ischaemic stroke with confluent WML on MRI, the authors assessed executive function and global cognition by the Mattis Dementia Rating Scale-Initiation/Perseveration Subscale (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric measures were corrected for intracranial volume. The authors investigated the association between basic demography, vascular risk factors, APOE status, WML volume, infarct measures (volume, number, location), microbleed number, atrophy measures (global, central, regional) and cognitive performance. The authors also performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired patients with stroke. RESULTS: WML was no longer related to cognitive performance after adding atrophy into regression equations. Multivariate regression models showed that cortical grey matter volume independently accounted for performance on both the MDRS I/P ( beta =0.241, p=0.045) and MMSE ( beta =0.243, p=0.032). Models examining frontal subregions revealed that volumes of both left ( beta =0.424, p〈0.001) and right ( beta =0.219, p=0.045) lateral frontal orbital gyri predicted MDRS I/P, whereas education ( beta =0.385, p〈0.001) and left lateral frontal orbital gyrus ( beta =0.222, p=0.037) predicted MMSE. Volumes of WML and cognitively relevant brain regions were significantly associated. Seven patients with PIB imaging showed no uptake pattern typical of Alzheimer's disease, suggesting a predominantly vascular aetiology for the cognitive impairment and brain changes in these patients. CONCLUSIONS: Cognitive impairment in patients with confluent WML is mediated by global and frontal cortical atrophy.
    Keywords: Cognitive Disorders -- Demographic Aspects ; Cognitive Disorders -- Development And Progression ; Cognitive Disorders -- Research ; Atrophy -- Development And Progression ; Atrophy -- Demographic Aspects ; Atrophy -- Research ; Cerebral Cortex -- Physiological Aspects ; Cerebral Cortex -- Research ; Frontal Lobes -- Physiological Aspects ; Frontal Lobes -- Research
    ISSN: 0022-3050
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(6), p.e0178371
    Description: Several quantitative magnetic resonance imaging (MRI) techniques have been proposed to investigate microstructural tissue changes in amyotrophic lateral sclerosis (ALS) including diffusion tensor imaging (DTI), magnetization transfer imaging, and R2* mapping. Here, in this study, we compared these techniques with regard to their capability for detecting ALS related white matter (WM) changes in the brain and their association with clinical findings. We examined 27 ALS patients and 35 age-matched healthy controls. MRI was performed at 3T, after which we analyzed the diffusion properties, the magnetization transfer ratio (MTR), and the effective transversal relaxation rate R2* in 18 WM tracts that were obtained by a fully automated segmentation technique. ALS patients, especially with a bulbar onset, showed a bilateral increase in radial and mean diffusivity, as well as a reduction in fractional anisotropy of the corticospinal tract (CST), and diffusion changes in the parietal and temporal superior longitudinal fasciculus. A reduction of the MTR was found in both CSTs and an R2* reduction was seen only in the left CST. Tract-specific diffusion properties were not related to clinical status in a cross-sectional manner but demonstrated some association with disease progression over three subsequent months. DTI reveals more widespread WM tissue changes than MTR and R2*. These changes are not restricted to the CST, but affect also other WM tracts (especially in patients with bulbar onset), and are associated with the short term course of the disease.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    In: PLoS ONE, 2012, Vol.7(8)
    Description: Objectives Resting state (RS) functional MRI recently identified default network abnormalities related to cognitive impairment in MS. fMRI can also be used to map functional connectivity (FC) while the brain is at rest and not adhered to a specific task. Given the importance of the anterior cingulate cortex (ACC) for higher executive functioning in MS, we here used the ACC as seed-point to test for differences and similarities in RS-FC related to sustained attention between MS patients and controls. Design Block-design rest phases of 3 Tesla fMRI data were analyzed to assess RS-FC in 31 patients (10 clinically isolated syndromes, 16 relapsing-remitting, 5 secondary progressive MS) and 31 age- and gender matched healthy controls (HC). Participants underwent extensive cognitive testing. Observations In both groups, signal changes in several brain areas demonstrated significant correlation with RS-activity in the ACC. These comprised the posterior cingulate cortex (PCC), insular cortices, the right caudate, right middle temporal gyrus, angular gyri, the right hippocampus, and the cerebellum. Compared to HC, patients showed increased FC between the ACC and the left angular gyrus, left PCC, and right postcentral gyrus. Better cognitive performance in the patients was associated with increased FC to the cerebellum, middle temporal gyrus, occipital pole, and the angular gyrus. Conclusion We provide evidence for adaptive changes in RS-FC in MS patients compared to HC in a sustained attention network. These results extend and partly mirror findings of task-related fMRI, suggesting FC may increase our understanding of cognitive dysfunction in MS.
    Keywords: Research Article ; Biology ; Medicine ; Social And Behavioral Sciences
    E-ISSN: 1932-6203
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  • 9
    Language: English
    In: Diabetes, 2013, Vol.62(7), pp.2539-2544
    Description: textabstractWe investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during longterm insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m2, and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography- tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (〈0.2 ng/mL) to 1.5 ng/mL (0.9-2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P 〈 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes.
    Keywords: Drug Metabolism -- Research ; Insulin Glargine -- Dosage And Administration ; Insulin Glargine -- Complications And Side Effects ; Type 2 Diabetes -- Drug Therapy ; Type 2 Diabetes -- Genetic Aspects ; Type 2 Diabetes -- Research;
    ISSN: 00121797
    E-ISSN: 1939327X
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  • 10
    In: AIDS, 2018, Vol.32(3), pp.299-307
    Description: OBJECTIVE:: The formation of large intracellular protein aggregates of the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain; also know as PYCARD) is a hallmark of inflammasome activation. ASC speck-forming cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space during pyroptotic cell death. There ASC specks can propagate inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection triggers inflammasome activation of abortively infected CD4 T cells in secondary lymphatic tissues. However, if pyroptosis occurs in other peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients is currently unknown. We investigated if ASC speck positive cells are present in the circulation of HIV-1-infected patients. DESIGN AND METHODS:: PBMCs or plasma of HIV-1 infected, antiretroviral therapy-naive patients were analyzed for the presence of ASC speck cells or extracellular ASC and compared with healthy controls. Intracellular staining for ASC was employed to detect ASC speck cells within PBMCs by flow cytometry, and ELISA to detect free ASC in the plasma. ASC multimerization was confirmed by immunoblot. RESULTS:: Peripheral blood CD14CD16 monocytes were ASC speck in HIV patients, but not in healthy controls. In the subgroup analysis, HIV patients with lower CD4 T-cell counts and higher viral load had significantly more ASC speck monocytes. ASC speck formation did not correlate with Gag expression, coinfection, lactate dehydrogenase or C-reactive protein. CONCLUSION:: Our findings suggest that pyroptotic CD14CD16 classical monocytes of HIV-1-infected patients release ASC specks into the blood stream, a phenomenon that may contribute to HIV-1 induced inflammation and immune activation.
    Keywords: CARD Signaling Adaptor Proteins -- Analysis ; HIV Infections -- Pathology ; Inflammasomes -- Metabolism ; Monocytes -- Chemistry;
    ISSN: 0269-9370
    E-ISSN: 14735571
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