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Event-related fMRI responses were recorded during a recognition memory test for previously studied visual objects. Some studied objects were superimposed on the same context (landscape scenes) as at study, some were superimposed on a different studied context, and some were paired with new contexts. Unstudied objects were paired with either a studied or a new context. Relative to all other stimulus classes, test stimuli where both components were unstudied elicited enhanced responses in lateral and ventral extrastriate visual cortex. This effect, which is analogous to a previously described electrophysiological result obtained with the same experimental procedure, had the same magnitude regardless of whether a test item was composed of one or two studied components, or whether a single studied component was task relevant or task irrelevant. The findings point to the existence of repetition-sensitive neural mechanisms that operate in a non-linear manner. Hum. Brain Mapping 19:145–154, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims: We assessed the association between insulin resistance and blood glucose concentrations at type 2 diabetes diagnosis and future development of diabetes-related complications and mortality., Materials and Methods: This retrospective cohort study included 864 individuals with type 2 diabetes (median age 60 years) whose fasting C-peptide and HbA1c were measured at diabetes diagnosis. The median follow-up time until death or study end was 16.4 years (interquartile range 13.3-19.6). The association between C-peptide and mortality/complications was estimated by Cox regression adjusted for sex, age at diabetes diagnosis, smoking, hypertension, BMI, total cholesterol, and HbA1c. C-peptide and HbA1c were converted to Z scores before the Cox regression analysis., Results: An increase by one standard deviation in fasting C-peptide at diabetes diagnosis was associated with all-cause (hazard ratio [HR] 1.33; 95% confidence intervals [CI] 1.12-1.58; p = 0.001) and cancer mortality (HR 1.51; 95% CI 1.13-2.01; p = 0.005) in the fully adjusted model. An increase by one standard deviation in HbA1c at diabetes diagnosis was associated with all-cause mortality (HR 1.24; 95% CI 1.07-1.44; p = 0.005), major cardiovascular events (HR 1.20; 95% CI 1.04-1.39; p = 0.015), stroke (HR 1.36; 95% CI 1.09-1.70; p = 0.006), and retinopathy (HR 1.54; 95% CI 1.34-1.76; p < 0.0001) in the fully adjusted model., Conclusions: Fasting C-peptide at type 2 diabetes diagnosis is an independent risk factor for total and cancer-related mortality. Thus, treatment of type 2 diabetes should focus not only on normalising blood glucose levels but also on mitigating insulin resistance., (© 2021 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background The accumulation of myocardial triglycerides and remodeling of the left ventricle are common features in type 2 diabetes mellitus and represent potential risk factors for the development of diastolic and systolic dysfunction. A few studies have investigated the separate effects of diet and exercise training on cardiac function, but none have investigated myocardial changes in response to a combined diet and exercise intervention. This 12-week randomized study assessed the effects of a Paleolithic diet, with and without additional supervised exercise training, on cardiac fat, structure, and function. Methods and Results Twenty-two overweight and obese subjects with type 2 diabetes mellitus were randomized to either a Paleolithic diet and standard-care exercise recommendations ( PD ) or to a Paleolithic diet plus supervised exercise training 3 hours per week ( PD - EX ). This study includes secondary end points related to cardiac structure and function, ie, myocardial triglycerides levels, cardiac morphology, and strain were measured using cardiovascular magnetic resonance, including proton spectroscopy, at baseline and after 12 weeks. Both groups showed major favorable metabolic changes. The PD - EX group showed significant decreases in myocardial triglycerides levels (-45%, P=0.038) and left ventricle mass to end-diastolic volume ratio (-13%, P=0.008) while the left ventricle end-diastolic volume and stroke volume increased significantly (+14%, P=0.004 and +17%, P=0.008, respectively). These variables were unchanged in the PD group. Conclusions Exercise training plus a Paleolithic diet reduced myocardial triglycerides levels and improved left ventricle remodeling in overweight/obese subjects with type 2 diabetes mellitus. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01513798.

Background: Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed., Methods: Thirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX)., Results: For the within group analyses, fat mass decreased by 5.7 kg (IQR: -6.6, -4.1; p < 0.001) in the PD group and by 6.7 kg (-8.2, -5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA 1c decreased by 0.9% (-1.2, -0.6; p < 0.001) in the PD group and 1.1% (-1.7, -0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (-3.6, -1.3) in the PD group and by 1.2 kg (-1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups)., Conclusions: A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

The existence of adult haemangioblasts with dual haematopoietic and endothelial developmental potential was confirmed after detection of Ph(+) vascular endothelial cells in chronic myeloid leukaemia (CML) patients. Blood outgrowth endothelial cells (OECs) from CML patients were found not to harbour the Philadelphia translocation and were thus not clonally related to BRC/ABL1(+) hematopoietic progenitors, but comprised a distinct subfraction of endothelial cells. Remarkably, the frequency of CML-derived OECs was 9-fold higher as compared to healthy donors (n = 19 and n = 300, respectively; P < 0.0001) and these cells showed increased proliferative potential, possibly reflecting the mobilisation of OEC progenitors by pro-angiogenic cytokines.

Autoimmune lymphoproliferative syndrome (ALPS) is a paediatric disease characterized by lymphoproliferation and autoimmunity. Most patients are known to carry heterozygous mutations of the TNFRSF6 gene leading to diminished Fas-mediated apoptosis and failure of activated lymphocytes to undergo apoptosis. A subgroup of patients without the TNFRSF6 gene mutation has similar defective apoptosis and clinical features. No effective treatment has been reported so far. Glucocorticoids, intravenous immunoglobulin and/or immunosuppressive drugs have usually led to only transient clinical improvement. Seven ALPS patients (two type Ia and five type III) were treated with the antimalarial drug Fansidar. No toxicity was observed. An objective response was seen in six of them and, in two, the treatment was stopped without reappearance of the symptoms. Moreover, a marked decrease in interleukin-10 levels was observed in two patients during the treatment. We found that the drug induced apoptosis in activated lymphocytes through activation of the mitochondrial apoptotic pathway.

Fas is a protein that plays a major role in the apoptotic mechanism of several cell types, including white blood cells (WBC). Mutations of the Fas gene in humans are known to lead to autoimmune lymphoproliferative syndrome (ALPS). Glucocorticoids or cytostatic drugs are sometimes used to treat the lymphoproliferation in these patients. When treated with the anti-malaria drug Fansidar, a patient with ALPS showed a marked shrinkage of the lymph node masses, decrease in peripheral blood lymphocytes (PBL) and an increase in neutrophil numbers. In addition, an increased Fas expression was seen on all types of leucocytes.

Renal function was evaluated in 12 children (aged 2.5-17.5 years) who received ifosfamide as part of their chemotherapy for different malignancies. A blood and urine analysis evaluating renal glomerular and tubular function and an isotopic determination of glomerular filtration were carried out four months or later after treatment had been stopped. Three patients had several biochemical abnormalities suggesting a significant degree of proximal renal dysfunction (increased urinary excretion of calcium, glucose, beta 2-microglobulin, amino acids (three patients) and decreased tubular reabsorption of phosphate (one patient)). The tubular dysfunction in these patients was associated with a diminished glomerular filtration. These patients could be characterized by their younger age at treatment and a higher dose of ifosfamide received if calculated per kg body weight.