Age-dependent changes in the neural substrates of empathy in autism spectrum disorder

In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12–31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face’s emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the ‘fine-tuning’ of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms.     

Standardized Ultrasound Measurement of Subcutaneous Fat Patterning: High Reliability and Accuracy in Groups Ranging from Lean to Obese

A recently standardized ultrasound technique for measuring subcutaneous adipose tissue (SAT) was applied to normal-weight, overweight and obese persons. Eight measurement sites were used: upper abdomen, lower abdomen, erector spinae, distal triceps, brachioradialis, lateral thigh, front thigh and medial calf. Fat compression was avoided. Fat patterning in 38 participants (body mass index: 18.6–40.3 kgm^?2; SAT thickness sums from eight sites: 12–245 mm) was evaluated using a software specifically designed for semi-automatic multiple thickness measurements in SAT (sound speed: 1450 m/s) that also quantifies embedded fibrous structures. With respect to ultrasound intra-observer results, the correlation coefficient ρ = 0.999 (p < 0.01), standard error of the estimate = 1.1 mm and 95% of measurements were within ±2.2 mm. For the normal-weight subgroup, the median measurement deviation was 0.43 mm (1.1% of mean thickness), and for the obese/overweight subgroup it was 0.89 mm (0.5%). The eight sites used here are suggested to represent inter-individual differences in SAT patterning. High measurement accuracy and reliability can be obtained in all groups, from lean to overweight and obese, provided that measurers are trained appropriately.     

Assessment of Left Ventricular Size and Function during Cardiac Surgery. An Intraoperative Evaluation of Six Two‐Dimensional Echocardiographic Methods with Real Time Three‐Dimensional Echocardiography as a Reference

Transesophageal echocardiography is recommended to monitor left ventricular (LV) size and function in various operations. Generally, two‐dimensional (2D) methods are applied intraoperatively. The aim of this study was to compare the accuracy and feasibility of 6 commonly used 2D methods to assess LV function during surgery. LV function in 120 consecutive patients was evaluated. Real time three‐dimensional transesophageal echocardiograpy (3DTEE) served as reference. End‐diastolic and end‐systolic volumes and ejection fraction (EF) were analyzed with Simpson's method of discs (monoplane [MP] and biplane [BP]), eyeball method, Teichholz' method, and speckle tracking (ST) methods. Furthermore, fractional area change (FAC) and peak systolic pressure rise (dP/dt) were determined. Each 2D method was evaluated regarding correlation and agreement with 3DE, intra‐ and interobserver variability and the time required for evaluation. Simpson BP showed the strongest correlation and best agreement with 3DE for EF (limits of agreement 3.7 ± 11.6%) and volumes. Simpson MP showed similar agreement with 3DE compared to ST (2.8 ± 14.5% vs. 2.0 ± 15.3% and 3.8 ± 14.4% vs. 1.9 ± 15.6%, respectively). Both the eyeball method and Teichholz' method showed wide limits of agreement (?1.5 ± 18.2% and 5.2 ± 22.1%, respectively). DP/dt did not correlate with 3DE. FAC and ST FAC showed similar agreement. Application of 3DE (429 ± 108 seconds) took the longest time, and the eyeball method took the shortest time (8 ± 5 seconds) for analysis. Simpson BP is the most accurate intraoperative 2D method to evaluate LV function, followed by long‐axis MP evaluations. Short‐axis views were less accurate but may be suited for monitoring. We do not recommend using dP/dt.     

Distribution of Oxytocin‐ and Vasopressin‐Immunoreactive Neurons in the Brain of the Eusocial Mole Rat (Fukomys anselli)

Fukomys anselli, also known as Ansell's mole rat, is a subterranean, highly social (so‐called eusocial) rodent that lives in Africa. These mole rats typically form multigenerational families consisting of a single monogamous breeding pair and their nonreproductive offspring. Research on other mammals suggests that oxytocin (OT) and vasopressin (VP) as well as the distribution of OT‐ and VP‐receptors may influence social behavior and pair bonding. Recent studies on eusocial naked mole rats have shown a possible relation between sociality and OT‐immunoreactive (OT‐ir) processes. In this study, we examined expression patterns of OT and VP in the brains of F. anselli and the common Sprague‐Dawley (SD) laboratory rat. As in other species, the majority of OT‐ir and VP‐ir neurons was found in the paraventricular (Pa) and supraoptic (SO) nuclei, and scattered labeling throughout the preoptic and anterior hypothalamic areas. We found no difference in either quality or quantity of OT‐ and VP‐ir neurons between individuals of different social and reproductive ranks. Equally unexpected was the finding of specific OT‐immunoreactivity in neurons of the mammillary complex of F. anselli that was not found in SD rats. Further studies are needed to determine whether these mammillary OT‐ir neurons are causally related to monogamy in F. anselli and whether these correlates of monogamy are found in other species. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Energy density,diet quality,and central body fat in a nationwide survey of young Spaniards

ObjectivesTo determine the impact of energy density on diet quality and anthropometric proxy measures for central body fat in young Spaniards.MethodsData were obtained from a representative national sample of 2513 young Spaniards aged 10 to 24 y. Dietary assessment was performed with a 24-h recall. Adherence to the Mediterranean diet was measured by the KIDMED index. Reduced rank regression analysis was used to identify energy-density dietary patterns. Waist circumferences and height were measured.ResultsPastries and sausages showed the strongest loading for the dietary energy density factor score (DED-FS), with fruits and vegetables at the opposite end of the scale. Multiple linear regression analysis showed a positive association (P < 0.01) of dietary energy density (DED) and the DED-FS with waist circumferences regressed on height and age (WC_height+age) and waist-to-height ratio (WHtR). The adjusted odds ratio for elevated WC_height+age and WHtR increased across quartile distribution of DED (P < 0.001) and DED-FS (P < 0.05). Diet quality characterized by the KIDMED index was negatively associated (P < 0.001) with DED and the DED-FS.ConclusionsHigher DED is a risk for increased central fat distribution and is associated with low adherence to the Mediterranean diet.     

Antibody mediated CDCP1 degradation as mode of action for cancer targeted therapy

CUB-domain-containing-protein-1 (CDCP1) is an integral membrane protein whose expression is up-regulated in various cancer types. Although high CDCP1 expression has been correlated with poor prognosis in lung, breast, pancreas, and renal cancer, its functional role in tumor formation or progression is incompletely understood. So far it has remained unclear, whether CDCP1 is a useful target for antibody therapy of cancer and what could be a desired mode of action for a therapeutically useful antibody. To shed light on these questions, we have investigated the cellular effects of a therapeutic antibody candidate (RG7287). In focus formation assays, prolonged RG7287 treatment prevented the loss of contact inhibition caused by co-transformation of NIH3T3 cells with CDCP1 and Src. In a xenograft study, MCF7 cells stably overexpressing CDCP1 reached the predefined tumor volume faster than the parental MCF7 cells lacking endogenous CDCP1. This tumor growth advantage was abolished by RG7287 treatment. In vitro, RG7287 induced rapid tyrosine phosphorylation of CDCP1 by Src, which was accompanied by translocation of CDCP1 to a Triton X-100 insoluble fraction of the plasma membrane. Triggering these effects required bivalency of the antibody suggesting that it involves CDCP1 dimerization or clustering. However, this initial activation of CDCP1 was only transient and prolonged RG7287 treatment induced internalization and down-regulation of CDCP1 in different cancer cell lines. Antibody stimulated CDCP1 degradation required Src activity and was proteasome dependent. Also in three different xenograft models with endogenous CDCP1 expression RG7287 treatment resulted in significant tumor growth inhibition concomitant with substantially reduced CDCP1 levels as judged by immunohistochemistry and Western blotting. Thus, despite transiently activating CDCP1 signaling, the RG7287 antibody has a therapeutically useful mode of action.     

Comparative evaluation of a heparin‐citrate anticoagulation for LDL‐apheresis in two primary apheresis systems

BACKGROUND: As COBE Spectra has been replaced in many parts of the world, we describe a new protocol for low‐density lipoprotein (LDL)‐apheresis performed on familial hypercholesterolemia patients for the Spectra Optia platform. METHODS: For all procedures, after administering a bolus of heparin of 2,500 U, 10,000 U of heparin added to a 600 ml ACD‐A bag was used as anticoagulant (AC). In a first phase (A), 16 apheresis procedures with COBE Spectra using an inlet:AC ratio of 25:1 were compared to 18 LDL‐apheresis treatments with Spectra Optia at split Inlet:AC ratios of 16:1/18:1 or 20:1/25:1. Platelet activation and coagulation markers were assessed. In a follow‐up phase (B), 20 procedures on Spectra Optia using an inlet:AC ratio of 20:1 were performed. RESULTS: Although coagulation markers and platelet activation analyzed were similar in both apheresis devices used, COBE Spectra procedures did not show any visual clumping in the sets. Visual analysis of clumping was highest in the Spectra Optia's 20:1/25:1 AC regimen (5/8 procedures). For the lowest Spectra Optia, AC regimen and during the follow‐up phase reversible clump formation in the disposable set was similar (1/10 procedures). Clumping was successfully reversed in all cases by temporarily lowering the inlet:AC ratio to 18:1. Blood cell counts (WBC, Plt, Hct) were similar for both COBE Spectra and Spectra Optia procedures. Spectra Optia had a significantly higher plasma removal efficiency versus COBE Spectra (84% vs.75%, P < .05). No serious adverse events were observed. CONCLUSION: Apheresis procedures on the Spectra Optia system with low‐dose heparin‐citrate anticoagulation are feasible and safe.     

Commentary on “Possible induction of acute disseminated encephalomyelitis (ADEM)-like demyelinating illness by intrathecal mesenchymal stem cell injection”

The case report that is the subject of this Commentary describes a 27-year-old woman, who, 3 months after a devastating low cervical myelitis, underwent intrathecal mesenchymal stem cell (MSC) infusions. Six hours after the third infusion, she became unconscious, febrile and cerebral MRI showed acute bitemporal and left cerebellar lesions, consistent with an acute disseminated encephalomyelitis. It is likely that this is the first reported patient with neuroinflammatory exacerbation after MSC therapy. This case suggests that, in addition to their malignant potential, autologous MSC expanded in vitro can exhibit immune-activating properties leading to autoimmune exacerbation.     

Architectural switch in plant photosynthetic membranes induced by light stress

Unavoidable side reactions of photosynthetic energy conversion can damage the water-splitting photosystem II (PSII) holocomplex embedded in the thylakoid membrane system inside chloroplasts. Plant survival is crucially dependent on an efficient molecular repair of damaged PSII realized by a multistep repair cycle. The PSII repair cycle requires a brisk lateral protein traffic between stacked grana thylakoids and unstacked stroma lamellae that is challenged by the tight stacking and low protein mobility in grana. We demonstrated that high light stress induced two main structural changes that work synergistically to improve the accessibility between damaged PSII in grana and its repair machinery in stroma lamellae: lateral shrinkage of grana diameter and increased protein mobility in grana thylakoids. It follows that high light stress triggers an architectural switch of the thylakoid network that is advantageous for swift protein repair. Studies of the thylakoid kinase mutant stn8 and the double mutant stn7/8 demonstrate the central role of protein phosphorylation for the structural alterations. These findings are based on the elaboration of mathematical tools for analyzing confocal laser-scanning microscopic images to study changes in the sophisticated thylakoid architecture in intact protoplasts.