Dynamic modulation of emotional processing

Recent findings suggest the processing of emotional stimuli is prioritized compared to neutral stimuli; however, it is not necessarily automatic and depends on several modulating factors. The current paper highlights three major factors that affect the reactions to emotional stimuli: (i) stimulus properties, (ii) task demands and attention, and (iii) individual characteristics. The evidence reviewed here suggests that individual characteristics shape the structure, function and connectivity within a neural network that is involved in the reactions to emotional stimuli. This neural network includes regions related to emotion and attention, in line with evidence for reciprocal connections between these two processes. Activation in this network further depends on the emotional value of a certain item, as well as physical features of the stimulus. This integrative view can lead to better understanding of the underlying mechanisms of emotional reactions, as well as better therapeutic approaches.     

Timing abilities among children with developmental coordination disorders (DCD) in comparison to children with typical development

Timing ability is essential for common everyday performance. The aim of the study was to compare timing abilities and temporal aspects of handwriting performance and relationships between these two components among children with Developmental Coordination Disorders (DCD) and a control group. Forty two children, 21 diagnosed as DCD and 21 with typical development, aged 7–12, were matched for age, gender and school performed 14 tasks of the interactive metronome (IM) and three functional handwriting tasks on an electronic tablet that was part of a computerized system (ComPET – computerized penmanship evaluation tool). The IM supplies response time, while on-paper and in-air time per written stroke is received from the ComPET. Results indicated significant differences between the groups for both IM and handwriting tasks (ComPET). Linear regression indicated that the mean IM response time explained 37% of variance of the in-air time per stroke during a paragraph-copying task. Furthermore, based on one discriminate function including two measures reflected timing ability, 81% of all participants were correctly classified into groups. Study results strongly recommend consideration of the IM as an evaluation and intervention tool for children with DCD who are faced with timing deficits in their everyday functioning.     

The road not taken: Social vs. private comparisons in Asperger׳s syndrome and high functioning autism

Evaluation of the outcomes of our decisions may instigate comparisons of our actual outcome with those of others (social comparisons) or comparisons with alternative outcomes of choices not made (private comparisons). Previous research has suggested a deficit in attention to social information among individuals with autism spectrum disorders. As social comparison involves the processing of social information, here we investigated the orientation towards and sensitivity to social vs. private comparisons in individuals with autism spectrum disorders. We compared the sensitivity to social vs. private comparisons among individuals diagnosed with Asperger’s Syndrome (AS) or High Functioning Autism, using a task that entailed monetary rewards. Results showed that while individuals with AS generally demonstrate comparable sensitivity to absolute and relative rewards, they show less sensitivity to social comparison as compared to controls. Furthermore, they are characterized by a higher sensitivity to private rather than social comparison. These results suggest that low sensitivity to social comparisons is an important factor to consider in autism spectrum disorders.     

Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning

Reduced‐toxicity conditioning with fludarabine and treosulfan is a dose‐intensive regimen with enhanced anti‐leukemia effect and acceptable toxicity in AML/MDS. HLA‐C regulates natural‐killer (NK) cell function by inhibiting Killer immunoglobulin‐like receptors (KIR) and is divided into C1 and C2 epitopes. The missing‐ligand theory suggests that missing recipient KIR ligands drives NK‐alloreactivity after SCT, in the absence of HLA‐mismatch by activating unlicensed donor NK cells. We analyzed SCT outcomes in 203 patients with AML/MDS, median age 58 years, given SCT from matched‐siblings (n = 97) or matched‐unrelated donors (n = 106), using two treosulfan doses (total 36 or 42 g/m²). 34% expressed one HLA‐C group 1 allele (C1C1), 19% one HLA‐C group 2 allele (C2C2), and 48% both KIR ligands (C1C2). Median follow‐up was 48 months. 5‐year relapse, nonrelapse mortality (NRM) and leukemia‐free survival (LFS) rates were 38%, 27%, and 36%, respectively. Relapse rates were 43%, 45%, and 26% in patients expressing C1C1, C1C2, and C2C2 ligands, respectively (P = .03). Multivariate‐analysis identified chemo‐refractory disease (HR 3.1, P = .003), poor cytogenetics (HR 1.7, P = .08), female donor to male recipient (HR 0.4, P = .01) and C2C2 ligands (HR 0.4, P = .04) as independent factors predicting relapse. HLA‐C ligands were not associated with GVHD or NRM. LFS was 33%, 30%, and 46%, respectively (P = .07). Chemorefractory disease (HR 3.1, P = .0004) and C2C2 group ligand (HR 0.6, P = .06) independently predicted LFS. Treosulfan dose did not predict any SCT outcome. In conclusion, missing HLA‐C group 1 ligand is associated with reduced relapse risk, similar NRM and improved LFS, after HLA‐matched SCT with treosulfan conditioning in AML/MDS.     

The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24⁻ stem cell-like breast cancer cells in human tumors

Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 cell populations in human breast tumors with distinct properties: CD44+CD24- cells that have stem cell-like characteristics, and CD44-CD24+ cells that resemble more differentiated breast cancer cells. Here we identified 15 genes required for cell growth or proliferation in CD44+CD24- human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts. Our results highlight the differences between distinct breast cancer cell types and identify targets such as JAK2 and Stat3 that may lead to more specific and effective breast cancer therapies.     

Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region

The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.     

Antidepressants reverse short-photoperiod-induced, forced swim test depression-like behavior in the diurnal fat sand rat: further support for the utilization of diurnal rodents for modeling affective disorders

Recent findings demonstrate strong links between abnormalities in circadian rhythms and sleep and the etiology, pathophysiology and treatment of major affective disorders. Further exploration of these interactions requires the development, identification and utilization of good and predictive animal models. The biology and behavior related to circadian rhythms are significantly different in diurnal and nocturnal rodents. Accordingly, it is possible that exploring the interactions between these mechanisms and affective change in diurnal animals may be advantageous. Recent studies demonstrate that diurnal fat sand rats and Nile grass rats show depression-like behavior when maintained under short-photoperiod (SP) conditions compared with animals maintained under neutral photoperiod (NP) conditions. Moreover, these behaviors were ameliorated after treatment with bright light. The present study further explores the possible utility of sand rats as animal models by testing the effects of antidepressants on the SP-induced depression-like behaviors of sand rats. Sand rats maintained in SP or NP conditions for 3 weeks were treated subchronically (5 injections) with the clinically effective antidepressant bupropion, and their behavior was tested in a number of depression-related tests. Results show that antidepressant treatment reverses the effects of SP conditions in the forced swim test, but that neither SP conditions nor antidepressants influenced sweet solution preference. These results partly support the validity of the sand rat model, but suggest that not all tests that were validated in nocturnal laboratory rodents can be applied to other rodent species and that additional tests should be applied to further explore the validity of the model.     

Intussusception in children in Southern Israel: disparity between 2 populations

BACKGROUND: Intussusception has been associated with 1 rotavirus vaccine. Our objective was to determine intussusception rates in children in southern Israel during a 15-year period before the introduction of new rotavirus vaccines. METHODS: All children born at the Soroka Medical Center are hospitalized in that center, enabling population-based studies. Two populations reside in Southern Israel: the Jewish population (comparable to a Western population) and the Bedouin population (comparable to a developing population). Retrospectively, all children <5 years of age admitted with ICD-9 code for intussusception were recorded as well as their demographic and clinical data. RESULTS: During 1990-2004, 316 patients with intussusception [241 (76%) Jewish children and 75 (24%) Bedouin children] were recorded. None died. The mean annual rates for children <5 years (per 100,000) were 49.3 +/- 17.4 and 18.9 +/- 9.6 for Jewish and Bedouin children, respectively (P < 0.001), with a significant increase in intussusception rates during the study period in Bedouin (P = 0.022), but not in Jewish children (P = 0.38). Mean annual intussusception rates per 100,000 for children <12 months were 199.6 +/- 5.2 and 66.8 +/- 44.1 for Jews and Bedouin infants, respectively (P < 0.001). In Bedouin children, a significantly higher number of cases were observed from March to May, whereas no seasonality pattern was noted in Jewish children. Negative correlation between intussusception and gastroenteritis was found in Bedouin infants during the summer months, whereas no such correlation was found in Jewish infants. CONCLUSIONS: Pre-rotavirus vaccination intussusception rate is high especially among Jewish infants in Southern Israel. Intussusception rates increased significantly during the study period in Bedouin infants.     

New reproductive technologies, genetic counselling and the standing of the fetus: views from Germany and Israel

This paper reports findings from a comparative study of Israeli and German genetic counsellors' perceptions of the moral standing of the fetus. Data collected through in-depth interviews with counsellors in both countries (N=32) are presented, and their moral practices are analysed. The paper's findings suggest that while German counsellors perceive the fetus as an autonomous being and debate the particular biological stages through which this autonomy is acquired; Israeli counsellors do not consider the moral status of the fetus independently of its relations with its family hence, deploying a 'relational ethics'. It is suggested that these differences are influenced by historical, political, legal, and religious traditions in Germany and Israel regarding abortions and the fetus. It is concluded that the deployment of a 'biological ethics' by German counsellors reproduces the model of fetal developmental stages (in itself a construction), and hence goes hand in hand with perceptions of the fetus as a 'life', and thus as the bearer of autonomous rights which are understood to contradict those of its mother. On the other hand, the rejection of 'biological ethics' by Israeli counsellors enables a perception of fetuses that is first and foremost defined by their relationships with others.