Deletion 18q21.2q21.32 involving TCF4 in a boy diagnosed by CGH-array

We report on a 12 year-old boy presenting with severe developmental delay, dysmorphic features, limb anomalies, growth retardation, hypoplastic vermis and corpus callosum. Conventional and high-resolution cytogenetic analyses were normal. CGH-array allowed characterisation of a de novo 6.2 Mb 18q21.2q21.32 interstitial deletion involving TCF4, the recently identified gene responsible for Pitt-Hopkins syndrome (PHS). No tachypnoea-apnoea paroxysms were observed. We discuss the dysmorphic features particularly involving the ears, which might be helpful towards PHS and 18q21 deletion diagnosis.     

A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population

Sepsis describes a complex clinical syndrome resulting from a systemic inflammatory response to bacteria. Functional studies in animal models of sepsis have catalogued CXCL2 as a candidate gene for the development of the disease. We hypothesized that CXCL2 polymorphisms may confer susceptibility to sepsis and performed an association study using 178 severe sepsis patients and 357 population-based controls. We selected two polymorphisms from the promoter of the gene (-437A/G and -665(AC)n), and analyzed whether haplotypes or single loci were associated with disease susceptibility. An overall test of differentiation showed that haplotype distribution was not different between cases and controls (P=0.407). Likewise, -437A/G was not associated with disease susceptibility (heterozygote odds ratio (OR) 0.68 (0.47-1.03), and homozygote OR 0.86 (0.56-1.32); P=0.706). However, for the -665(AC)n, we found that the 24+/-1 repeat alleles were associated with susceptibility (heterozygote OR 2.82 (1.10-7.24), and homozygote OR 3.65 (1.41-9.43); P=0.0006). This association remained significant when using a multiple logistic regression analysis (OR 2.23; 95% confidence intervals (95% CI) 1.22-4.03; P=0.008) and after a genomic control adjustment (P=0.017). Although replicate studies and functional assays are needed, these results suggest that CXCL2 gene variants may contribute to the development of severe sepsis.     

Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses

Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long-term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post-mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following brain injury, potentially leading to significant brain dysfunction. However, such alterations have never been investigated in the context of juvenile mTBI (jmTBI). A closed-head injury model was used to study jmTBI on postnatal-day 17 mice. Astrogliosis was evaluated using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days postinjury (dpi). In vivo T2-weighted-imaging (T2WI) and diffusion tensor imaging (DTI) were performed at 7 and 30 dpi to examine tissue level structural alterations. Increased GFAP-labeling was observed up to 30 dpi in the ipsilateral SSC, the initial site of the impact. However, vimentin and nestin expression was not perturbed by jmTBI. The morphology of GFAP positive cells was significantly altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with magnetic resonance imaging changes. T2WI and DTI values were significantly altered at 30 dpi within these brain regions most prominently in regions distant from the impact site. Our data show that jmTBI triggers changes in astrocytic phenotype with a distinct spatiotemporal pattern. We speculate that the presence and time course of astrogliosis may contribute to pathophysiological processes and long-term structural alterations following jmTBI.     

Factors That Influence the Appearance of Central Nervous System Leukemia

At present, central nervous system (CNS)leukemia is one of the principal causes fortermination of complete remission in acutelymphocytic leukemia (ALL). The factorswhich influence the increase of CNS infiltration have been studied comparingdifferent parameters (age, initial peripheral WBC count, type of leukemia, andpresence or absence of initial organomegaly) to determine the leukemia populationwith highest risk of developing this syndrome. A total of 127 cases of acutelymphoid leukemia (ALL) (98 children and29 adults) and 101 acute myelocytic leukemia (AML) (41 children and 60 adults),on the same treatment protocol from 1967to 1970, were included in this study. Themedian survival and the rate of incidenceof symptomatic CNS leukemia was 18 moand 32% in ALL and 4 mo and 7% in AML.The incidence of CNS leukemia per monthof survival was similar in both groups:4 mo, 3% in AML and 4% in ALL, at 8 mo,13% in both ALL and AML. The incidenceof CNS leukemia was higher in childrenwith ALL than in adults: 41% in childrenand 19% in adults at 20-mo survival.Organomegaly (spleen, liver and/orlymph nodes) as an early manifestationincreased the risk of CNS involvement. TheCNS infiltration was significantly greaterin patients with high initial peripheralWBC count. The incidence of meningealleukemia did not differ in ALL and AML. Inconclusion, CNS leukemia infiltration wasmore frequent in children with initialorganomegaly and high WBC count at thetime of diagnosis.

Submitted on November 8, 1972 Revised on January 29, 1973 Accepted on February 28, 1973     

Evidence of association of KIBRA genotype with episodic memory in families of psychotic patients and controls

The first genome-wide association study of human memory identified an association between a common T/C polymorphism of the KIBRA gene (rs17070145) and episodic memory performance in normal individuals; subsequent studies have implicated the same polymorphism in Alzheimer’s disease. Since impaired neurocognitive performance, including memory, may be both a core feature of schizophrenia and a candidate endophenotype, we attempted to replicate this association in a total sample of 544 subjects (including patients with psychosis, their unaffected relatives as well as normal individuals). In the combined sample there was a significant association between the KIBRA T allele and better performance in the single principle component of the memory measures, which included immediate and delayed logical and visual memory from the Wechsler Memory Scale (p = 0.019). In the unaffected individuals (patients’ relatives and healthy controls) we observed an association of KIBRA with immediate and delayed logical memory (p = 0.020 and 0.025, respectively), while in patients with psychosis with delayed visual memory (p = 0.05). This study replicates the association between the KIBRA gene and episodic memory and suggests a possibly differential effect of the polymorphism in psychotic and non-psychotic individuals.     

Pre-orthographic character string processing and parietal cortex: A role for visual attention in reading?

The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of character type. While the superior parietal lobule has been shown to be involved in multiple letter processing, further data is necessary to extend these results to non-letter characters. The purpose of this study is to identify the neural correlates of pre-orthographic character string processing independently of character type. Fourteen skilled adult readers carried out multiple and single element visual categorization tasks with alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of parietal cortex in multiple element processing was further probed with a priori defined anatomical regions of interest (ROIs). Participants activated posterior parietal cortex more strongly for multiple than single element processing. ROI analyses showed that bilateral SPL/BA7 was more strongly activated for multiple than single element processing, regardless of character type. In contrast, no multiple element specific activity was found in inferior parietal lobules. These results suggests that parietal mechanisms are involved in pre-orthographic character string processing. We argue that in general, attentional mechanisms are involved in visual word recognition, as an early step of word visual analysis.     

A transdiagnostic comparison of trauma and panic memories in PTSD, panic disorder, and healthy controls

Inadequate processing of trauma information is considered to lead to particularly vivid recollections and disorganized memories of the trauma. Although trauma memories have mainly been investigated in PTSD, memories in other psychiatric disorders may actually share some characteristics. This may particularly be true for patients with panic disorder with agoraphobia (PDA) as a first panic attack resembles trauma. To test this hypothesis, PTSD trauma memories (n = 59) were compared with PDA panic memories (n = 58), and trauma memories of healthy trauma victims (n = 135) on self-reported re-experiencing and disorganization. PTSD trauma memories had more re-experiencing elements than memories of the other two groups, although PDA memories had more re-experiencing elements than the controls' trauma memories. Relative to the controls, PTSD and PDA memories were disorganized. Peritraumatic dissociation and current memory-associated dissociation were also high in PTSD and PDA patients compared to the controls. Implications of these results are discussed.     

Role of MDCT in identification of the bleeding site and the vessels causing hemoptysis

OBJECTIVE: MDCT has improved the management of hemoptysis by providing more precise depiction of bronchial and nonbronchial systemic arteries than conventional CT. The purpose of this article is to review the role of MDCT in the identification of the bleeding site and the vessels causing hemoptysis. CONCLUSION: Identification of the origin of the involved systemic arteries (bronchial and nonbronchial) or involved pulmonary artery on MDCT enables the interventional radiologist to treat them, especially in elderly patients with a tortuous aorta and atheroma.