Ventricular but not atrial electro-mechanical delay of the embryonic heart is altered by anoxia-reoxygenation and improved by nitric oxide.

BACKGROUND/AIM: Excitation-contraction coupling is modulated by nitric oxide (NO) which otherwise has either beneficial or detrimental effects on myocardial function during hypoxia-reoxygenation. This work aimed at characterizing the variations of electromechanical delay (EMD) induced by anoxia-reoxygenation within the developing heart and determining whether atrial and ventricular EMD are modulated by NO to the same extent. METHODS: Hearts of 4 or 4.5-day-old chick embryos were excised and submitted in vitro to normoxia (45 min), anoxia (30 min) and reoxygenation (60 min). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout experiment. Anoxia-reoxygenation-induced chrono-, dromo-and inotropic disturbances and changes in EMD in atrium (EMDa) and ventricle (EMDv) were investigated in control hearts and in hearts exposed to 0.1, 1, 10, 50 and 100 microM of DETA-NONOate (a NO donating agent) or to 50 microM of L-NAME (a NOS inhibitor). RESULTS: Under normoxia, heart rate, PR interval, ventricular shortening velocity, EMDa and EMDv were similar in control, L-NAME-treated and DETA-NONOate-treated hearts. Under anoxia, cardiac activity became markedly erratic within less than 10 min in all groups. At the onset of reoxygenation, EMDv was increased by about 300% with respect to the preanoxic value while EMDa did not vary significatively. Compared to control conditions, L-NAME or DETA-NONOate had no influence on the negative chrono-, dromo- and inotropic effects induced by anoxia-reoxygenation. However, L-NAME prolonged EMDv during anoxia and delayed EMDv recovery during reoxygenation while 100 microM DETA-NONOate had the opposite effects. EMDa was neither affected by NOS inhibitor nor NO donor. At the end of reoxygenation, all the investigated parameters returned to their basal values. CONCLUSION: This work provides evidence that a NO-dependent pathway is involved in regulation of the ventricular excitation-contraction coupling in the anoxic-reoxygenated developing heart.

Branstad Inaugural speech, January 14, 2011

Inaugural speech by Governor Terry Branstad

Ventral and dorsal pathways of speech perception: An intracerebral ERP study.

Recent theory of physiology of language suggests a dual stream dorsal/ventral organization of speech perception. Using intra-cerebral Event-related potentials (ERPs) during pre-surgical assessment of twelve drug-resistant epileptic patients, we aimed to single out electrophysiological patterns during both lexical-semantic and phonological monitoring tasks involving ventral and dorsal regions respectively. Phonological information processing predominantly occurred in the left supra-marginal gyrus (dorsal stream) and lexico-semantic information occurred in anterior/middle temporal and fusiform gyri (ventral stream). Similar latencies were identified in response to phonological and lexico-semantic tasks, suggesting parallel processing. Typical ERP components were strongly left lateralized since no evoked responses were recorded in homologous right structures. Finally, ERP patterns suggested the inferior frontal gyrus as the likely final common pathway of both dorsal and ventral streams. These results brought out detailed evidence of the spatial-temporal information processing in the dual pathways involved in speech perception.

Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay.

The bleeding disorder Bernard-Soulier syndrome (BSS) is caused by mutations in the genes coding for the platelet glycoprotein GPIb/IX receptor. The septin SEPT5 is important for active membrane movement such as vesicle trafficking and exocytosis in non-dividing cells (i.e. platelets, neurons). We report on a four-year-old boy with a homozygous deletion comprising not only glycoprotein Ibβ (GP1BB) but also the SEPT5 gene, located 5' to GP1BB. He presented with BSS, cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect. The homozygous deletion of GP1BB and SEPT5, which had been identified by PCR analyses, was confirmed by Southern analyses and denaturing HPLC (DHPLC). The parents were heterozygous for this deletion. Absence of GPIbβ and SEPT5 proteins in the patient's platelets was illustrated using transmission electron microscopy. Besides decreased GPIb/IX expression, flow cytometry analyses revealed impaired platelet granule secretion. Because the bleeding disorder was extremely severe, the boy received bone marrow transplantation (BMT) from a HLA-identical unrelated donor. After successful engraftment of BMT, he had no more bleeding episodes. Interestingly, also his mental development improved strikingly after BMT. This report describes for the first time a patient with SEPT5 deficiency presenting with cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner.

BACKGROUND & AIMS: Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS: We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS: The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS: The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

Stochastic delay equations with non-negativity constraints driven by fractional Brownian motion

In this note we prove an existence and uniqueness result for the solution of multidimensional stochastic delay differential equations with normal reflection. The equations are driven by a fractional Brownian motion with Hurst parameter H > 1/2. The stochastic integral with respect to the fractional Brownian motion is a pathwise Riemann¿Stieltjes integral.

Stochastic delay differential equations driven by fractional Brownian motion with Hurst parameter H 1/2

We consider the Cauchy problem for a stochastic delay differential equation driven by a fractional Brownian motion with Hurst parameter H>¿. We prove an existence and uniqueness result for this problem, when the coefficients are sufficiently regular. Furthermore, if the diffusion coefficient is bounded away from zero and the coefficients are smooth functions with bounded derivatives of all orders, we prove that the law of the solution admits a smooth density with respect to Lebesgue measure on R.

Sign language in Landau-Kleffner syndrome.

This article reviews the history of sign language (SL) and the rationale for its use in children with profound auditory agnosia due to Landau-Kleffner syndrome (LKS), illustrated by studies of children and adults followed for many years and rare cases from the literature. The reasons that SL was successful and brought some children out of isolation while it could not be implemented in others are discussed. The nowadays earlier recognition and treatment of LKS and better awareness of the crucial need to maintain communication have certainly improved the outcome of affected children. Alternatives to oral language, even for less severe cases, are increasingly accepted. SL can be learned at different ages with a clear benefit, but the ambivalence of the patients and their families with the world and culture of the deaf may sometimes explain its refusal or limited acceptance. There are no data to support the fear that SL learning may delay or prevent oral language recovery in children with LKS. On the contrary, SL may even facilitate this recovery by stimulating functionally connected core language networks and by helping speech therapy and auditory training.

Vitamin D deficiency: A forgotten treatable cause of motor delay and proximal myopathy.

We report a four-year-old African boy referred for proximal muscle weakness, fatigability and episodic limb pain. Classical causes of structural and metabolic myopathy were initially considered before clinical and biological features of vitamin D deficiency rickets were identified. Prompt treatment with vitamin D and calcium supplementation led to a complete reversal of the muscle symptoms. Rickets-associated myopathy should be included in the differential diagnosis of proximal myopathy, especially in at-risk individuals. Vitamin D deficiency and its prevention remain important health issues in industrialized countries.

Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate.

OBJECTIVES: The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. METHODS: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. RESULTS: A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). CONCLUSIONS: The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.