Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome

Background: Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. Methods: To assess further the clinical implications of this novel 15q13.3 microdeletion syndrome, 18 new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. Results: The 15q13.3 microdeletion in our series was associated with a highly variable intra-and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognisable phenotype, but psychiatric disease was noted in 2 of 4 patients. Conclusions: Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with diagnostic difficulties and challenge the commonly used paradigm in the diagnostic setting that aberrations inherited from a phenotypically normal parent are usually without clinical consequences.

Ictal technetium-99 m ethyl cysteinate dimer single-photon emission tomographic findings in epileptic patients with polymicrogyria syndromes: A Subtraction of ictal-interictal SPECT coregistered to MRI study

Purpose To describe the ictal technetium-99 m-ECD SPECT findings in polymicrogyria syndromes (PMG) during epileptic seizures. Methods We investigated 17 patients with PMG syndromes during presurgical workup, which included long-term video-electroencephalographic (EEG) monitoring, neurological and psychiatry assessments, invasive EEG, and the subtraction of ictal-interictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM). Results The analysis of the PMG cortex, using SISCOM, revealed intense hyperperfusion in the polymicrogyric lesion during epileptic seizures in all patients. Interestingly, other localizing investigations showed heterogeneous findings. Twelve patients underwent epilepsy surgery, three achieved seizure-freedom, five have worthwhile improvement, and four patients remained unchanged. Conclusions Our study strongly suggests the involvement of PMG in seizure generation or early propagation. Both conventional ictal single-photon emission computed tomography (SPECT) and SISCOM appeared as the single contributive exam to suggest the localization of the epileptogenic zone. Despite the limited number of resective epilepsy surgery in our study (n=9), we found a strong prognostic role of SISCOM in predicting surgical outcome. This result may be of great value on surgical decision-making of whether or not the whole or part of the PMG lesion should be surgically resected.

The `club` cell and behavioural and physiological responses to chemical alarm cues in the Nile tilapia

The alarm response to skin extract has been well documented in fish. In response to skin extract, there is a decline in both locomotion activity and aggressive interactions. Our observation herein of these responses in the cichlid Nile tilapia, Oreochromis niloticus, confirmed the existence of the alarm response in this species. However, so far there has been a paucity of information on the autonomic correlates of this response. In this study, the ventilatory change in response to the chemical alarm cue was evaluated. This parameter was measured 4 min before and 4 min after exposure to 1 mL of either conspecific skin extract or distilled water (extract vehicle). Skin extract induced an increase in the ventilation rate, which suggested an anticipatory adjustment to potentially harmful stimuli. The chemical cue (alarm substance) also interfered with the prioritisation of responses to different environmental stimuli (stimuli filtering); this was suggested by the observation that the Nile tilapia declined to fight after exposure to a cue that indicates a risk of predation. Furthermore, histological analysis of the Nile tilapia skin revealed the presence of putative alarm substance-producing (club) cells.

Behavioural responses of heifers to ACTH injections

The objective of this study was to investigate behavioural changes in Holstein heifers caused by exogenous adrenocorticotropic hormone (ACTH) administration. Twelve 11-month-old heifers were submitted to either a single saline or ACTH injection and then the treatments were switched after 3 days (n = 12 heifers/treatment). Heifers were in full view throughout the experimental period and recordings started immediately after ACTH and saline administration (injection corresponded to time 0 min), with general activity patterns of each heifer recorded on videotape for 24 h. Behavioural results during the first two experimental hours showed that heifers were less active and spent more time lying following ACTH than after saline treatment (P = 0.04). Also, heifers spent significantly less time ruminating immediately following ACTH injection (P = 0.05). However, feed intake measured after 4 and 24 h was similar between treatments (P > 0.05). Overall, there was no significant influence of ACTH treatment on frequency or duration of behaviours during the 4- and 24-h periods following injection (P > 0.05). The rapid and minimal effect of ACTH injection on behaviour suggests that peripheral administration of ACTH can be used to measure reactivity of the adrenal cortex without inducing biologically significant consequences. (C) 2010 Elsevier B.V. All rights reserved.

Linking policies for biodiversity conservation with advances in behavioural economics

Global biodiversity loss and its consequences for human welfare and sustainable development have become major concerns. Economists have, therefore, given increasing attention to the policy issues involved in the management of genetic resources. To do so, they often apply empirical methods developed in behavioral and experimental economics to estimate economic values placed on genetic resources. This trend away from almost exclusive dependence on axiomatic methods is welcomed. However, major valuation methods used in behavioral economics raise new scientific challenges. Possibly the most important of these include deficiencies in the knowledge of the public (and researchers) about genetic resources, implications for the formation of values of supplying information to focal individuals, and limits to rationality. These issues are explored for stated-preference techniques of valuation (e.g., contingent valuation) as well as revealed preference techniques, especially the travel cost method. They are illustrated by Australian and Asian examples. Taking into account behavioral and psychological models and empirical evidence, particular attention is given to how elicitation of preferences, and supply of information to individuals, influences their preferences about biodiversity. Policy consequences are outlined.

Long-term risk stratification for survivors of acute coronary syndromes - Results from the long-term intervention with pravastatin in ischemic disease (LIPID) study

OBJECTIVES We developed a prognostic strategy for quantifying the long-term risk of coronary heart disease (CHD) events in survivors of acute coronary syndromes (ACS). BACKGROUND Strategies for quantifying long-term risk of CHD events have generally been confined to primary prevention settings. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, which demonstrated that pravastatin reduces CHD events in ACS survivors with a broad range of cholesterol levels, enabled assessment of long-term prognosis in a secondary prevention setting. METHODS Based on outcomes in 8,557 patients in the LIPID study, a multivariate risk factor model was developed for prediction of CHD death or nonfatal myocardial infarction. Prognostic indexes were developed based on the model, and low-, medium-, high- and very high-risk groups were defined by categorizing the prognostic indexes. RESULTS In addition to pravastatin treatment, the independently significant risk factors included: total and high density lipoprotein cholesterol, age, gender, smoking status, qualifying ACS, prior coronary revascularization, diabetes mellitus, hypertension and prior stroke. Pravastatin reduced coronary event rates in each risk level, and the relative risk reduction did not vary significantly between risk levels. The predicted five-year coronary event rates ranged from 5% to 19% for those assigned pravastatin and from 6.4% to 23.6% fur those assigned placebo. CONCLUSIONS Long-term prognosis of ACS survivors varied substantially according to conventional risk factor profile. Pravastatin reduced coronary risk within all risk levels; however, absolute risk remained high in treated patients with unfavorable profiles. Our risk stratification strategy enables identification of ACS survivors who remain at very high risk despite statin therapy. CT Am Coil Cardiol 2001;38:56-63) (C) 2001 by the American College of Cardiology.

Syndromes with salivary dysfunction predispose to tooth wear: case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjogren's syndromes.

Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjogren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear. Although there was evidence of consumption of highly acidic drinks, some occlusal parafunction, and unacceptable toothbrushing habits, salivary dysfunction was the salient factor predisposing a patient to tooth wear in these syndromal cases. The 500 subjects have been characterized either as having medical conditions and medications that predispose them to xerostomia or lifestyles in which workplace- and sports-related dehydration lead to reduced salivary flow. Normal salivation, by buffering capacity, clearance by swallowing, pellicle formation, and capacity for remineralization of demineralized enamel, protects the teeth from extrinsic and intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in many respects, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.