ICF linking rules: an update based on lessons learned.

OBJECTIVE: Outcome research seeks to understand the end results of health services. Researchers use a wide variety of outcome measures including technical, clinical and patient-oriented measures. The International Classification of Functioning, Disability and Health (ICF) as a common reference framework for functioning may contribute to improved outcome research. The objective of this paper is to provide an updated version of the linking rules published in 2002 and illustrate how these rules are applied to link technical and clinical measures, health-status measures and interventions to the ICF. RESULTS: Three specific linking rules have been established to link health-status measures to the ICF and one specific linking rule has been created to link technical and clinical measures and interventions. A total of 8 linking rules have been established for use with all different outcome measures and with interventions. CONCLUSION: The newly updated linking rules will allow researchers systematically to link and compare meaningful concepts contained in them. This should prove extremely useful in selecting the most appropriate outcome measures among a number of candidate measures for the applied interventions. Further possible applications are the operationalization of concrete ICF categories using specific measures or the creation of ICF category-based item bankings.     

Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection

The purpose of this study was to investigate any influence of maternal and/or paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed retrospectively. While a significant linear decline in semen volume was detected, no significant differences in the concentration, motility or morphology of the spermatozoa were found with paternal ageing. A significant decline in the number of oocytes retrieved and the number of mature oocytes obtained was found with advancing maternal age. An increase in the occurrence of digyny was noted with parental ageing, while no difference in single or bipronuclear fertilization was found. Older women had a decreased incidence of single pronucleus formation and an increase in digyny, but no significant difference in the percentage of oocytes that underwent two-pronuclear fertilization was detected with regard to maternal ageing. Pregnancy outcomes were not influenced by the age of the male partner, while a strong negative correlation was found with maternal ageing. To better analyse male partner ageing as a factor affecting pregnancy outcome, we analysed a subgroup of patients with a female partner aged <35 years who underwent ICSI. No paternal influence on ICSI pregnancy outcome was found in this subgroup of patients. We conclude that the influence on pregnancy outcome after ICSI is related mostly to maternal and not paternal age.      

Endocannabinoids and Reactive Nitrogen and Oxygen Species in Neuropathologies

Neuropathologies that affect our population include ischemic stroke and neurodegenerative diseases of immune origin, including multiple sclerosis. The endocannabinoid system in the brain, including agonists anandamide (arachidonyl ethanolamide) and 2-arachidonoylglycerol, and the CB₁ and CB₂ cannabinoid receptors, has been implicated in the pathophysiology of these disease states, and can be a target for therapeutic interventions. This review concentrates on cellular signal transduction pathways believed to be involved in the cellular damage.Support: National Institute on Drug Abuse U24-DA12385 (S.M. and D.C.N.), R01-DA03690 and K05-00182 (A.C.H.), the American Heart Association Beginning Grant in Aid (S.M.), National Institute of General Medical Sciences S06 GM08049 (D.C.N.), and the National Center on Minority Health and Health Disparities P20-MD00175 (D.C.N. and A.C.H.).Meeting: Mechanisms of Toxicity, Toxicokinetics, and Medical Consequences of Drugs, Substances of Abuse and AIDS. Date: November 4–5, 2005. Place: Nashville, TN. A Satellite Meeting to the American Association of Pharmaceutical Scientists (AAPS). Co-Sponsors: DDD Section, Drug Metabolism Focus Group (DFG). Sponsored by the AIDS Office, NIDA Chairs: Rao S. Rapaka, Ph.D., NIDA/NIH, and Ho-Leung Fung, Ph.D., SUNY, Buffalo, NY.     

Mutations in the calcium-related gene IL1RAPL1 are associated with autism

In a systematic sequencing screen of synaptic genes on the X chromosome, we have identified an autistic female without mental retardation (MR) who carries a de novo frameshift Ile367SerfsX6 mutation in Interleukin-1 Receptor Accessory Protein-Like 1 (IL1RAPL1), a gene implicated in calcium-regulated vesicle release and dendrite differentiation. We showed that the function of the resulting truncated IL1RAPL1 protein is severely altered in hippocampal neurons, by measuring its effect on neurite outgrowth activity. We also sequenced the coding region of the close related member IL1RAPL2 and of NCS-1/FREQ, which physically interacts with IL1RAPL1, in a cohort of subjects with autism. The screening failed to identify non-synonymous variant in IL1RAPL2, whereas a rare missense (R102Q) in NCS-1/FREQ was identified in one autistic patient. Furthermore, we identified by comparative genomic hybridization a large intragenic deletion of exons 3-7 of IL1RAPL1 in three brothers with autism and/or MR. This deletion causes a frameshift and the introduction of a premature stop codon, Ala28GlufsX15, at the very beginning of the protein. All together, our results indicate that mutations in IL1RAPL1 cause a spectrum of neurological impairments ranging from MR to high functioning autism.