Prospective Ultrasound Screening of Men With Cerebrovascular Disease for Abdominal Aortic Aneurysms.

BACKGROUND: The prevalence of abdominal aortic aneurysms is higher in population with other vascular comorbidities, especially among men. Utility of screening among patients with cerebrovascular disease is unclear. OBJECTIVE: To determine the prevalence of abdominal aortic aneurysm in male patients with diagnosed cerebrovascular disease manifested by transient ischemic attack or stroke. METHODS: Between May 2013 and May 2014, all consecutive male patients undergoing carotid ultrasound in single tertiary center with a catchment area of 179,000 inhabitants were evaluated for ultrasound screening of abdominal aortic aneurysm. Abdominal aortic aneurysm was defined as maximum diameter of infrarenal aorta 30 mm or more. RESULTS: Of 105 (n = 105) consecutively evaluated male patients, only 69% (n = 72) were eligible for the study and underwent aortic screening. Reason for ineligibility was most often poor general medical condition (n = 29). Mean age of screened patients was 66 years (SD 9.8 years). Half of the screened patients suffered stroke (n = 36). The incidence of abdominal aortic aneurysm was 5.6% (n = 4). All found abdominal aortic aneurysms were small and did not require immediate surgical intervention. During a follow-up period of over 4 years, none of the aneurysms exhibited tendency for growth. CONCLUSIONS: The male population with cerebrovascular disease is comorbid and frail. Only, moderate prevalence of abdominal aortic aneurysms can be found in this subpopulation.

Late onset spinal motor neuronopathy is caused by mutation in CHCHD10.

OBJECTIVE: A study was undertaken to identify the responsible gene defect underlying late onset spinal motor neuronopathy (LOSMoN/SMAJ; Online Mendelian Inheritance in Man #615048), an autosomal dominant disease mapped to chromosome 22q11.2. METHODS: The previous genetic linkage approach by microsatellite haplotyping was continued in new families. A whole genome sequencing was performed to find all possibly pathogenic mutations in the linked area. The detected variations were verified by Sanger sequencing. RESULTS: Six new SMAJ families were identified based on the unique founder haplotype. A critical recombination in 1 family restricted the linked area to 727kb between markers SHGC-106816 and D22S345. In whole genome sequencing a previously unknown mutation c.197G>T p.G66V in CHCHD10 was identified. The mutation was shown to segregate with the disease in 55 patients from 17 families. INTERPRETATION: Mutation c.197G>T p.G66V in CHCHD10 is the cause of the lower motor neuron syndrome LOSMoN/SMAJ. During the preparation of this article other mutations were reported to cause frontotemporal dementia-amyotrophic lateral sclerosis syndrome, indicating that the CHCHD10 gene is largely important for the motor and cognitive neuronal systems.

Late-onset spinal motor neuronopathy - a common form of dominant SMA.

We previously described two Finnish families with a new autosomal dominant late-onset spinal motor neuronopathy that was mapped to chromosome 22q11.2-q13.2. In the current screening study of 43 lower motor neuron disease patients from Finland and Sweden, we identified 26 new late-onset spinal motor neuronopathy patients sharing the founder haplotype. In addition to the main symptoms and signs: painful cramps, fasciculations, areflexia and slowly evolving muscle weakness, new features such as mild bulbar findings, were identified. The disease is relatively benign in terms of life expectancy and rate of disability progression, and it is therefore noteworthy that three patients were initially misdiagnosed with ALS. Significant recombinants in this new patient cohort restricted the disease locus by 90% to 1.8Mb. Late-onset spinal motor neuronopathy seems not to be very rare, at least not in Finland, with 38 patients identified in a preliminary ascertainment.

Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on chromosome 22q11.2-q13.2.

Spinal muscular atrophies (SMAs) are hereditary disorders characterized by degeneration of lower motor neurons. Different SMA types are clinically and genetically heterogeneous and many of them show significant phenotypic overlap. We recently described the clinical phenotype of a new disease in two Finnish families with a unique autosomal dominant late-onset lower motor neuronopathy. The studied families did not show linkage to any known locus of hereditary motor neuron disease and thus seemed to represent a new disease entity. For this study, we recruited two more family members and performed a more thorough genome-wide scan. We obtained significant linkage on chromosome 22q, maximum LOD score being 3.43 at marker D22S315. The linked area is defined by flanking markers D22S686 and D22S276, comprising 18.9 Mb. The region harbours 402 genes, none of which is previously known to be associated with SMAs. This study confirms that the disease in these two families is a genetically distinct entity and also provides evidence for a founder mutation segregating in both pedigrees.

An adaptive multimeme algorithm for designing HIV multidrug therapies.

This paper proposes a period representation for modeling the multidrug HIV therapies and an Adaptive Multimeme Algorithm (AMmA) for designing the optimal therapy. The period representation offers benefits in terms of flexibility and reduction in dimensionality compared to the binary representation. The AMmA is a memetic algorithm which employs a list of three local searchers adaptively activated by an evolutionary framework. These local searchers, having different features according to the exploration logic and the pivot rule, have the role of exploring the decision space from different and complementary perspectives and, thus, assisting the standard evolutionary operators in the optimization process. Furthermore, the AMmA makes use of an adaptation which dynamically sets the algorithmic parameters in order to prevent stagnation and premature convergence. The numerical results demonstrate that the application of the proposed algorithm leads to very efficient medication schedules which quickly stimulate a strong immune response to HIV. The earlier termination of the medication schedule leads to lesser unpleasant side effects for the patient due to strong antiretroviral therapy. A numerical comparison shows that the AMmA is more efficient than three popular metaheuristics. Finally, a statistical test based on the calculation of the tolerance interval confirms the superiority of the AMmA compared to the other methods for the problem under study.