A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460-kb CENP-A-binding neocentromere DNA

Centromere protein A (CENP-A) is an essential histone H3-related protein that constitutes the specialized chromatin of an active centromere. It has been suggested that this protein plays a key role in the epigenetic marking and transformation of noncentromeric genomic DNA into functional neocentromeres. Neocentromeres have been identified on more than two-thirds of the human chromosomes, presumably involving different noncentromeric DNA sequences, but it is unclear whether some generalized sequence properties account for these neocentromeric sites. Using a novel method combining chromatin immunoprecipitation and genomic array hybridization, we have identified a 460-kb CENP-A-binding DNA domain of a neocentromere derived from the 20p12 region of an invdup (20p) human marker chromosome. Detailed sequence analysis indicates that this domain contains no centromeric alpha-satellite, classical satellites, or other known pericentric repetitive sequence motifs. Putative gene loci are detected, suggesting that their presence does not preclude neocentromere formation. The sequence is not significantly different from surrounding non-CENP-A-binding DNA in terms of the prevalence of various interspersed repeats and binding sites for DNA-interacting proteins (Topoisomerase II and High-Mobility-Group protein I). Notable variations include a higher AT content similar to that seen in human alpha-satellite DNA and a reduced prevalence of long terminal repeats (LTRs), short interspersed repeats (SINEs), and Alus. The significance of these features in neocentromerization is discussed.     

Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers.

OBJECTIVE--To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN--Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS--12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. MAIN OUTCOME MEASURES--Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). RESULTS--Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). CONCLUSIONS--The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications.     

Burden of caregiving in mild to moderate dementia: an Asian experience

This survey sought to determine (a) the prevalence of carer stress in patients with mild to moderate dementia, (b) whether caregiver burden was already associated with plans to institutionalize patients, and (c) which patient-related and caregiver-related variables best predicted caregiver burden. The principal caregivers of 93 Asian patients with mild to moderate dementia attending an outpatient cognitive assessment clinic were interviewed via a structured questionnaire that focused upon (a) patient-related variables such as their behavioral and functional abnormalities; and (b) caregiver-related variables such as whether they were having problems looking after the patients, the duration of their caregiving, their associated feelings of anger and/or depression, and their financial status as well as intentions to institutionalize patients. Forty-nine percent of caregivers reported problems in looking after the patients, and their perception of difficulties was significantly associated with institutionalization plans for the patients. Logistic regression analysis using a forward variable selection procedure showed two of the patients' behavioral abnormalities (repetition, agitation) and one of their functional impairments (urinary incontinence) as well as the carers' depressed feelings to be predictive of the carers' problematic status, explaining 40% of the variance. It is important that even in the early stages of dementia, the medical assessment also evaluate behavioral, functional, and social dimensions of the illness, so that appropriate interventions can be implemented to reduce caregiving burden and delay institutionalization.     

Exposure of expanded polytetrafluoroethylene-wrapped hydroxyapatite orbital implant: a report of two patients

PURPOSE: Hydroxyapatite (HA) spheres used to replace volume after an enucleation are often wrapped with autologous tissue before orbital implantation. Man-made materials are less expensive and pose no risk for viral transmission. The use of expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated. METHODS: The medical records of 2 consecutive patients who underwent uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed. RESULTS: An unusual reaction to the ePTFE material that was nonresponsive to topical or systemic antibiotic therapy developed in these 2 patients. Eventual wound erosion and bacterial infection of the implant necessitated its removal. CONCLUSIONS: Although well tolerated in other surgeries, ePTFE, when used to wrap HA spheres and placed into the orbit, may cause persistent conjunctival discharge, pyogenic granuloma formation, and eventual wound erosion. Therefore, the use of this material to wrap HA spheres is not recommended.     

Semiinvasive pulmonary aspergillosis: CT and pathologic findings in six patients

OBJECTIVE: We describe the chest CT and pathologic findings of semiinvasive pulmonary aspergillosis in six patients. CONCLUSION: Semiinvasive pulmonary aspergillosis should be considered in the mildly immunocompromised patient with CT findings that reveal persistent parenchymal abnormalities. Patterns include consolidation and mass.     

Synthesis and characterization of the biodegradable and elastic terpolymer poly(glycolide-co-L-lactide-co-ϵ-caprolactone) for mechano-active tissue engineering

We synthesized a series of tri-component biodegradable copolymers with elastic characteristics by ring-opening copolymerization of cyclic lactones, that is, glycolide, L-lactide, and ?-caprolactone, in the presence of stannous octoate as a catalyst. We evaluated the physical and chemical characteristics of poly(glycolide-co-L-lactide-co-?-caprolactone) (PGLCL) copolymers. The synthesized PGLCL had a high molecular weight of about 100?kD and an amorphous structure. It was confirmed that the physical and chemical properties of these terpolymers could be modulated by adjusting copolymer composition. PGLCL films exhibited rubber-like elasticity and showed almost complete recovery when subjected to 50% of the tensile strain. To examine the biodegradability of the PGLCL copolymers, we performed in vitro degradation tests for 12?weeks and observed changes in molecular weight, gross weight, and composition. These results showed that the glycolide was degraded most quickly and that ?-caprolactone was the slowest to degrade. Additionally, cytotoxicity tests revealed that none of the polymers were toxic. In summary, the mechanical properties and biodegradability of PGLCL terpolymers could be controlled by changing the monomer content, which may be useful for a wide range of tissue engineering applications based on mechanical property requirements.     

A novel audio forensic data-set for digital multimedia forensics

Today, digital multimedia (audio, video, images) is a common evidential source in litigation and criminal justice proceedings, and, not surprisingly, multimedia forensics is an active research area. One particular challenge faced by multimedia forensic researchers is the lack of a comprehensive and publicly available data-set for evaluating existing and new algorithms. This paper presents a digital audio forensic data-set, designed to facilitate evaluation of audio forensic algorithms (e.g. microphone identification, acoustic environment identification and splice detection). This paper also briefly describes the data-collection settings, microphones, speakers, languages and notations used. Existing tamper-detection techniques rely on artefacts due to recording devices, codec and/or the acoustic environment in the audio in question. Experimental results show that the selected approaches achieved promising results.