Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions

Microhomology (MH) flanking a DNA double-strand break (DSB) drives chromosomal rearrangements but its role in mutagenesis has not yet been analyzed. Here we determined the mutation frequency of a URA3 reporter gene placed at multiple locations distal to a DSB, which is flanked by different sizes (15-, 18-, or 203-bp) of direct repeat sequences for efficient repair in budding yeast. Induction of a DSB accumulates mutations in the reporter gene situated up to 14-kb distal to the 15-bp MH, but more modestly to those carrying 18- and 203-bp or no homology. Increased mutagenesis in MH-mediated end joining (MMEJ) appears coupled to its slower repair kinetics and the extensive resection occurring at flanking DNA. Chromosomal translocations via MMEJ also elevate mutagenesis of the flanking DNA sequences 7.1 kb distal to the breakpoint junction as compared to those without MH. The results suggest that MMEJ could destabilize genomes by triggering structural alterations and increasing mutation burden

The Prevalence and Evolution of Anemia Associated with Tuberculosis

Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (≤65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8±113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment

Is Cognitive Function in Adults with Hearing Impairment Improved by the Use of Hearing Aids?

ObjectivesIn the present study, we investigated whether speech-related cognitive function and speech recognition ability under background noise in adults with hearing impairment are improved with the use of hearing aids.MethodsParticipants were recruited from the ENT Department of Eulji Hospital from September 2008 to July 2009. The study group comprised 18 participants (mean age, 69.5±8.3 years) with sensorineural hearing loss who were fitted with hearing aids, and the control group comprised 11 participants of equivalent age (mean age, 63.1±11.8 years) who were not fitted with hearing aids. All participants were assessed using the computerized Korean visual verbal learning test (VVLT) and words-in-noise (WIN) test prior to fitting of hearing aids for the study group and initially for the control group. Both groups were reassessed in both tests after 6 months. For each group, differences in the results between the two assessments were compared using the Friedman test.ResultsThere was no difference in mean age between the study group and control group. In the study group, total VVLT score (reflecting short-term memory) was significantly improved from before hearing aid use to 6 months after hearing aid use (P0.05).ConclusionThe speech-related cognitive function of individuals with hearing impairment improved after using hearing aids. This finding indicates that hearing aids may induce acclimatization of the central auditory system

Hearing Abilities at Ultra-High Frequency in Patients with Tinnitus

ObjectivesTo compare tinnitus patients who have normal hearing between 250 Hz and 8 kHz with normal controls with regard to the ability of each group to hear extended high-frequency pure tone thresholds.MethodsWe enrolled 18 tinnitus patients, each of whom had a threshold of HL <25 dB and threshold differences of <10 dB between ears at frequencies of 250 and 500 Hz and 1, 2, 4, and 8 kHz. We also enrolled age- and gender-matched normal volunteers (10 ears), for each patient. Extended high frequency pure tone audiometry was performed, and the mean hearing thresholds at 10, 12, 14, and 16 kHz of each tinnitus ear were compared with those of the 10 age- and sex-matched normal ears.ResultsOf the 18 patients with tinnitus, 12 had significantly increased hearing thresholds at more than one of the four high frequencies, compared with the normal group. When we assessed results according to frequency, we found that 8 patients had decreased hearing ability at 10 kHz, 10 at 12 kHz, 8 at 14 kHz, and 4 at 16 kHz.ConclusionSome patients with tinnitus who have normal hearing below 8 kHz have decreased hearing ability at extended high-frequencies. Thus, the proportion of patients with tinnitus who have normal hearing over the entire audible range is smaller than in previous reports

Astroblastoma: A Case Report

Astroblastoma is one of the very unusual type of tumors, whose histogenesis has not been clarified. It occurs mainly among children or young adults. Astroblastoma is grossly well-demarcated, and shows histologically characteristic perivascular pseudorosettes with frequent vascular hyalinization. Perivascular pseudorosettes in astroblastoma have short and thick cytoplasmic processes and blunt-ended foot plates. A 15-yr-old girl presented with headache and diplopia for one and a half year. A well-demarcated mass, 9.7 cm in diameter, was found in the right frontal lobe in brain MRI, and it was a well-enhanced inhomogenous mass. Cystic changes of various sizes were observed inside the tumor mass as well as in the posterior part of the mass, but no peritumoral edema was found. Histologically, this mass belongs to a typical astroblastoma, and no sign of anaplastic astrocytoma, gemistocytic astrocytoma or glioblastoma was found in any part of the tumor. Immunohistochemically, the tumor cells showed diffuse strong positivity for glial fibrillary acidic protein, S-100 protein, vimentin and neuron specific enolase, and focal positivity for epithelial membrane antigen and CAM 5.2, while showing negativity for synaptophysin, neurofilament protein, pan-cytokeratin and high molecular weight keratin

Transcatheter Closure of Multiple Atrial Septal Defects With the Amplatzer Device

Percutaneous device occlusion of secundum atrial septal defect (ASD) has become an accepted alternative to surgical repair. A variety of devices have been used successfully. However, all of them have limitations. We report our experience with two devices used to close multiple ASDs

A comparison of the accuracy of ulnar versus median nerve stimulation for neuromuscular monitoring

BACKGROUND: Inexperienced anesthesiologists are frequently unclear as to whether to stimulate the ulnar or median nerve to monitor the adductor pollicis. The primary purpose of this study was to determine whether monitoring the adductor pollicis by positioning the stimulating electrodes over the median nerve is an acceptable alternative to applying electrodes over the ulnar nerve.0aMETHODS: In 20 patients anesthetized with propofol and remifentanil, one pair of stimulating electrodes was positioned over the ulnar nerve. A second pair was placed over the median nerve on the other hand. The acceleromyographic response was monitored on both hands. Rocuronium 0.6 mg/kg was administered. Single twitch (ST) and train-of-four (TOF) stimulations were applied alternatively to both sites.0aRESULTS: None of the patients showed a twitch response at either site after injection of rocuronium. There were no differences in the mean supramaximal threshold, mean initial TOF ratio, or mean initial ST ratio between the two sites. Bland-Altman analysis revealed a bias (limit of agreement) in the TOF and ST ratios over the median nerve of 7% (with that of the ulnar nerve value, and the median nerve ST ratio was overestimated by 72.9%, as compared to that of the ulnar nerve.0aCONCLUSIONS: The ulnar and median nerves cannot be used interchangeably for accurate neuromuscular monitoring