Context A common allele on chromosome 9p21 has been repeatedly associated with increased risk of coronary artery disease (CAD) in the general population. However, the magnitude of this effect in the population with diabetes has not been well characterized. Objective To examine the association of the 9p21 variant with CAD in individuals with type 2 diabetes and evaluate its interaction with poor glycemic control. Design, Setting, and Participants 1. Case-control study of 734 type 2 diabetic patients (322 with angiographically-diagnosed CAD and 412 with no evidence of CAD) who were recruited in 2001–2006 at the Joslin Clinic/Beth Israel Deaconess Medical Center, 2. Independent cohort study of 475 type 2 diabetic patients from the Joslin Clinic whose survival status was monitored from their recruitment in 1993–1996 until December 31, 2004. Study subjects were genotyped for a representative SNP at 9p21 (rs2383206) and characterized for their long-term glycemic control by averaging multiple hemoglobin A1c (HbA1c) measurements taken in the years before study entry. Main Outcome Measures Case-control study: association between SNP rs2383206 and CAD defined as angiographically documented stenosis greater than 50% in a major coronary artery or a main branch thereof. Cohort study: cumulative 10-year mortality. Results Individuals homozygous for the risk allele were significantly more frequent in case than control subjects (42.3 vs. 28.9%, p=0.0002). This association was unaffected by adjustment for cardiovascular risk factors, but the effect of the risk genotype was significantly magnified (adjusted p for interaction = 0.048) in the presence of poor glycemic control (worst tertile of the distribution of HbA1c at examination). Relative to the CAD risk for patients with neither a 9p21 risk allele nor poor glycemic control, the CAD risk for subjects having two risk alleles but not poor glycemic control was increased two-fold (OR=1.99, 1.17–3.41), whereas the risk for study subjects with the same genotype and with poor glycemic control was increased four-fold (OR=4.27, 2.26–8.01). The interaction was stronger (adjusted p=0.005) when a measure of long-term glycemic control (7-year average rather than most recent HbA1c) was used, with ORs of 7.83 (3.49–17.6) for subjects having two risk alleles and a history of poor glycemia and 1.54 (0.72–3.30) for subjects with the same genotype but without this exposure. A similar interaction between 9p21 variant and poor glycemic control was observed with respect to cumulative 10-year mortality in the cohort study (43.6% in patients with two risk alleles and poor glycemic control, 23.1% in those with only the two risk alleles, 30.0% in those with only poor glycemic control, and 31.6% in those with neither factor, p for interaction=0.036). Conclusions In this study population, the CAD risk associated with the 9p21 variant was increased in the presence of poor glycemic control in type 2 diabetes.

Although the tonotopic organisation of the human primary auditory cortex (PAC) has already been studied, the question how its responses are affected in sensorineural hearing loss remains open. Twenty six patients (aged 38.1 ± 9.1 years; 12 men) with symmetrical sloping sensorineural hearing loss (SNHL) and 32 age- and gender-matched controls (NH) participated in an fMRI study using a sparse protocol. The stimuli were binaural 8s complex tones with central frequencies of 400 Hz, 800 Hz, 1600 Hz, 3200 Hz, or 6400 Hz, presented at 80 dB(C). In NH responses to all frequency ranges were found in bilateral auditory cortices. The outcomes of a winnermap approach, showing a relative arrangement of active frequency-specific areas, was in line with the existing literature and revealed a V-shape high-frequency gradient surrounding areas that responded to low frequencies in the auditory cortex. In SNHL frequency-specific auditory cortex responses were observed only for sounds from 400 Hz to 1600 Hz, due to the severe or profound hearing loss in higher frequency ranges. Using a stringent statistical threshold (p < 0.05; FWE) significant differences between NH and SNHL were only revealed for mid and high-frequency sounds. At a more lenient statistical threshold (p < 0.001, FDRc), however, the size of activation induced by 400 Hz in PAC was found statistically larger in patients with a prelingual, as compared to a postlingual onset of hearing loss. In addition, this low-frequency range was more extensively represented in the auditory cortex when outcomes obtained in all patients were contrasted with those revealed in normal hearing individuals (although statistically significant only for the secondary auditory cortex). The outcomes of the study suggest preserved patterns of large-scale tonotopic organisation in SNHL which can be further refined following auditory experience, especially when the hearing loss occurs prelingually. SNHL can induce both enlargement and reduction of the extent of responses in the topically organized auditory cortex.

Blood is not always available in forensic autopsies, therefore, the search for alternative sampling materials is needed. This study aimed at examining if ethanol can be detected in costal cartilage and to investigate if different forms of costal cartilage can give accurate information about ethanol concentration in the blood or urine of human cadavers (n = 50). Ethanol concentration in samples of unground costal cartilage (UCC), ground costal cartilage (GCC), femoral venous blood, and urine was analyzed using a gas chromatography-flame ionization detector (GC-FID). Due to Polish law, we used two different cut-off points: the blood alcohol concentration >0.2 mg/mL defined as the ‘after use’ condition, and the blood alcohol concentration >0.5 mg/mL defined as the ‘state of insobriety’. Based on the constructed receiver operating characteristics (ROC) curves, the optimal cut-off point for ethanol content as the ‘after use’ condition was 0.273 mg/g for the UCC method and 0.069 mg/g for the GCC method. Analysis of the Areas under a ROC Curve (AUC) showed that both methods present excellent diagnostic accuracy (AUCUCC = 0.903; AUCGCC = 0.984). We demonstrated that it is possible to detect ethanol in the costal cartilage and showed that ethanol concentrations are determined in GCC samples with greater accuracy.

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Alpha rhythm, described by Hans Berger, is mainly recorded from the occipital cortex (OCC) of relaxed subjects with their eyes closed.Early studies indicated the thalamo-cortical circuit as the origin of alpha rhythm. Recent works suggest an additional relationship between alpha rhythm and the Default Mode Network (DMN). We simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) signals in 36 young males asked to alternately close and open their eyes in 30-s blocks.Using an EEG source channel montage (the recorded signal was interpolated to designated source positions corresponding to certain brain regions) we found an alpha rhythm sub-activity composed of its intrinsic events, called alpha bursting segments (ABS). More ABS were observed on source channels related to the DMN than those located over the OCC. Similarly, both the beamformer source analysis and fMRI indicated that the specific ABS activity detected on the posterior cingulate cortex/precuneus (PCC) source channel was less related to the OCC than to the DMN source channels. The fMRI analysis performed using the PCC-ABS as a general linear model regressor indicated an increased blood oxygenation level-dependent signal change in DMN nodes -precuneus and prefrontal cortex. These results confirm the OCC source of alpha activity and additional specific sources of ABS in the DMN.

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Objective:The aim of the study was to develop a Markov model and apply it for the evaluation of three different treatment scenarios for adult patients with severe to profound bilateral sensorineural hearing loss.Study Design:Prospective Observational Study.Settings:Hospital.Patients:A clinical group of 22 adult patients (59.1% men, 40.9% women) aged from 59.13 ± 8.9 years were included in the study. The study comprised two arms: patients in group 1 received the second cochlear implant one to three months after the first implant; while patients in group 2 got the second cochlear implant approximately one year after the first implant.Main Outcome Measures:All participants were first asked to complete an AQoL-8D questionnaire. For the cost-effectiveness analyses, a Markov model analyzed as microsimulation was developed to compare the different treatment options.Results:The analyses show that bilateral cochlear implantation strategies are cost-effective compared to the ‘no treatment’ alternative when having a 10-year model time horizon. When all three model scenarios are compared, the bilateral simultaneous cochlear implantation strategy (Scenario 3) compared to the ‘no treatment’ option is even more cost-effective than the Scenarios 1 and 2, compared with the ’no treatment’ alternative.Conclusions:The model results summarize that bilateral (sequential and simultaneous) cochlear implantation that are represented in the model scenarios, are cost-effective strategies for Polish adult patients with bilateral severe to profound sensorineural hearing loss.

Theory of mind (ToM) is crucial for social interactions. Previous research has indicated that deaf and hard-of-hearing children born into hearing families (DoH) are at risk of delayed ToM development. However, it is unclear whether this is the case for DoH children who receive cochlear implants (CIs) before and around the second year of life. The present study aimed to investigate false belief understanding (FBU) in DoH children with CIs. The relationships between false belief task (FBT) performance, sentence comprehension, age at implantation, duration of CI use, and Speech Recognition Threshold were explored. A total of 94 children with typical levels of hearing (TH) and 45 DoH children (age range: 3–8), who received their first CI between 6 and 27 months of age, were tested on the FBT and a sentence comprehension test. Results showed that 4- and 5-year-old children with CIs performed significantly worse than their peers with TH on the FBT; 6- to 8-year-old children with CIs performed similarly to age-matched children with TH. Age at implantation and duration of CI use were correlated with sentence comprehension but not with the FBT. The results indicated that FBU was delayed until the age of 6 years in most of children with CIs.