Fast Detection of Unexpected Sound Intensity Decrements as Revealed by Human Evoked Potentials

The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN), an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR) and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN) a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits

Differences in perceptions on sexual and reproductive health between service providers and people living with HIV: a qualitative elicitation study

The sexual and reproductive health (SRH)-related needs of people living with HIV/AIDS (PLHA) have not been sufficiently recognised in research and clinical care. Fifteen study sites in 13 European countries participated in this qualitative study to assess differences in perceptions between service providers (SP) and PLHA on SRH-related problems and needs of PLHA. Factors influencing SRH were determined to collect evidence on how to improve service provision. Qualitative data were obtained using an interpretative ethnographical approach. Data were analysed inductively on country level; a cross country data matrix was developed to facilitate the contextual analysis. Thirty-seven FGD discussions were organised with a total of 254 participants. A short survey was distributed to assess demographic characteristics. Results revealed insufficient information and lack of behavioural skills regarding SRH issues among PLHA. Intra- and interpersonal, provider-related, and social factors were found to influence the SRH behaviours of PLHA. Although from patients' perception SRH is a prioritised issue, it rarely comes up during routine HIV clinical care. SP need adequate counseling training to tackle SRH-related issues. A better integration between HIV care programs and SRH care settings is needed to improve effective service provision

Molecular Mapping of Sinoatrial Node HCN Channel Expression in the Human Heart.

BACKGROUND: The hyperpolarization-activated current, I(f), plays an important role in sinoatrial node (SAN) pacemaking. Surprisingly, the distribution of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels in human SAN has only been investigated at the mRNA level. Our aim was to define the expression pattern of HCN proteins in human SAN and different atrial regions. METHODS AND RESULTS: Entire SAN complexes were isolated from failing (n=5) and non-failing (n=9) human hearts cardioplegically-arrested in the operating room. Three dimensional intramural SAN structure was identified as the fibrotic compact region around the SAN artery with Connexin43-negative pacemaker cardiomyocytes visualized in Masson’s trichrome and immunostained cryosections. SAN protein was precisely isolated from the adjacent frozen SAN tissue blocks using a 16G biopsy needle. The purity of the SAN protein was confirmed by Connexin43 immunoblot. All three HCN isoform proteins were detected in SAN. HCN1 was predominantly distributed in the human SAN with a 125.1±40.2 (n=12) expression ratio of SAN to right atrium (RA). HCN2 and HCN4 expression levels were higher in SAN than atria with SAN to RA ratios of 6.1±0.9 and 4.6±0.6 (n=12), respectively. CONCLUSIONS: This is the first study to conduct precise 3D molecular mapping of the human SAN by isolating pure pacemaker SAN tissue. All three cardiac HCN isoforms had higher expression in the SAN than the atria. HCN1 was almost exclusively expressed in SAN, emphasizing its utility as a new specific molecular marker of the human SAN and as a potential target of specific treatments intended to modify sinus rhythm