Gradients of response latencies and temporal precision of auditory neurons extend across the whole inferior colliculus.

Neural responses to acoustic stimulation have long been studied throughout the auditory system to understand how sound information is coded for perception. Within the inferior colliculus (IC), a majority of the studies have focused predominantly on characterizing neural responses within the central region (ICC), as it is viewed as part of the lemniscal system mainly responsible for auditory perception. In contrast, the responses of outer cortices (ICO) have largely been unexplored, though they also function in auditory perception tasks. Therefore, we sought to expand on previous work by completing a three-dimensional (3-D) functional mapping study of the whole IC. We analyzed responses to different pure tone and broadband noise stimuli across all IC subregions and correlated those responses with over 2,000 recording locations across the IC. Our study revealed there are well-organized trends for temporal response parameters across the full IC that do not show a clear distinction at the ICC and ICO border. These gradients span from slow, imprecise responses in the caudal-medial IC to fast, precise responses in the rostral-lateral IC, regardless of subregion, including the fastest responses located in the ICO. These trends were consistent at various acoustic stimulation levels. Weaker spatial trends could be found for response duration and spontaneous activity. Apart from tonotopic organization, spatial trends were not apparent for spectral response properties. Overall, these detailed acoustic response maps across the whole IC provide new insights into the organization and function of the IC.NEW & NOTEWORTHY Study of the inferior colliculus (IC) has largely focused on the central nucleus, with little exploration of the outer cortices. Here, we systematically assessed the acoustic response properties from over 2,000 locations in different subregions of the IC. The results revealed spatial trends in temporal response patterns that span all subregions. Furthermore, two populations of temporal response types emerged for neurons in the outer cortices that may contribute to their functional roles in auditory tasks.

Quantifying Cardiothoracic Variation with Posture and Respiration to Inform Cardiac Device Design.

PURPOSE: With extravascular implantable cardioverter defibrillator leads placed beneath the sternum, it is important to quantify heart motion relative to the rib cage with postural changes and respiration. METHODS: MRI scans from five males and five females were collected in upright and supine postures at end inspiration [n = 10 each]. Left and right decubitus [n = 8 each] and prone [n = 5] MRIs at end inspiration and supine MRIs at end expiration [n = 5] were collected on a subset. Four cardiothoracic measurements, six cardiac measurements, and six cardiac landmarks were collected to measure changes across different postures and stages of respiration. RESULTS: The relative location of the LV apex to the nearest intercostal space was significantly different between the supine and decubitus postures (average ± SD difference: - 15.7 ± 11.4 mm; p < 0.05). The heart centroid to xipho-sternal junction distance was 9.7 ± 7.9 mm greater in the supine posture when compared to the upright posture (p < 0.05). Cardiac landmark motion in the lateral direction was largest due to postural movement (range 23-50 mm) from the left decubitus to the right decubitus posture, and less influenced by respiration (5-17 mm). Caudal-cranial displacement was generally larger due to upright posture (13-23 mm caudal) and inspiration (7-20 mm cranial). CONCLUSIONS: This study demonstrates that the location of the heart with respect to the rib cage varies with posture and respiration. The gravitational effects of postural shifts on the heart position are roughly 2-3 times larger than the effects of normal respiration.

Imaging-Based Localization of His Bundle Pacing Electrodes: Results From the Prospective IMAGE-HBP Study.

OBJECTIVES: This study sought to evaluate the correlation between His bundle (HB) pacing (HBP) implantation characteristics, lead-tip location, and association of intraprocedural His recordings with approximated HB anatomic landmarks using computed tomography (CT) imaging. BACKGROUND: HBP continues to grow in clinical practice due to offering true physiological pacing. However, a clear understanding of HB anatomy and the lead-tip location's influence on pacing characteristics is lacking. METHODS: The IMAGE-HBP study (Imaging Study of Lead Implant for His Bundle Pacing) was a prospective, multicenter study designed to assess implantation characteristics of the SelectSecure Model 3830 lead placed at the HB, evaluate protocol-specified HBP success (His recording present on electrogram and HBP threshold ≤2.5 V at 1 ms), and correlation between lead-tip location by CT imaging and HBP characteristics as well as lead-related complications through 12 months. RESULTS: Sixty-nine patients underwent a lead implantation attempt at the HB. Of these, 61 patients (88%) had a lead successfully implanted at the HB, and 52 patients (75%) met the pre-specified definition of successful HBP. In 51 patients with CT imaging, 11 leads (22%) were placed in the atrial aspect of the HB region (36% selective HBP), and 40 leads (78%) were placed in the ventricular aspect (28% selective HBP). Four of the 51 patients had P-wave oversensing, all with leads in the atrium. Freedom from lead-related complication at 12 months was 93%. CONCLUSIONS: Successful HBP could be achieved at lead-tip locations in the atrium or ventricle but is preferable in the ventricle to eliminate risk of oversensing. The IMAGE-HBP study offers better insight into approximated HB anatomic landmarks, lead-tip location, and correlation with pacing characteristics. (Imaging Study of Lead Implant for His Bundle Pacing [IMAGE-HBP]; NCT03294317).

Development and application of loop-mediated isothermal amplification assays on rapid detection of various types of staphylococci strains.

A loop-mediated isothermal amplification (LAMP) method for rapid detection of various Staphylococcus strains and associated antibiotic resistance determinant had been developed and evaluated in this study. Six primers, including outer primers, inner primers and loop primers, were specially designed for recognizing eight distinct sequences on three targets: 16SrRNA, femA and mecA.. Forty-one reference strains, including various species of gram-negative and -positive isolates, were included in this study to evaluate and optimize LAMP assays. The optimal reaction condition was found to be 65 °C for 45 min, with detection limits at 100 fg DNA/tube and 10 CFU/reaction for 16S rRNA, 100 fg DNA/tube and 10 CFU/reaction for femA, 1 pg DNA/tube and 100 CFU/reaction for mecA, respectively. Application of LAMP assays were performed on 118 various types of Staphylococcus isolates, the detection rate of LAMP assays for the 16SrRNA, femA and mecA was 100% (118/118), 98.5% (64/65) and 94.3% (66/70), and the negative predictive value (NPV) was 100%, 98.1% and 92.3% respectively; with a 100% positive predictive value (PPV) for all three targets. In conclusion, LAMP assays were demonstrated to be useful and powerful tools for rapid detection of various Staphylococcus strains, and undoubtedly, the rapidness, technical simplicity, and cost-effectiveness of LAMP assays will demonstrate broad application for bacteriological detection of food-borne Methicillin-resistant Staphylococcus (MRS) isolates.

Farnesol-induced apoptosis in Candida albicans.

Farnesol, a precursor in the isoprenoid/sterol pathway, was recently identified as a quorum-sensing molecule produced by the fungal pathogen Candida albicans. Farnesol is involved in the inhibition of germination and biofilm formation by C. albicans and can be cytotoxic at certain concentrations. In addition, we have shown that farnesol can trigger apoptosis in mammalian cells via the classical apoptotic pathways. In order to elucidate the mechanism behind farnesol cytotoxicity in C. albicans, the response to farnesol was investigated, using proteomic analysis. Global protein expression profiles demonstrated significant changes in protein expression resulting from farnesol exposure. Among the downregulated proteins were those involved in metabolism, glycolysis, protein synthesis, and mitochondrial electron transport and the respiratory chain, whereas proteins involved in folding, protection against environmental and oxidative stress, actin cytoskeleton reorganization, and apoptosis were upregulated. Cellular changes that accompany apoptosis (regulated cell death) were further analyzed using fluorescent microscopy and gene expression analysis. The results indicated reactive oxygen species accumulation, mitochondrial degradation, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) in the farnesol-exposed cells concurrent with increased expression of antioxidant-encoding and drug response genes. More importantly, the results demonstrated farnesol-induced upregulation of the caspase gene MCA1 and the intracellular presence of activated caspases. In conclusion, this study demonstrated that farnesol promotes apoptosis in C. albicans through caspase activation, implying an important physiological role for farnesol in the fungal cell life cycle with important implications for adaptation and survival.

An assessment of PCBs and OC pesticides in eggs of double-crested (Phalacrocorax auritus) and Pelagic (P. pelagicus) cormorants from the west coast of Canada, 1970 to 2002.

Eggs of double-crested and pelagic cormorants were collected between 1970 and 2002 from colonies in the Strait of Georgia, BC, Canada, and assayed for concentrations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs). Double-crested cormorant eggs from the early 1970's contained up to 4.1 mg kg-1 p,p'-DDE and 12.5 mg kg-1 sigmaPCBs. Corresponding values for pelagic cormorant eggs were 1.5 mg kg-1 p,p'-DDE and 3.9 mg kg-1 sigmaPCBs. Egg tissue concentrations of the dominant OC pesticides and sigmaPCBs dropped mainly during the 1970's, with minor declines thereafter. The data suggest that contaminant levels in cormorants have now stabilized at low levels throughout the resident population. Small but significant latitudinal gradients in several OC pesticides and PCBs indicated that areas of the southern strait were more contaminated than areas of the less populated northern strait. Interspecific differences in contamination may indicate that pelagic cormorants have a reduced capacity to metabolize chlordanes, DDT and PCBs compared to double-crested cormorants. Alternatively, the two species may have more divergent prey bases than previously thought. During the 1980's, TCDD toxic equivalents, largely contributed by polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), were correlated with physiological and biochemical alterations. Also, from 1989 to 1990, four deformed cormorant chicks (two of each species) were found during nest visits; none were found between 1991 and 1995. The relative rates of deformed chicks were 6 per 10,000 for double-crested and 16 per 10,000 for pelagic cormorants. The findings of deformed chicks were coincident with the period of highest PCDD and PCDF contamination; however, the sample sizes were too low to derive a substantive connection. Colony-wide productivity of double-crested cormorants was poorer in the southern colonies where PCBs in particular were elevated. While of concern, these lines of evidence are insufficient to conclude that chlorinated hydrocarbon contamination was a dominant contributor to population declines. It seems more probable that ecological variables, particularly changing prey and predator dynamics, drove the reductions in population size.

Egg concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans in double-crested (Phalacrocorax auritus) and pelagic (P. pelagicus) cormorants from the Strait of Georgia, Canada, 1973-1998.

Eggs of double-crested and pelagic cormorants were collected between 1973 and 1998 from colonies in the Strait of Georgia, BC, Canada, and assayed for concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non-ortho- and mono-ortho-biphenyls (PCBs). Double-crested cormorant eggs contained (on average) up to 433 ng kg(-1) wet weight 1,2,3,6,7,8-HxCDD, 151 ng kg(-1) 1,2,3,7,8-PnCDD, and 74 ng kg(-1) 2,3,7,8-TCDD, whereas pelagic cormorant eggs contained up to 300, 99, and 28 ng kg(-1) wet weight of these respective congeners. The dominant non-ortho-PCB was CB-126, which ranged as high as 2263 ng kg(-1) in double-crested cormorant eggs. Concentrations of PCDDs and PCDFs fell dramatically in the early 1990s, following both severe restrictions on the use of chlorophenolic wood preservatives and antisapstains and a switch from molecular chlorine bleaching to alternative bleaching technologies at pulp mills in the region. Concentrations of PCBs did not show similar marked declines over time. On the basis of total TEQs > or = 148 ng kg(-1) and previously published documentation of effects in siblings of the cormorant eggs analyzed here, double-crested cormorant young may have exhibited significantly elevated EROD activity and/or brain asymmetries at all colonies from 1973 to 1989 and even at some colonies during the 1990s. Pelagic cormorant eggs collected from a few colonies in 1988-1989 also contained total TEQs greater than the threshold value estimated for double-crested cormorants.