Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

Purpose

The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults.

Method

Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold.

Results

ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p p ² = .45). Adults had significantly larger wave V amplitudes to air- (p p ² = .50) and bone-conducted (p = .013, η_p² = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p p ² = .49) only with air-conducted CE-chirps.

Conclusion

The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea.

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Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

Purpose

The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults.

Method

Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold.

Results

ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p p ² = .45). Adults had significantly larger wave V amplitudes to air- (p p ² = .50) and bone-conducted (p = .013, η_p² = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p p ² = .49) only with air-conducted CE-chirps.

Conclusion

The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea.

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Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

Purpose

The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults.

Method

Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold.

Results

ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p p ² = .45). Adults had significantly larger wave V amplitudes to air- (p p ² = .50) and bone-conducted (p = .013, η_p² = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p p ² = .49) only with air-conducted CE-chirps.

Conclusion

The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea.

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Hearing Loss in HIV-Infected Children in Lilongwe, Malawi

by Susan Hrapcak, Hannah Kuper, Peter Bartlett, Akash Devendra, Atupele Makawa, Maria Kim, Peter Kazembe, Saeed Ahmed

Introduction

With improved access to antiretroviral therapy (ART), HIV infection is becoming a chronic illness. Preliminary data suggest that HIV-infected children have a higher risk of disabilities, including hearing impairment, although data are sparse. This study aimed to estimate the prevalence and types of hearing loss in HIV-infected children in Lilongwe, Malawi.

Methods

This was a cross-sectional survey of 380 HIV-infected children aged 4–14 years attending ART clinic in Lilongwe between December 2013-March 2014. Data was collected through pediatric quality of life and sociodemographic questionnaires, electronic medical record review, and detailed audiologic testing. Hearing loss was defined as >20 decibels hearing level (dBHL) in either ear. Predictors of hearing loss were explored by regression analysis generating age- and sex-adjusted odds ratios. Children with significant hearing loss were fitted with hearing aids.

Results

Of 380 patients, 24% had hearing loss: 82% conductive, 14% sensorineural, and 4% mixed. Twenty-one patients (23% of those with hearing loss) were referred for hearing aid fitting. There was a higher prevalence of hearing loss in children with history of frequent ear infections (OR 7.4, 4.2–13.0) and ear drainage (OR 6.4, 3.6–11.6). Hearing loss was linked to history of WHO Stage 3 (OR 2.4, 1.2–4.5) or Stage 4 (OR 6.4, 2.7–15.2) and history of malnutrition (OR 2.1, 1.3–3.5), but not to duration of ART or CD4. Only 40% of caregivers accurately perceived their child’s hearing loss. Children with hearing impairment were less likely to attend school and had poorer emotional (p = 0.02) and school functioning (p = 0.04).

Conclusions

There is an urgent need for improved screening tools, identification and treatment of hearing problems in HIV-infected children, as hearing loss was common in this group and affected school functioning and quality of life. Clear strategies were identified for prevention and treatment, since most hearing loss was conductive in nature, likely due to frequent ear infections, and many children with hearing loss qualified for hearing aids. Screening strategies need to be developed and tested since caregivers were not reliable at identifying hearing loss, and often mis-identified children with normal hearing as having hearing loss. Children with frequent ear infections, ear drainage, TB, severe HIV disease, or low BMI should receive more frequent ear assessments and hearing evaluations.

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Targeting HMGA2 in Retinoblastoma Cells in vitro Using the Aptamer Strategy

High-mobility group A2 (HMGA2) protein regulates retinoblastoma (RB) cancer cell proliferation. Here, a stable phosphorothioate-modified HMGA2 aptamer was used to block HMGA2 protein function in RB cells. HMGA2-aptamer internalisation in RB cells (Y79, Weri Rb1) and non-neoplastic human retinal cells (MIO-M1) were optimised. Aptamer induced dose-dependent cytotoxicity in RB cancer cells (0.25-1.5 µM). Increased expression of TGFβ, SMAD4, CDH1, BAX, CASP 3, PARP mRNA and decreased SNAI1, Bcl2 mRNA levels in aptamer-treated RB cells suggests the activation of TGFβ-SMAD4-mediated apoptotic pathway. Synergistic effect with etoposide was observed in aptamer treated RB cells (p value ≤0.05). No significant toxicity was observed in non-neoplastic retinal cells.
Ocul Oncol Pathol 2016;2:262-269

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Beweggründe von Krebspatienten für und gegen die Inanspruchnahme der Misteltherapie

Forsch Komplementmed

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Circulating Erythrocyte Microparticles and the Biochemical Extent of Myocardial Injury in ST Elevation Myocardial Infarction

Objectives: Red blood cell microparticles (RBCm) have potential adverse vascular effects and they have been shown to be elevated in ST elevation myocardial infarction (STEMI). The purpose of this study is to investigate their relationship with biochemical infarct size. Methods: RBCm were quantified with flow cytometry in blood drawn from 60 STEMI patients after a primary angioplasty. The creatine kinase-myocardial brain fraction (CK-MB) was measured at predefined time points and the area under the curve (AUC) was calculated. Results: RBCm count was correlated with CK-MB AUC (Spearman's #x03C1; = 0.83, p Conclusions: Erythrocyte microparticles appear to be related to the total myocardial damage biomarker output. The exact pathophysiologic routes, if any, for this interaction remain to be identified. However, these results suggest that erythrocytes may be a - thus far virtually ignored - player in the pathogenesis of ischemic injury.
Cardiology 2017;136:15-20

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Hepatitis B e Antigen Expression by Hepatitis B Virus Subgenotype A1 Relative to Subgenotypes A2 and D3 in Cultured Hepatocellular Carcinoma (Huh7) Cells

Background: Hepatitis B virus (HBV) is hyperendemic in southern Africa, with subgenotype A1 prevailing. The precore/core (preC/C) region of A1, encoding for hepatitis B e antigen (HBeAg), has unique sequence characteristics, differentiating it from subgenotypes A2 and D3. Our aim was to follow the expression of HBeAg in vitro by the three subgenotypes. Methods: Huh7 cells were transfected with plasmids belonging to subgenotypes A1, A2, and D3. Using indirect immunofluorescence, the expression of HBeAg was followed, as was the activation of the unfolded protein response (UPR) and subsequent activation of apoptosis. Results and Conclusions: Following transfection with D3, HBeAg passed through the secretory pathway earlier than cells transfected with genotype A. Cells transfected with A1 showed a lower expression of the preC/C precursor in the secretory pathway and a higher co-localization in the nucleus. Cells transfected with A1 showed greater endoplasmic reticulum (ER) stress and an earlier, prolonged activation of the UPR seen by the higher activity of three ER-localized transmembrane transducers (double-stranded RNA-dependent protein kinase-like ER kinase, activating transcription factor 6, and inositol-requiring enzyme 1), on day 3 compared to day 5. Moreover, our study also found that cells transfected with A1 had increased apoptosis.
Intervirology 2016;59:48-59

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Nivolumab-Induced Pericardial Tamponade: A Case Report and Discussion

Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life-threatening immune-related side effects may still occur and clinical vigilance is required.
Cardiology 2017;136:49-51

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Impact of Pulmonary Artery Catheter Use on Short- and Long-Term Mortality in Patients with Cardiogenic Shock

Objectives: The impact of pulmonary artery catheterization (PAC) on survival in patients with cardiogenic shock (CS) is not well established. This study aimed to assess whether Swan-Ganz catheter monitoring is related to short- and long-term mortality in patients with CS. Methods: One hundred and twenty-nine consecutive patients with a first admission for CS were prospectively enrolled in a single-center registry between December 2005 and May 2009, and were subsequently followed up over 5.3 years. Results: PAC was used in 64% of all patients with a mean age of 68 years (65% men). After adjustment for age, gender and the presence of CS upon admission, PAC was associated with lower short-term mortality [hazard ratio (HR) = 0.55, 95% confidence interval (CI) 0.35-0.86, p = 0.008] as well as lower mortality rates in the long-term follow-up (HR = 0.63, 95% CI 0.41-0.97, p = 0.035). In a subgroup analysis, the use of PAC was associated with reduced mortality in patients without acute coronary syndrome (ACS), i.e. 49% in the Swan-Ganz group vs. 82% (p = 0.010), but there was no difference within the ACS group. Conclusions: The use of PAC in patients with CS was associated with lower short- and long-term mortality rates after adjustment for age, gender and the presence of shock upon admission. This benefit was only significant in those patients without ACS.
Cardiology 2017;136:61-69

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Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes

Objectives: Accumulating evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes, making BMSCs a promising source of cardiomyocytes for transplantation. However, little is known about the molecular mechanisms underlying myogenic conversion of BMSCs. Methods: This study was designed to investigate the functional role of caveolin-1 in the cardiomyocyte differentiation of BMSCs and to explore the potential underlying molecular mechanisms. Results: BMSC differentiation was induced by treatment with 10 μM 5-azacytidine, and immunofluorescence assay showed that the expression of cardiomyocyte marker cardiac troponin T (cTnT) was significantly increased compared with a control group. Meanwhile, an increased caveolin-1 expression was found during the 5-azacytidine-induced BMSC differentiation. Additionally, the role of caveolin-1 in the differentiation process was then studied by using caveolin-1 siRNAs. We found that silencing caveolin-1 during induction remarkably enhanced the expression of cardiomyocyte marker genes, including cTnT, Nkx2.5 (cardiac-specific transcription factor), α-cardiac actin and α-myosin heavy chain (α-MHC). Moreover, we observed that downregulation of caveolin-1 was accompanied by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Conclusions: Taken together, these findings demonstrate that caveolin-1 plays an important role in the differentiation of BMSCs into cardiomyocytes in conjunction with the STAT3 pathway.
Cardiology 2017;136:40-48

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COPD und Klangtherapie: Pilotstudie zur Wirksamkeit einer Behandlung mit Körpertambura bei COPD-Patienten

Forsch Komplementmed

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Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Objectives: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. Methods: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion. Results: A systematic review revealed 10 eligible publications. Sotalol was superior to placebo and/or no antiarrhythmic therapy in AF conversion, with a relative success of 24 (95% CI 4.7-119, p Conclusions: Sotalol is as effective as class IA and class IC antiarrhythmic agents, and it is also as effective as amiodarone for pharmacologic conversion of AF. Only ibutilide at a high dose showed a greater conversion rate of AF.
Cardiology 2017;136:52-60

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The Comparative Molecular Epidemiology of GII.P7_GII.6 and GII.P7_GII.7 Norovirus Outbreaks in Victoria, Australia, 2012-2014

The comparative molecular epidemiology of the related GII.P7_GII.6 and GII.P7_GII.7 noroviruses has not been examined in detail. ORF 1, ORF 2 and ORF 1/ORF 2 RT-PCR as well as sequencing and phylogeny analysis were carried out on faecal specimens from 873 gastroenteritis outbreaks in Victoria, Australia (2012-2014). There were 575 (66%) detected as positive for norovirus by means of ORF 1 RT-PCR and/or ORF 2 RT-PCR. Of these, 24 (4.2%) were GII.6 (ORF 2) outbreaks, 7 (1.2%) were GII.7 (ORF 2) outbreaks, and 1 outbreak (0.2%) involved both GII.6 (ORF 2) and GII.7 (ORF 2) noroviruses. The median age of patients identified with GII.6 (ORF 2) (84 years) was significantly different from that of patients identified with GII.7 (ORF 2) (39 years). ORF 2 GII.6 and ORF 2 GII.7 sequences were always associated with a GII.P7 ORF 1 sequence, and GII.P7 sequences fell into two clusters, with one corresponding to the GII.6 ORF 2 genotype and the other to the GII.7 ORF 2 genotype, thereby indicating that the ORF 1 has been evolving separately for the two viruses. Thus, two closely related noroviruses can have a markedly different incidence and epidemiology.
Intervirology 2016;59:60-65

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The contribution of inferior colliculus activity to the auditory brainstem response (ABR) in mice

Publication date: Available online 22 August 2016
Source:Hearing Research
Author(s): Rüdiger Land, Alice Burghard, Andrej Kral
In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click-evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P0 with peak latency 7-8 ms when recorded with adequate band-pass filtering. Wave P0 showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P0 in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV.



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The contribution of inferior colliculus activity to the auditory brainstem response (ABR) in mice

Publication date: Available online 22 August 2016
Source:Hearing Research
Author(s): Rüdiger Land, Alice Burghard, Andrej Kral
In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click-evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P0 with peak latency 7-8 ms when recorded with adequate band-pass filtering. Wave P0 showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P0 in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV.



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The contribution of inferior colliculus activity to the auditory brainstem response (ABR) in mice

Publication date: Available online 22 August 2016
Source:Hearing Research
Author(s): Rüdiger Land, Alice Burghard, Andrej Kral
In mice, the auditory brainstem response (ABR) is frequently used to assess hearing status in transgenic hearing models. The diagnostic value of the ABR depends on knowledge about the anatomical sources of its characteristic waves. Here, we studied the contribution of the inferior colliculus (IC) to the click-evoked scalp ABR in mice. We demonstrate a non-invasive correlate of the IC response that can be measured in the scalp ABR as a slow positive wave P0 with peak latency 7-8 ms when recorded with adequate band-pass filtering. Wave P0 showed close correspondence in latency, magnitude and shape with the sustained part of evoked spiking activity and local field potentials (LFP) in the central nucleus of the IC. In addition, the onset peaks of the IC response were related temporally to ABR wave V and to some extent to wave IV. This relation was further supported by depth-dependent modulation of the shape of ABR wave IV and V within the IC suggesting generation within or in close vicinity to the IC. In conclusion, the slow ABR wave P0 in the scalp ABR may represent a complementary non-invasive marker for IC activity in the mouse. Further, the latency of synchronized click-evoked activity in the IC supports the view that IC contributes to ABR wave V, and possibly also to ABR wave IV.



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Effect of Contralateral Medial Olivocochlear Feedback on Perceptual Estimates of Cochlear Gain and Compression

Abstract

The active cochlear mechanism amplifies responses to low-intensity sounds, compresses the range of input sound intensities to a smaller output range, and increases cochlear frequency selectivity. The gain of the active mechanism can be modulated by the medial olivocochlear (MOC) efferent system, creating the possibility of top-down control at the earliest level of auditory processing. In humans, MOC function has mostly been measured by the suppression of otoacoustic emissions (OAEs), typically as a result of MOC activation by a contralateral elicitor sound. The exact relationship between OAE suppression and cochlear gain reduction, however, remains unclear. Here, we measured the effect of a contralateral MOC elicitor on perceptual estimates of cochlear gain and compression, obtained using the established temporal masking curve (TMC) method. The measurements were taken at a signal frequency of 2 kHz and compared with measurements of click-evoked OAE suppression. The elicitor was a broadband noise, set to a sound pressure level of 54 dB to avoid triggering the middle ear muscle reflex. Despite its low level, the elicitor had a significant effect on the TMCs, consistent with a reduction in cochlear gain. The amount of gain reduction was estimated as 4.4 dB on average, corresponding to around 18 % of the without-elicitor gain. As a result, the compression exponent increased from 0.18 to 0.27.

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