Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) virus in a child in Shandong Province, China.

BACKGROUND: Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. METHODS: Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. RESULTS: RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). CONCLUSIONS: The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Teaching Old Polymers New Tricks: Improved Synthesis and Anomalous Crystallinity for a Lost Semi-Fluorinated Polyaryl Ether via Interfacial Polymerization of Hexafluoroacetone Hydrate and Diphenyl Ether.

A practical and direct electrophilic polymerization of hexafluoroacetone hydrate with diphenyl ether toward the preparation of semi-fluorinated polyaryl ethers (PAE) is reported. Electrophilic aromatic substitution (EAS) polymerization under interfacial conditions with phase transfer catalyst (Aliquat 336) proceeds in trifluoromethanesulfonic anhydride by generation of trifluoromethanesulfonic acid and the protonated hexafluoroacetone (HFA) in situ affording 1,1,1,3,3,3-hexafluoroisopropylidene (6F) PAE with high regioselectivity (4,4'-DPE) and high molecular weight (≈60 kDa). Although first reported in a 1966 US Patent by DuPont using harsh conditions, improved synthetic methods or modern characterization has not been disclosed until now. Despite the presence of the 6F group, known to impart disordered morphology, this simple semi-fluorinated PAE exhibits anomalous crystallinity with polymorphic melting points (Tm ) ranging from 230-309 °C, high solubility in common organic solvents, a glass transition (Tg ) of 163 °C, and thermo-oxidative stability above 500 °C. Tough optically clear films prepared from solution give transmittance higher than 90% throughout the visible region. Synthesis, mechanistic aspects, and characterization including surface and dielectric properties are discussed.

Bilateral inferior petrosal sinus sampling: validity, diagnostic accuracy in lateralization of pituitary microadenoma, and treatment in eleven patients with Cushing's syndrome - a single-center retrospective cohort study.

BACKGROUND: This single-center retrospective cohort study aimed to describe the findings and validity of Bilateral inferior petrosal sinus sampling (BIPSS) in the differential diagnosis of patients with ACTH-dependent Cushing's syndrome (CS). METHODS: Eleven patients underwent BIPSS due to equivocal biochemical tests and imaging results. Blood samples were taken from the right inferior petrosal sinus (IPS), left IPS, and a peripheral vein before and after stimulation with desmopressin (DDAVP). ACTH and prolactin levels were measured. The diagnosis was based on the ACTH ratio between the IPS and the peripheral vein. Also, lateralization of pituitary adenoma in patients with Cushing's disease (CD) was predicted. No significant complications were observed with BIPSS. RESULTS: Based on the pathology report, eight patients had CD, and three had ectopic ACTH syndrome (EAS). Unstimulated BIPSS resulted in a sensitivity of 87.5%, specificity of 100%, PPV of 100%, NPV of 75%, and accuracy of 91%. Stimulated BIPSS resulted in a sensitivity of 100%, specificity of 100%, PPV of 100%, NPV of 100%, and accuracy of 100%. However, pituitary magnetic resonance imaging (MRI) had a lower diagnostic accuracy (sensitivity:62.5%, specificity:33%, PPV:71%, NPV:25%, accuracy:54%). BIPSS accurately demonstrated pituitary adenoma lateralization in 75% of patients with CD. CONCLUSIONS: This study suggests that BIPSS may be a reliable and low-complication technique in evaluating patients with ACTH-dependent CS who had inconclusive imaging and biochemical test results. The diagnostic accuracy is improved by DDAVP stimulation. Pituitary adenoma lateralization can be predicted with the aid of BIPSS.

Nonsinusoidalin situelectric field caused by magnetic deactivator device for EAS labels-assessment of field strength inside a detailed anatomical hand model.

In order to evaluate the localised magnetic field (MF) exposure of the cashier's hand due to a particular demagnetization device (deactivator) for single-use labels of an acoustomagnetic (AM) electronic article surveillance (EAS) system, comprehensive measurements of the MF near the surface of the deactivator, and numerical computations of the induced electric field strengthEi, were performed in high-resolution anatomical hand models of different postures and positions with respect to the deactivator. The measurement results for magnetic inductionBwere assessed with respect to the action levels (AL) for limb exposure, and the computational results forEiwere evaluated with respect to the exposure limit values (ELV) for health effects according to European Union (EU) directive 2013/35/EU. For the ELV-based assessment, a maximum of the 2 × 2 × 2 mm3averagedEi(maxEi,avg) and the respective 99.9th, 99.5th, and 99.0th percentiles were used. As the MF impulse emitted by the deactivator for demagnetization of the AM-EAS labels was highly nonsinusoidal, measurement results were assessed based on the weighted peak method in the time domain (WPM-TD). A newly developed scaling technique was proposed to also apply the WPM-TD to the assessment of the (nonsinusoidal)Eiregarding the ELV. It was used to calculate the resulting WPM-TD-based exposure index (EI) from frequency domain computations. The assessment regarding the AL for limbs yielded peak values of magnetic induction of up to 97 mT (measured with a 3 cm2MF probe on top of the deactivator surface) corresponding to an EI of 443%. However, this was considered an overestimation of the actual exposure in terms ofEias the AL were intentionally defined conservatively. A WPM-TD-based assessment ofEifinally led to the worst case EI of up to 135%, 93%, 78%, and 72% when using the maxEi,avg, 99.9th, 99.5th, and 99.0th percentiles, respectively.

Search for familial hypercholesterolemia patients in an Italian community: A real-life retrospective study.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disorder of low-density lipoprotein (LDL) catabolism that causes elevated LDL-cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Despite the availability of effective treatments, FH remains underdiagnosed and undertreated. The aims of the study were to identify putative FH subjects using data from laboratory and cardiology databases, genetically characterize suspected FH patients referred to the Lipid Clinic and monitor attainment of treatment goals in identified patients. METHODS AND RESULTS: We retrieved the electronic health records of 221,644 individuals referred to laboratory for routine assessment and of 583 ASCVD patients (age ≤65) who underwent percutaneous transluminal coronary angioplasty (PTCA). We monitored the lipid profiles of subjects with LDL-C ≥ 250 mg/dl identified by laboratory survey (LS-P), PTCA patients and patients from the Lipid Clinic (LC-P). The laboratory survey identified 1.46% of subjects with LDL-C ≥ 190 mg/dl and 0.08% with LDL-C ≥ 250 mg/dl. Probable/definite FH was suspected in 3% of PTCA patients. Molecularly-confirmed FH was found in 44% of LC-P subjects. Five new LDLR mutations were identified. The 50% LDL-C reduction target was achieved by 70.6% of LC-P patients. Only 18.5% of PTCA patients reached the LDL-C < 55 mg/dl target. CONCLUSION: By using a combined approach based on laboratory lipid profiles, documented ASCVD and Lipid Clinic data, we were able to identify subjects with a high probability of being FH. Attainment of LDL-C goals was largely suboptimal. Efforts are needed to improve FH detection and achievement of lipid targets.

Application of bulbocavernosus reflex combined with anal sphincter electromyography in the diagnosis of MSA and PD.

BACKGROUND: Multiple system atrophy (MSA) and Parkinson's disease (PD) are characterized by abnormal changes in the extrapyramidal system and autonomic nervous system. The two diseases are consistent in some clinical manifestations and few objective indicators for preclinical prediction. METHOD: The value of anal sphincter electromyography (EAS-EMG) in the diagnosis of MSA has been recognized by researchers, while the bulbocavernosus reflex (BCR) has been found to be of great significance in the diagnosis of PD and MSA. In this study, the diagnostic value of BCR combined with EAS-EMG in patients with MSA and PD was further discussed. RESULTS: Forty-three patients with MSA, 120 patients with PD and 40 normal controls were recruited, and the BCR and EAS-EMG were evaluated. The average duration, average amplitude, percentage of polyphasic waves, satellite potential, phase pattern and amplitude of strong contraction were observed. The results showed that the abnormal rate of BCR in the control group was 0%, and the abnormal rate of EAS-EMG was 2.5%; these differences were statistically significant compared with the MSA group (BCR 90.9%, EAS-EMG 93.9%). For patients with PD, there were some significant differences in BCR and EAS-EMG between the control group and the PD group. CONCLUSION: Our study revealed that BCR combined with EAS-EMG detection can provide an objective electrophysiological basis for the diagnosis of MSA and PD, which is beneficial for the early treatment of disease.

Searching for the Molecular Basis of Partial Deafness.

Hearing is an important human sense for communicating and connecting with others. Partial deafness (PD) is a common hearing problem, in which there is a down-sloping audiogram. In this study, we apply a practical system for classifying PD patients, used for treatment purposes, to distinguish two groups of patients: one with almost normal hearing thresholds at low frequencies (PDT-EC, n = 20), and a second group with poorer thresholds at those same low frequencies (PDT-EAS, n = 20). After performing comprehensive genetic testing with a panel of 237 genes, we found that genetic factors can explain a significant proportion of both PDT-EC and PDT-EAS hearing losses, accounting, respectively, for approx. one-fifth and one-half of all the cases in our cohort. Most of the causative variants were located in dominant and recessive genes previously linked to PD, but more than half of the variants were novel. Among the contributors to PDT-EC we identified OSBPL2 and SYNE4, two relatively new hereditary hearing loss genes with a low publication profile. Our study revealed that, for all PD patients, a postlingual hearing loss more severe in the low-frequency range is associated with a higher detection rate of causative variants. Isolating a genetic cause of PD is important in terms of prognosis, therapeutic effectiveness, and risk of recurrence.

Head-to-head comparison of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in localizing tumors with ectopic adrenocorticotropic hormone secretion: a prospective study.

PURPOSE: Localizing the source of ectopic adrenocorticotropic hormone secretion (EAS) is challenging. This study compared the diagnostic value of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in tumors with EAS. METHODS: Thirty-six patients with a suspicion of EAS were enrolled to undergo both 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT within 4 weeks for comparison. Twenty-three underwent surgical resection or biopsy. Immunohistochemical staining for SSTR2 and Ki-67 was performed to correlate with 68Ga-DOTATATE uptake and 18F-FDG uptake, respectively. RESULTS: EAS tumors were observed in 20/23 patients. Among the 20 patients with histologically proven EAS tumors, 68Ga-DOTATATE PET/CT correctly identified the tumor in 15 (75.0%), with an SUVmax ranging from 1.4 to 20.7 (6.7 ± 5.5). 18F-FDG PET/CT correctly identified the tumor in 12 (60.0%) patients, with an SUVmax ranging from 1.8 to 10.0 (4.0 ± 2.1). Moreover, 68Ga-DOTATATE PET/CT unmasked the sources of EAS in 6 patients with negative 18F-FDG uptake, and 18F-FDG PET/CT unmasked the sources in 3 patients with negative 68Ga-DOTATATE uptake, resulting in EAS tumors being identified in 18 (90%) patients by combining 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT. CONCLUSIONS: 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT are complementary in localizing and discriminating the source of EAS. 68Ga-DOTATATE PET/CT combined with 18F-FDG PET/CT had higher detection rate than each alone. TRIAL REGISTRATION: 68Ga-DOTATATE PET/CT in Neuroendocrine Tumors (NCT04041882) URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04041882.

The usefulness of the combined high-dose dexamethasone suppression test and desmopressin stimulation test in establishing the source of ACTH secretion in ACTH-dependent Cushing's syndrome.

Bilateral inferior petrosal sinus sampling (BIPSS) is the current gold standard test for differentially diagnosing ACTH-dependent Cushing's syndrome (CS). However, BIPSS is an invasive procedure, and its availability is limited. We retrospectively analysed the 24-hour urinary free cortisol (UFC) level during the high-dose dexamethasone suppression test (HDDST) and plasma ACTH/cortisol levels after the desmopressin stimulation test (DDAVP test) in subjects with confirmed Cushing's disease (CD) (n = 92) and ectopic ACTH-dependent CS (EAS) (n = 16), and evaluated the positive predictive value (PPV) of the two combined-tests in the aetiological diagnosis of ACTH-dependent CS. The percent changes in UFC levels after the HDDST and in ACTH/cortisol levels after DDAVP administration relative to the corresponding basal levels and the area under the receiver operating characteristic (ROC) curve (AUC) were analysed. UFC suppression below 62.7% suggested a pituitary origin with a sensitivity (SE) of 80% (95% CI: 70-88) and a specificity (SP) of 80% (95% CI: 52-96). A threshold increase in the ACTH level after DDAVP stimulation of 44.6% identified CD with an SE of 91% (95% CI: 83-97) and an SP of 75% (95% CI: 48-93). The combination of both tests yielded an SE of 95.5% and PPV of 98.4% for CD, and significantly improved the efficiency of the differential diagnosis between CD and EAS. These dual non-invasive endocrine tests may substantially reduce the need for BIPSS in the etiological investigation of ACTH-dependent CS.

Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study.

AIMS: To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. METHODS AND RESULTS: Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6-10 weeks after an MI event, 2013-17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target. CONCLUSION: Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.

Assessment of application of the new 2019 European Society of Cardiology/ European Atherosclerosis Society Guidelines for the Management of Dyslipidaemias in daily clinical practice - one center study.

B a c k g r o u n d: Cardiovascular diseases are the first cause of death globally. Hypercholester- olemia is the most important factor responsible for atherosclerotic plaque formation and increasing cardiovascular risk. Reduction of LDL-C level is the most relevant goal for reduction of cardiovascular risk. A i m s: Real life adherence to guidelines concerning statin therapy in one center study population. M e t h o d s: We analyzed data collected in the Department of Internal Diseases from September 2019 to February 2020, obtained from 238 patients hospitalized in this time period. We assessed application of the new 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias in daily clinical practice and compared effectiveness of LLT according to 2016 and 2019 guidelines. R e s u l t s: Only 1 in 5 patients with dyslipideamia achieve the 2019 ESC/EAS guideline-recommended levels of LDL-C with relation to their TCVR. We noticed that 20 of patients who did not achieve proper 2019 LDL level, meet new therapy targets established in year 2016. We observed that higher patient TCVR resulted in better compliance with guidelines and ordination of proper LLT. Most patients were on monotherapy with statins. C o n c l u s i o n s: It could be beneficial to start treatment with double or even triple therapy especially in group with the highest LDL-C levels.

Long-term residual hearing in cochlear implanted adult patients who were candidates for electro-acoustic stimulation.

PURPOSE: To evaluate the long-term hearing outcomes in cochlear implanted adults with residual hearing at low frequencies, and the proportion of patients using electro-acoustic stimulation (EAS). METHODS: A monocentric retrospective cohort study was performed in a tertiary referral center. Population demographics, surgical approach, pre- and postoperative hearing at low frequencies, in the implanted and contralateral ear, were recorded as well as duration of EAS use. The percentage hearing preservation was calculated according to the formula S (HEARRING group). RESULTS: In total, 63 adults (81 ears) with residual hearing underwent cochlear implantation with intent to use EAS processors. Six different types of electrode array were implanted. The mean pure tone audiometry (PTA) shift after cochlear implantation was 16 ± 15 dB HL (range 0-59 dB HL). Half of the implanted ears had minimal hearing preservation or total hearing loss (HL) at 5.5 years and the cumulative risk of total HL was 50% at 7 years. During the follow-up, total HL occurred in 22 ears. The decrease in hearing levels was similar in both implanted and contralateral ear during follow-up (ns, F = 2.46 ± 3, Linear Mixed Model (LMM)). Only 44 patients found a benefit from EAS at the first fitting. At the last visit, EAS processors were fitted in 30% of the cases. The pre- and postoperative mean PTA thresholds were not predictive of EAS use (Cox's proportional hazards analysis). CONCLUSIONS: Postoperative residual hearing was observed in 93% of implanted ears, but only half of them had an initial benefit from EAS. No predictive factors were found to influence the use of EAS processors.

An ERF2-like transcription factor regulates production of the defense sesquiterpene capsidiol upon Alternaria alternata infection.

Capsidiol is a sesquiterpenoid phytoalexin produced in Nicotiana and Capsicum species in response to pathogen attack. Whether capsidiol plays a defensive role and how its biosynthesis is regulated in the wild tobacco Nicotiana attenuata when the plant is attacked by Alternaria alternata (tobacco pathotype), a notorious necrotrophic fungus causing brown spot disease, are unknown. Transcriptome analysis indicated that a metabolic switch to sesquiterpene biosynthesis occurred in young leaves of N. attenuata after A. alternata inoculation: many genes leading to sesquiterpene production were strongly up-regulated, including the capsidiol biosynthetic genes 5-epi-aristolochene synthase (EAS) and 5-epi-aristolochene hydroxylase (EAH). Consistently, the level of capsidiol was increased dramatically in young leaves after fungal inoculation, from not detectable in mock control to 50.68±3.10 µg g-1 fresh leaf at 3 d post-inoculation. Capsidiol-reduced or capsidiol-depleted plants, which were generated by silencing EAHs or EASs by virus-induced gene silencing, were more susceptible to the fungus. In addition, this sesquiterpene when purified from infected plants exhibited strong anti-fungal activities against A. alternata in vitro. Furthermore, an ERF2-like transcription factor was found to positively regulate capsidiol production and plant resistance through the direct transactivation of a capsidiol biosynthetic gene, EAS12. Taken together, our results demonstrate that capsidiol, a phytoalexin highly accumulated in N. attenuata plants in response to A. alternata infection, plays an important role in pathogen resistance independent of jasmonate and ethylene signaling pathways, and its biosynthesis is transcriptionally regulated by an ERF2-like transcription factor.

Molecular Docking and Molecular Dynamics (MD) Simulation of Human Anti-Complement Factor H (CFH) Antibody Ab42 and CFH Polypeptide.

An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. An autoantibody to CHF is associated with anti-tumor cell activity. The interaction of a human monoclonal antibody Ab42 that was isolated from a cancer patient with CFH polypeptide (pCFH) antigen was analyzed by molecular docking, molecular dynamics (MD) simulation, free energy calculation, and computational alanine scanning (CAS). Experimental alanine scanning (EAS) was then carried out to verify the results of the theoretical calculation. Our results demonstrated that the Ab42 antibody interacts with pCFH by hydrogen bonds through the Tyr315, Ser100, Gly33, and Tyr53 residues on the complementarity-determining regions (CDRs), respectively, with the amino acid residues of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448 on the pCFH antigen. In conclusion, this study has explored the mechanism of interaction between Ab42 antibody and its targeted antigen by both theoretical and experimental analysis. Our results have important theoretical significance for the design and development of relevant antibody drugs.

A summary of the EAS consensus concerning the causal relationship between low-density lipoproteins and atherosclerotic cardiovascular diseases, prepared by the Board of the Czech Society for Atherosclerosis.

This article summarised opinion of the European Society for Atherosclerosis on the causal relationship between low density lipoprotein (LDL) and the development of atherosclerosis. The fact that there is a clear causal relationship between the LDL concentration and the development of atherosclerotic cardiovascular disease (ASKVO) is evidenced by congenital lipid metabolism disorders and results of prospective epidemiological studies, Mendelian randomized trials, and randomized controlled trials. It is documented that the effect of LDL exposure on ASKVO development is cumulative; the additive effect of other risk factors is also discussed. In conclusion the facts, underlying the rational approach to the therapy of patients with dyslipidemia, are summarized. Key words: atherosclerotic cardiovascular disease - LDL - low density lipoprotein - EAS.

Evaluation of anatomical and functional results of overlapping anal sphincter repair with or without the injection of bone marrow aspirate concentrate: a case-control study.

AIM: Overlapping anal sphincter repair (OASR) is used for treatment of faecal incontinence due to an external anal sphincter (EAS) defect; however, it is not the optimal treatment as its functional results tend to deteriorate significantly with time. The present study aimed to evaluate the effect of local injection of bone marrow aspirate concentrate (BMAC) on the outcome of OASR. METHOD: We compared a prospective group of 20 patients with EAS defect who were managed with OASR and BMAC injection (group I) with a historical control group of an equal number of patients managed with OASR alone (group II). Patients were assessed preoperatively and during follow-up by the Wexner continence score and endoanal ultrasound. The primary end-points were the improvement of the continence level measured by the Wexner score and the residual EAS defect size measured by endoanal ultrasound. RESULTS: At the end of follow-up, group I had significantly lower mean postoperative Wexner score (5.4 ± 7.6 vs 10.6 ± 7.4; P = 0.03) and smaller EAS defect percentage (12.2 ± 17.5 vs 18.3 ± 18.9). These findings were statistically significant in patients with a small preoperative EAS defect equal to or less than one-third of the anal circumference. Patients with larger preoperative EAS did not show a significant improvement of the continence level after repair in either group. CONCLUSION: Augmenting OASR with local injection of BMAC in patients with faecal incontinence caused by an EAS defect, particularly a smaller defect, can improve both functional and anatomical outcomes of OASR.

Determination of optimal excitation patterns for local mechanical inner ear stimulation using a physiologically-based model.

Within the field of hearing prosthetics it is known that patients with sufficient residual hearing benefit from the simultaneous employment of hearing aid and cochlear implant. Several attempts have been proposed to combine the sources of the corresponding acoustic and electric stimuli in a single, implantable device. However, since only little is known about the effect of also applying the acoustic stimulus locally from within the inner ear, the current state of research lacks detailed knowledge on the optimal stimulation at the corresponding bionic interface. Within this manuscript, a simple but yet physiologically-based inner ear model is presented which was designed specifically for the analysis of local acoustic or mechanical inner ear stimulation. A detailed model analysis is performed showing that it is capable of mirroring the known mechanical phenomena of this particular stimulation approach. Using the model, it is demonstrated how amplitude and phase shift values of stimuli applied from within the inner ear should be chosen for optimal inner ear stimulation.

Additional Prognostic Value of EAS index in predicting the occurrence of rehospitalizations in chronic heart failure: data from the Daunia Heart Failure Registry.

BACKGROUND: Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of newly developed TDI parameters, however, still needs to be documented. METHODS: A total of 287 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a median 255 (204-316) days. Conventional echocardiography and TDI parameters were calculated. We also quantified by TDI a combined index (EAS index) of diastolic and systolic performance E'/(A'xS') and assessed its possible additional prognostic role in combination with 'traditional' parameters such as left ventricular ejection fraction (LVEF) and myocardial performance index (MPI). RESULTS: Subjects readmitted for worsening HF were characterized by higher levels of EAS index (median 0·14 (95% C.I. 0·12-0·21) vs. 0·11 (0·10-0·12, P < 0·05)). Increased rates of rehospitalization were found in subjects with EAS index >median (0·115) (21% vs. 10%, P < 0·05); higher EAS index values predicted the incidence of readmissions for worsening HF during follow-up, even at multivariable analysis. The assessment of EAS index in addition to LVEF and MPI showed an adjunctive prognostic value (log-rank P < 0·001 and P < 0·05, respectively). CONCLUSIONS: EAS index assessed by TDI may be helpful in predicting the risk of rehospitalizations in subjects with CHF. EAS index may represent an independent adjunctive tool for the risk stratification of patients with CHF in addition to 'traditional' tools such as LVEF or MPI.

Intake of total and added sugars and nutrient dilution in Australian children and adolescents.

This analysis aimed to examine the association between intake of sugars (total or added) and nutrient intake with data from a recent Australian national nutrition survey, the 2007 Australian National Children's Nutrition and Physical Activity Survey (2007ANCNPAS). Data from participants (n 4140; 51 % male) who provided 2×plausible 24-h recalls were included in the analysis. The values on added sugars for foods were estimated using a previously published ten-step systematic methodology. Reported intakes of nutrients and foods defined in the 2007ANCNPAS were analysed by age- and sex-specific quintiles of %energy from added sugars (%EAS) or %energy from total sugars (%ETS) using ANCOVA. Linear trends across the quintiles were examined using multiple linear regression. Logistic regression analysis was used to calculate the OR of not meeting a specified nutrient reference values for Australia and New Zealand per unit in %EAS or %ETS. Analyses were adjusted for age, sex, BMI z-score and total energy intake. Small but significant negative associations were seen between %EAS and the intakes of most nutrient intakes (all P<0·001). For %ETS the associations with nutrient intakes were inconsistent; even then they were smaller than that for %EAS. In general, higher intakes of added sugars were associated with lower intakes of most nutrient-rich, 'core' food groups and higher intakes of energy-dense, nutrient-poor 'extra' foods. In conclusion, assessing intakes of added sugars may be a better approach for addressing issues of diet quality compared with intakes of total sugars.

Mutational spectrum and clinical features of patients with ACTG1 mutations identified by massively parallel DNA sequencing.

OBJECTIVES: ACTG1 has been reported to be a causative gene for autosomal dominant sensorineural hearing loss, DFNA20/26. In this study we sought to clarify the detailed mutational spectrum, clinical features, and genotype-phenotype correlations. METHODS: Massively parallel DNA sequencing (MPS) of 63 target candidate genes was used to screen 1120 Japanese hearing loss patients. RESULTS: MPS screening successfully identified 4 ACTG1 mutations in 5 families. The majority of patients showed high frequency-involved progressive hearing loss, with the age of onset mostly in the first or second decade. One patient received electric acoustic stimulation (EAS), which showed a good outcome. CONCLUSIONS: Target exon-sequencing using MPS was proven to be a powerful new clinical diagnostic tool for the identification of rare causative genes such as ACTG1. The present clinical findings not only confirmed those previous reports but also provided important new clinical information.