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Sökning: WFRF:(Holmberg Marcus)

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1.
  • Maier, Hannes, et al. (författare)
  • Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
  • 2022
  • Ingår i: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
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2.
  • Apró, William, et al. (författare)
  • Amino Acid-induced S6K1 Activity In Human Skeletal Muscle Is Mediated By Increased mTor/Rheb Interaction : 128 June 1, 11: 15 AM - 11: 30 AM.
  • 2016
  • Ingår i: Medicine And Science In Sports And Exercise 2016 May; Vol. 48 (5S Suppl 1), pp. 17.. - : Ovid Technologies (Wolters Kluwer Health). ; 48:5 Suppl 1, s. 17-
  • Konferensbidrag (refereegranskat)abstract
    • Cell culture studies have shown that amino acids activate mTORC1 signaling by increasing the interaction between mTOR and its essential activator Rheb. However, the existence of this mechanism in human skeletal muscle remains to be determined.PURPOSE: To determine if increased mTORC1 signaling in response to amino acids in human skeletal muscle is due to an increased interaction between mTOR and Rheb.METHODS: Eight well trained men performed resistance exercise on two separate occasions. In connection with the exercise, subjects were supplemented with flavored water (Pla) and essential amino acids (EAA) in a double-blind, randomized cross-over design. Muscle biopsies were taken in the vastus lateralis muscle before, immediately after and 90 and 180 min post exercise. Activity of the mTORC1 pathway was assessed by a radiolabeled in-vitro kinase assay for its immediate downstream target S6K1. Protein-protein interactions were determined by western blot following co-immunoprecipitation of mTOR with Rheb. Co-immunoprecipitation was performed on pooled muscle samples from three of the eight subjects.RESULTS: Activity of S6K1 remained unchanged immediately after exercise in both trials. However, at 90 min post exercise, S6K1 activity increased by approximately 2- and 8-fold (p<0.05) from baseline the Pla and EAA trials, respectively. At the 180 min time point, S6K1 activity remained elevated in both trials being approx. 3-fold higher in the Pla trial and 5-fold higher (p<0.05) in the EAA trial. The fold-change in mTOR and Rheb interaction largely resembled the activity pattern of S6K1 in both trials; in the Pla trial the fold-change was 0.9, 1.3 and 1.4 while in the EAA trial the fold-change was 1.6, 2.9 and 1.9 immediately after, 90 min after and 180 min after exercise, respectively.CONCLUSIONS: The large increase in S6K1 activity following EAA intake appears to be mediated by an increased interaction between mTOR and its proximal activator Rheb. This is the first time this mechanism has been demonstrated in human skeletal muscle.
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  • Apró, William, et al. (författare)
  • Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise
  • 2015
  • Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:10, s. 4358-4373
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids (EAAs). Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied EAAs with leucine, EAAs without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation similar to 280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAAs and does not appear to be caused by alterations inmTORC1 assembly.
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  • Apró, William, et al. (författare)
  • Resistance exercise induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high intensity interval cycling.
  • 2015
  • Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 308:6, s. E470-E481
  • Tidskriftsartikel (refereegranskat)abstract
    • Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in a randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (~90%, P<0.05) but was unchanged in R. Thr389 phosphorylation of S6K1 was increased several-fold immediately after exercise (P<0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (~55% and ~110%, respectively, P<0.05) and eEF2 phosphorylation was reduced (~55%, P<0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P<0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTORC1 signaling after subsequent resistance exercise, but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.
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7.
  • Bergengren, Oskar, et al. (författare)
  • Variation in Prostate-Specific Antigen Testing Rates and Prostate Cancer Treatments and Outcomes in a National 20-Year Cohort
  • 2021
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:5
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The diagnostic activity for prostate cancer has increased during the past decades. However, the benefit and harm of the increased diagnostic activity have not been quantified in detail for a country or a large region.OBJECTIVE: The aim of this study was to evaluate and quantify the association between increases in diagnostic activity driven by prostate-specific antigen testing and incidence of prostate cancer diagnosis, treatment, and mortality.DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Proxy-Based Risk-Stratified Incidence Simulation Model-Prostate Cancer to examine observed data on all Swedish men with prevalent prostate cancer and compare them with a corresponding, hypothetical, simulated scenario with more restrictive diagnostic activity. All men aged 40 to 100 years living in Sweden during the time period 1996 to 2016 with incident and prevalent prostate cancer were included. The second scenario is the corresponding, hypothetical, simulated scenario where diagnostic activity remained constant as of 1996 (the beginning of the prostate-specific antigen testing era) throughout the study period.EXPOSURES: High or low diagnostic activity for prostate cancer.MAIN OUTCOMES AND MEASURES: Incidence of prostate cancer diagnosis, treatment (deferred treatment, curative treatment, and hormonal treatment), and prostate cancer mortality.RESULTS: During the study period from 1996 to 2016, 188 884 men were diagnosed with prostate cancer at a median (interquartile range) age of 71 (64-77) years. Compared with the low-diagnostic activity scenario, in the high-diagnostic activity scenario, the number of men diagnosed with prostate cancer was 48% higher (423 vs 286 [95% CI, 271-302] per 100 000 men per year), 148% more men were diagnosed with low- or intermediate-risk cancer (221 vs 89 [95% CI, 73-105] per 100 000 men per year), and 108% more men received curative treatment (152 vs 73 [95% CI: 66-85] per 100 000 men per year). There were up to 15% fewer prostate cancer deaths in the scenario with high-diagnostic activity (incidence rate ratio, 0.85; 95% CI, 0.82-0.88).CONCLUSIONS AND RELEVANCE: This studys results suggest that increased prostate-specific antigen testing and diagnostic activity are associated with a larger number of men being diagnosed with prostate cancer, predominately with low- and intermediate-risk disease. The increased diagnostic activity was associated with a 2-fold increase in curative treatment and a modest decrease in mortality.
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8.
  • Bianchi, Federica, et al. (författare)
  • Benefit of Higher Maximum Force Output on Listening Effort in Bone-Anchored Hearing System Users: A Pupillometry Study
  • 2019
  • Ingår i: Ear and Hearing. - : LIPPINCOTT WILLIAMS & WILKINS. - 0196-0202 .- 1538-4667. ; 40:5, s. 1220-1232
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of this study was to compare listening effort, as estimated via pupillary response, during a speech-in-noise test in bone-anchored hearing system (BAHS) users wearing three different sound processors. The three processors, Ponto Pro (PP), Ponto 3 (P3), and Ponto 3 SuperPower (P3SP), differ in terms of maximum force output (MFO) and MFO algorithm. The hypothesis was that listeners would allocate lower listening effort with the P3SP than with the PP, as a consequence of a higher MFO and, hence, fewer saturation artifacts in the signal. Design: Pupil dilations were recorded in 21 BAHS users with a conductive or mixed hearing loss, during a speech-in-noise test performed at positive signal-to-noise ratios (SNRs), where the speech and noise levels were individually adjusted to lead to 95% correct intelligibility with the PP. The listeners had to listen to a sentence in noise, retain it for 3 seconds and then repeat it, while an eye-tracking camera recorded their pupil dilation. The three sound processors were tested in random order with a single-blinded experimental design. Two conditions were performed at the same SNR: Condition 1, where the speech level was designed to saturate the PP but not the P3SP, and condition 2, where the overall sound level was decreased relative to condition 1 to reduce saturation artifacts. Results: The P3SP led to higher speech intelligibility than the PP in both conditions, while the performance with the P3 did not differ from the performance with the PP and the P3SP. Pupil dilations were analyzed in terms of both peak pupil dilation (PPD) and overall pupil dilation via growth curve analysis (GCA). In condition 1, a significantly lower PPD, indicating a decrease in listening effort, was obtained with the P3SP relative to the PP. The PPD obtained with the P3 did not differ from the PPD obtained with the other two sound processors. In condition 2, no difference in PPD was observed across the three processors. The GCA revealed that the overall pupil dilation was significantly lower, in both conditions, with both the P3SP and the P3 relative to the PP, and, in condition 1, also with the P3SP relative to the P3. Conclusions: The overall effort to process a moderate to loud speech signal was significantly reduced by using a sound processor with a higher MFO (P3SP and P3), as a consequence of fewer saturation artifacts. These findings suggest that sound processors with a higher MFO may help BAHS users in their everyday listening scenarios, in particular in noisy environments, by improving sound quality and, thus, decreasing the amount of cognitive resources utilized to process incoming speech sounds.
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9.
  • Calon, Tim G A, et al. (författare)
  • Minimally Invasive Ponto Surgery compared to the linear incision technique without soft tissue reduction for bone conduction hearing implants: study protocol for a randomized controlled trial.
  • 2016
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the last years, less invasive surgical techniques with soft tissue preservation for bone conduction hearing implants (BCHI) have been introduced such as the linear incision technique combined with a punch. Results using this technique seem favorable in terms of rate of peri-abutment dermatitis (PAD), esthetics, and preservation of skin sensibility. Recently, a new standardized surgical technique for BCHI placement, the Minimally Invasive Ponto Surgery (MIPS) technique has been developed by Oticon Medical AB (Askim, Sweden). This technique aims to standardize surgery by using a novel surgical instrumentation kit and minimize soft tissue trauma.A multicenter randomized controlled trial is designed to compare the MIPS technique to the linear incision technique with soft tissue preservation. The primary investigation center is Maastricht University Medical Center. Sixty-two participants will be included with a 2-year follow-up period. Parameters are introduced to quantify factors such as loss of skin sensibility, dehiscence of the skin next to the abutment, skin overgrowth, and cosmetic results. A new type of sampling method is incorporated to aid in the estimation of complications. To gain further understanding of PAD, swabs and skin biopsies are collected during follow-up visits for evaluation of the bacterial profile and inflammatory cytokine expression. The primary objective of the study is to compare the incidence of PAD during the first 3 months after BCHI placement. Secondary objectives include the assessment of parameters related to surgery, wound healing, pain, loss of sensibility of the skin around the implant, implant extrusion rate, implant stability measurements, dehiscence of the skin next to the abutment, and esthetic appeal. Tertiary objectives include assessment of other factors related to PAD and a health economic evaluation.This is the first trial to compare the recently developed MIPS technique to the linear incision technique with soft tissue preservation for BCHI surgery. Newly introduced parameters and sampling method will aid in the prediction of results and complications after BCHI placement.Registered at the CCMO register in the Netherlands on 24 November 2014: NL50072.068.14 . Retrospectively registered on 21 April 2015 at ClinicalTrials.gov: NCT02438618 . This trial is sponsored by Oticon Medical AB.
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10.
  • Dermentzis, Georgios, et al. (författare)
  • Evaluation of a versatile energy auditing tool
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • Energy auditing can be an important contribution for identification and assessment of energy conservation measures (ECMs) in buildings. Numerous tools and software have been developed, with varying degree of precision and complexity and different areas of use. This paper evaluates PHPP as a versatile, easy-to-use energy auditing tool and gives examples of how it has been compared to a dynamic simulation tool, within the EU-project iNSPiRe. PHPP is a monthly balance energy calculation tool based on EN13790. It is intended for assisting the design of Passive Houses and energy renovation projects and as guidance in the choice of appropriate ECMs. PHPP was compared against the transient simulation software TRNSYS for a single family house and a multi-family house. It should be mentioned that dynamic building simulations might strongly depend on the model assumptions and simplifications compared to reality, such as ideal heating or real heat emission system. Setting common boundary conditions for both PHPP and TRNSYS, the ideal heating and cooling loads and demands were compared on monthly and annual basis for seven European locations and buildings with different floor area, S/V ratio, U-values and glazed area of the external walls. The results show that PHPP can be used to assess the heating demand of single-zone buildings and the reduction of heating demand with ECMs with good precision. The estimation of cooling demand is also acceptable if an appropriate shading factor is applied in PHPP. In general, PHPP intentionally overestimates heating and cooling loads, to be on the safe side for system sizing. Overall, the agreement with TRNSYS is better in cases with higher quality of the envelope as in cold climates and for good energy standards. As an energy auditing tool intended for pre-design it is a good, versatile and easy-to-use alternative to more complex simulation tools.
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