ABSTRACT
Surgical interventions, like barbed reposition pharyngoplasty (BRP), are a valuable alternative for patients with obstructive sleep apnea (OSA) who are unable to tolerate continuous positive airway pressure (CPAP). However, predicting surgical success remains challenging, partly due to the contribution of non-anatomical factors. Therefore, combined medical treatment with acetazolamide, known to stabilize respiratory drive, may lead to superior surgical results. This double-blind, parallel-group randomized controlled trial evaluates the efficacy of acetazolamide as an add-on therapy to BRP in OSA. A total of 26 patients with moderate to severe OSA undergoing BRP were randomized to receive either acetazolamide or placebo post-surgery for 16 weeks. The group who was treated with BRP in combination with acetazolamide showed a reduction in AHI of 69.4%, significantly surpassing the 32.7% reduction of the BRP + placebo group (p < 0.01). The sleep apnea-specific hypoxic burden also decreased significantly in the group who was treated with BRP + acetazolamide (p < 0.01), but not in the group receiving BRP + placebo (p = 0.28). Based on these results, acetazolamide as an add-on therapy following BRP surgery shows promise in improving outcomes for OSA patients, addressing both anatomical and non-anatomical factors.
ABSTRACT
Obstructive sleep apnea (OSA) is a sleep disorder characterized by repetitive episodes of partial or complete obstruction of the upper airway during sleep. Continuous positive airway pressure (CPAP) is a method used as a first-line treatment for obstructive sleep apnea (OSA). However, intolerance and resistance to CPAP can limit its long-term effectiveness. Alternative treatments are available, such as Mandibular Advancement Devices (MADs), positional therapy, upper airway surgery, and maxillomandibular osteotomy. However, often less efficient in reducing the apnea-hypopnea index, the higher tolerance of and compliance to alternative treatment has resulted in the adequate treatment of OSA in CPAP-intolerant patients. This paper describes the protocol of a prospective single-center cohort study including adult patients with moderate to severe OSA (15 events/h ≤ apnea-hypopnea index (AHI) < 65 events/h) that failed to comply with CPAP therapy. Selected patients will be invited to the clinic to explore alternative treatment options where DISE will be a first step in further identifying upper airway collapse during sleep. By exploring alternative treatment options in CPAP-intolerant patients and systematically documenting their treatment paths, an algorithm can be defined to better guide patients towards personalized treatment for OSA. The follow-up is aimed at 5 years with an inclusion of 170 patients per year, including a drop-out rate of 15%. By leveraging a real-world database, this study aims to bridge the gap between research and clinical practice, facilitating the development of evidence-based guidelines and personalized treatment algorithms for CPAP-intolerant patients.
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Hypoglossal nerve stimulation (HGNS) has emerged as a widespread and innovative treatment option for selected moderate-to-severe obstructive sleep apnea (OSA) patients who cannot be treated effectively with traditional treatment modalities. In this observational cohort study, the objective and subjective outcomes of Belgian OSA patients treated with HGNS therapy were analyzed at 6 and 12 months post-implantation. Thirty-nine patients implanted with a respiration-synchronized HGNS device at the Antwerp University Hospital w ere included in this study. Patients underwent baseline in-laboratory polysomnography and a follow-up sleep study 6 and 12 months post-implantation. Questionnaires on patient experience and daytime sleepiness were filled out and data on objective therapy usage were collected. All 39 patients completed the 6-month follow-up and 21 patients (54%) completed the 12-month follow-up. Median AHI decreased from 33.8 [26.1;45.0] to 10.2 [4.8;16.4] at the 6-month follow-up, and to 9.6 [4.1;16.4] at the 12-month follow-up (p < 0.001). The surgical success rate, according to the Sher20 criteria, was 80% and 76% at the 6- and 12-month follow-ups, respectively. Median ESS improved from 12.0 [7.0;18.0] at baseline to 6.0 [2.5;11.0] at 6 months (p < 0.001) and to 6.5 [2.8;11.5] at 12 months (p = 0.012). Objective therapy usage was 7.4 [6.6;8.0] and 7.0 [5.9:8.2] h/night at the 6- and 12-month follow-ups, respectively. A high overall clinical effectiveness of HGNS therapy, as shown by a mean disease alleviation of 58%, was demonstrated at 12 months post-implantation. Overall, HGNS therapy using respiration-synchronized neurostimulation of the XII cranial nerve resulted in a significant improvement in both objective and subjective OSA outcomes, with a high level of patient satisfaction and high treatment adherence.
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In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed. Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans "pan-transcriptome"-a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging.
Subject(s)
Aging , Caenorhabditis elegans , Gene Regulatory Networks , Longevity , Transcriptome , Caenorhabditis elegans/genetics , Caenorhabditis elegans/physiology , Animals , Aging/genetics , Transcriptome/genetics , Longevity/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , RNA, Messenger/metabolism , RNA, Messenger/geneticsSubject(s)
Peripheral Arterial Disease , Humans , Peripheral Arterial Disease/genetics , Male , Female , Middle Aged , Disease Progression , Aged , Multifactorial InheritanceABSTRACT
Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P<0.001), and mean slope of 0.95 ± 0.04. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers, with close-to-zero mean difference and without correlation between the mean and difference values (across map types, mean P value was 0.48 ± 0.27). The entire quantitative data and postprocessing scripts described in the manuscript are publicly available under dedicated GitHub and Figshare repositories. The quantitative maps produced by the presented protocol can promote longitudinal and multi-center studies, and improve the biological interpretability of qMRI by integrating multiple metrics that can reveal information, which is not apparent when examined using only a single contrast mechanism.
Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Male , Female , Image Processing, Computer-Assisted/methods , Young AdultABSTRACT
OBJECTIVES: To evaluate secondary intention wound healing in the horse's limbs when treated with the synthetic epidermis spray (Novacika®, Cohesive S.A.S, France) or with a standard bandaging technique. METHODS: Six Standardbred mares were included in the study. Four 2.5 x 2.5 cm full-thickness skin wounds were created on each thoracic limb. Two wounds were located on the dorsoproximal aspect of the cannon bone and the other two at the dorsoproximal aspect of the fetlock. Six hours after creation, wounds were randomly treated with synthetic epidermis spray or standard bandaging. The wounds were assessed every 4 days by gross visual assessment and using a 3D imaging camera. Analysis was performed with a 3D imaging application. RESULTS: Out of 46 wounds, 22 showed exuberant granulation tissue and were part of the standard bandaging group. Whether the wounds were treated with synthetic epidermis spray or standard bandaging, the time for healing was the same. CONCLUSION: The synthetic epidermis spray studied in this model has allowed healing without the production of exuberant granulation tissue but did not reduce the median wound healing time compared to a standard bandaging technique. The synthetic epidermis spray is potentially an interesting alternative for the management of secondary intention wound healing of superficial and non-infected distal limb wounds in adult horses on economical and practical aspects. However, all statistical inference (p-values especially) must be interpreted with caution, given the size of the sample.
Subject(s)
Intention , Skin Diseases , Animals , Female , Epidermis , Forelimb , Horses , Wound HealingABSTRACT
INTRODUCTION: Custom-made titratable mandibular advancement device (MAD) treatment can nowadays be considered a promising first-line treatment in patients with mild to severe obstructive sleep apnea (OSA). Specific manufacturing designs and titration mechanisms of MAD are on the market, characterized by their titration approach, vertical opening, and materials selection. The wing-designed MAD (SomnoDent® Flex™, SomnoMed Ltd, Sydney, Australia) has a lateral screw mechanism to advance the lower jaw in incremental steps of 0.1 up to 6.0 mm. The newer uniquely designed custom-made MAD with passive mouth closing (SomnoDent® Avant™ SomnoMed Ltd, Sydney, Australia) has a frontal exchangeable advancement strap of fixed lengths as a specific titration mechanism, all supporting freedom of lateral movement. We aimed to assess the associations between the type of MAD prescribed and OSA treatment outcome. METHODS: Data from 209 patients (165 male, mean age 53.9 (±10.9) years, median baseline BMI and AHI 27.02 [24.8; 29.7] kg/m2 and 22.8 [17.7; 31.6]/hour sleep, respectively) were collected. Of this cohort, 91 patients with the traditional, wing-based SomnoDent® Flex™ and 118 patients with SomnoDent® Avant™. All patients were diagnosed with a type 1 polysomnography demonstrating moderate to severe OSA (15 ≤ AHI ≤65 per hour sleep). The selected MAD was fitted in the so-called maximal comfortable protrusion. After 3 months of subjective titration until resolution of subjective symptoms and/or achieving physical limits, a checkup with validated home sleep monitoring was conducted. Treatment success was defined as "AHI reduction ≥50% with MAD compared to baseline AHI and AHI with MAD <10 events per hour". RESULTS: These real-world data set showed that 67% of patients achieved treatment success, with a statistically significant reduction in AHI from 22.8 [17.7; 31.6] to 7.45 [3.4; 15.0]/h sleep. The SomnoDent® Avant™ achieved 75% treatment success versus 56% for the traditional, wing-based SomnoDent® Flex™ (P < 0.05). Overall, AHI reduction was 70% for SomnoDent® Avant™ (P < 0.05) vs. 63% for SomnoDent® Flex™ (P < 0.05). CONCLUSIONS: This study shows that choice of MAD design can impact the treatment outcome and could become an important consideration in selecting the type of MAD for personalized treatment for OSA patients. While the results of the traditional wing-based MAD design were comparable to the therapeutic outcome with other titratable, custom-made MADs, the MAD with the passive mouth closing feature showed significantly greater reduction in total AHI potentially due to encouraged nasal breathing, reduced mouth breathing and lesser vertical opening thereby decreasing the probability of tongue base collapse.
Subject(s)
Mandibular Advancement , Sleep Apnea, Obstructive , Humans , Male , Middle Aged , Sleep Apnea, Obstructive/therapy , Occlusal Splints , Treatment Outcome , SleepABSTRACT
Lactate dehydrogenase (LDH) from Schistosoma mansoni has peculiar properties for a eukaryotic LDH. Schistosomal LDH (SmLDH) isolated from schistosomes, and the recombinantly expressed protein, are strongly inhibited by ATP, which is neutralized by fructose-1,6-bisphosphate (FBP). In the conserved FBP/anion binding site we identified two residues in SmLDH (Val187 and Tyr190) that differ from the conserved residues in LDHs of other eukaryotes, but are identical to conserved residues in FBP-sensitive prokaryotic LDHs. Three-dimensional (3D) models were generated to compare the structure of SmLDH with other LDHs. These models indicated that residues Val187, and especially Tyr190, play a crucial role in the interaction of FBP with the anion pocket of SmLDH. These 3D models of SmLDH are also consistent with a competitive model of SmLDH inhibition in which ATP (inhibitor) and FBP (activator) compete for binding in a well-defined anion pocket. The model of bound ATP predicts a distortion of the nearby key catalytic residue His195, resulting in enzyme inhibition. To investigate a possible physiological role of this allosteric regulation of LDH in schistosomes we made a kinetic model in which the allosteric regulation of the glycolytic enzymes can be varied. The model showed that inhibition of LDH by ATP prevents fermentation to lactate in the free-living stages in water and ensures complete oxidation via the Krebs cycle of the endogenous glycogen reserves. This mechanism of allosteric inhibition by ATP prevents the untimely depletion of these glycogen reserves, the only fuel of the free-living cercariae. Neutralization by FBP of this ATP inhibition of LDH prevents accumulation of glycolytic intermediates when S. mansoni schistosomula are confronted with the sudden large increase in glucose availability upon penetration of the final host. It appears that the LDH of S. mansoni is special and well suited to deal with the variations in glucose availability the parasite encounters during its life cycle.
Subject(s)
Adenosine Triphosphate , L-Lactate Dehydrogenase , Models, Molecular , Schistosoma mansoni , Schistosoma mansoni/enzymology , Schistosoma mansoni/metabolism , Animals , L-Lactate Dehydrogenase/metabolism , L-Lactate Dehydrogenase/genetics , Kinetics , Adenosine Triphosphate/metabolism , Fructosediphosphates/metabolism , Mice , Amino Acid Sequence , Biomphalaria/parasitology , Binding SitesABSTRACT
BACKGROUND: Differences in the pharyngeal site of collapse influence efficacy of non-continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site of collapse using overnight polysomnography. METHODS: 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, n=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (n=22) versus absence (n=128) of CCCp (partial collapse and concurrent tongue base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue base or epiglottis collapse. External validation was performed on a separate dataset (ntotal=466). RESULTS: CCCp was characterised by greater scoopiness (ß=1.5±0.6 per 2sd, multivariable estimate±se) and skewness (ß=11.4±2.4) compared with non-CCCp. The odds ratio for CCCp in predicted positive versus negative subgroups was 5.0 (95% CI 1.9-13.1). The same characteristics provided significant cross-validated prediction of lateral wall (OR 6.3, 95% CI 2.4-16.5), tongue base (OR 3.2, 95% CI 1.4-7.3) and epiglottis (OR 4.4, 95% CI 1.5-12.4) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue base and epiglottis collapse characteristics. External validation confirmed model prediction. CONCLUSIONS: The current study provides a means to recognise patients with likely CCCp or other DISE-based site of collapse categories using routine polysomnography. Since site of collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.
Subject(s)
Endoscopy , Polysomnography , Sleep Apnea, Obstructive , Humans , Male , Female , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/therapy , Middle Aged , Adult , Logistic Models , Sleep , Aged , Tongue/physiopathology , Pharynx/physiopathology , Hypoglossal Nerve , Multivariate Analysis , Palate , Epiglottis/physiopathology , Continuous Positive Airway PressureABSTRACT
The temporary ligation of the common carotid artery is performed as an emergency aid in cases of guttural pouch mycosis. Its usefulness is put into perspective after an anatomical summary of arterial vascularization involving a guttural pouch. It helps to better understand the need for the cranial (cerebral) and caudal (cardiac) occlusion of an arterial rupture by embolization in order to achieve maximum success in preventing and treating an hemorrhage. Topical oxygen therapy used alone or in a multimodal approach with embolization surgery is performed to promote healing of the inflammatory and mycotic lesions observed when an individual is affected. In conclusion, this three-step therapeutic approach should enable the equine practitioner to better orient their decision tree when faced with this condition which, while rare, can be potentially fatal if poorly treated.
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OBJECTIVE: To report findings, outcome and determine variables associated with survival in horses with acquired inguinal hernia (AIH). STUDY DESIGN: Retrospective study. ANIMALS: A total of 98 cases in 97 horses. METHODS: The medical records (2005-2020) of horses diagnosed with AIH were reviewed. Retrieved data included signalment, history, clinical variables, surgical aspects, postoperative complications, and short- and long-term outcomes. Logistic regression analyses were used to determine factors associated with short-term survival (p < .05). RESULTS: Manual reduction was attempted in a third of the cases (32/98, 33%) and emergency surgery to reduce the hernia was performed in 64 of 98 (65%) cases. Concurrent small intestinal (SI) volvulus was identified in 26 (26/98, 27%) cases. Castration was the most common technique used to prevent recurrence (64/94, 68%). Overall AIH recurrence rate was 11% (11/98). A total of 59 (59/98, 60%) cases survived to hospital discharge and 49 of 52 (94%) cases were still alive after 12 months. Cases admitted within 10 h of colic signs had increased odds of survival (72%) compared to those admitted after 10 h (26%; p < .001). Draft breeds (p = .021), high heart rate on admission (p = .001) and concurrent SI volvulus (p = .048) were associated with reduced survival to hospital discharge. CONCLUSIONS: Horses with AIH had a higher risk of concurrent SI volvulus and lower survival than reported. Draft breeds, high heart rate on admission and concurrent SI volvulus were associated with reduced short-term survival. CLINICAL SIGNIFICANCE: The results of this study should help in prognostication for horses with AIH.
Subject(s)
Colic , Hernia, Inguinal , Horse Diseases , Intestinal Volvulus , Animals , Horses , Hernia, Inguinal/veterinary , Intestinal Volvulus/veterinary , Prognosis , Retrospective Studies , Intestine, Small/surgery , Postoperative Complications/veterinary , Horse Diseases/surgery , Colic/veterinaryABSTRACT
PURPOSE: Recent literature suggests that tinnitus can impact cognition, but results were varied due to a diversity in investigated aspects of cognition and utilized tests, as well as the possible influence of confounding factors. The purpose of this study was to assess the impact of tinnitus loudness on cognition by use of a within-subjects design in patients with a cochlear implant (CI). In this population, tinnitus loudness can be modulated by switching the CI on or off as CI is known to highly suppress tinnitus. METHODS: A total of 18 CI users completed two versions of the Repeatable Battery for Assessment of Neuropsychological Status for Hearing Impaired individuals (RBANS-H), once in unaided condition and once in best aided condition. Tinnitus suppression was defined as a difference in score on a visual-analogue scale (VAS) of at least one point out of ten between these two conditions. RESULTS: No significant differences in RBANS-H scores were found between the suppression and no suppression group, nor for the suppression group alone. No significant correlations between tinnitus loudness and RBANS-H were found, neither for the suppression group alone, nor for the group as a whole. CONCLUSION: The current study shows no significant effect of tinnitus loudness on cognition, which contradicts previous literature. This discrepancy could be explained by the use of a within-subjects design, which controls for confounding factors. Future research should include a larger and more diverse study sample to draw definitive conclusions on this topic.
Subject(s)
Cochlear Implantation , Cochlear Implants , Tinnitus , Humans , Cochlear Implantation/methods , Tinnitus/surgery , CognitionABSTRACT
The secondary alveolar bone grafting (SABG) step restores the continuity of the alveolar bone necessary for dentition. Faced with the complications of autografts, synthetic biomaterials such as Bioglass (BG) 45S5 have been proposed. The objective was to evaluate the success rate of SABG with the addition of BG 45S5 and to highlight the prognostic factors. Patients who underwent operation between 2015 and 2021 and had follow-up cone-beam computed tomography (CBCT) were analyzed. Multivariate analysis was performed to determine factors influencing radiographic success. A total of 102 SABG were analyzed. They were unilateral total cleft lip and palate (49, 48.0%). The mean age at surgery was 9.32 ± 3.09 years. Surgeries were performed mainly outside a syndromic context and without a family history after orthodontic preparation. The radiographic success rate at 1 year was 80.4%. Mixed dentition stage (odds ratio [OR] = 7.3, p = 0.024), absence of syndromic context (OR = 20.7, p = 0.024) and female sex (OR = 4.88, p = 0.021) were factors predictive of surgical success. The use of BG 45S5 instead of autograft is relevant for SABG, with a 1-year success rate of over 80%. The stage of mixed dentition, the absence of syndromic context, and female sex were factors for good prognosis.
Subject(s)
Alveolar Bone Grafting , Ceramics , Cleft Lip , Cleft Palate , Glass , Humans , Female , Child , Cleft Lip/surgery , Retrospective Studies , Cleft Palate/surgery , Alveolar Bone Grafting/methods , Bone Transplantation/methodsABSTRACT
BACKGROUND: Peer-assisted learning (PAL) - where students take up a teaching role at an early stage of their training-is widely used in medical curricula. Many qualitative studies have investigated the perceptions and benefits of PAL, but no studies have longitudinally explored how peer teachers experienced their development. This could allow for a better understanding of PAL. In this study, we explored the perceived impact of being a peer teacher on the development of personal and professional competencies as a medical student. METHODS: We longitudinally conducted semi-structured interviews with peer teachers, during their 2-year teaching period in the skills lab at the University of Antwerp and applied descriptive thematic analysis. RESULTS: In total we gathered 47 interviews in 13 peer teachers (9 female, 4 male,. 1-7 interviews each). Peer teachers reported an increase in self-confidence, which gradually transformed into self-efficacy in clinical and teaching skills., Participants told us to be inspired by the previous generation of peer teachers. Their motivation shifted from personal benefits to benefiting others while becoming a role model themselves. The peer teachers illustrated how they developed maturity by integrating different CanMEDS roles. They grew in reflection, changed/transformed an initial mark-driven study drive into more patient-centered ambitions, and started developing a personal style. CONCLUSIONS: Our study suggests that being a peer teacher leads to more self-efficacy, in clinical and teaching skills, to become a role model with as motivation to benefit others and to grow towards a good doctor maturity. Although the task is to teach peers, this opportunity nurtures the practice and integration of various CanMEDS roles, not only that of scholar but also communicator, collaborator and leader, thereby positively influencing their personal and professional development and their identity as a doctor (professional role).
Subject(s)
Education, Medical, Undergraduate , Students, Medical , Humans , Male , Female , Curriculum , Peer Group , Qualitative Research , TeachingABSTRACT
Introduction: In challenging listening situations, speech perception with a cochlear implant (CI) remains demanding and requires high levels of listening effort, which can lead to increased levels of listening-related fatigue. The body of literature on these topics increases as the number of CI users rises. This scoping review aims to provide an overview of the existing literature on listening effort, fatigue, and listening-related fatigue among CI users and the measurement techniques to evaluate them. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements were used to conduct the scoping review. The search was performed on PubMed, Scopus, and Web of Science to identify all relevant studies. Results: In total, 24 studies were included and suggests that CI users experience higher levels of listening effort when compared to normal hearing controls using scales, questionnaires and electroencephalogram measurements. However, executing dual-task paradigms did not reveal any difference in listening effort between both groups. Uncertainty exists regarding the difference in listening effort between unilateral, bilateral, and bimodal CI users with bilateral hearing loss due to ambiguous results. Only five studies were eligible for the research on fatigue and listening-related fatigue. Additionally, studies using objective measurement methods were lacking. Discussion: This scoping review highlights the necessity for additional research on these topics. Moreover, there is a need for guidelines on how listening effort, fatigue, and listening-related fatigue should be measured to allow for study results that are comparable and support optimal rehabilitation strategies.
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Zebrafish are increasingly becoming an important model organism for studying the pathophysiological mechanisms of human diseases and investigating how these mechanisms can be effectively targeted using compounds that may open avenues to novel treatments for patients. The zebrafish skeleton has been particularly instrumental in modeling bone diseases as-contrary to other model organisms-the lower load on the skeleton of an aquatic animal enables mutants to survive to early adulthood. In this respect, the axial skeletons of zebrafish have been a good read-out for congenital spinal deformities such as scoliosis and degenerative disorders such as osteoporosis and osteoarthritis, in which aberrant mineralization in humans is reflected in the respective zebrafish models. Interestingly, there have been several reports of hereditary multisystemic diseases that do not affect the vertebral column in human patients, while the corresponding zebrafish models systematically show anomalies in mineralization and morphology of the spine as their leading or, in some cases, only phenotype. In this review, we describe such examples, highlighting the underlying mechanisms, the already-used or potential power of these models to help us understand and amend the mineralization process, and the outstanding questions on how and why this specific axial type of aberrant mineralization occurs in these disease models.
Subject(s)
Pharmaceutical Research , Scoliosis , Animals , Humans , Adult , Zebrafish/genetics , Spine , Zebrafish Proteins/geneticsABSTRACT
Previous studies revealed a link between inflammation and overactivation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in syndromes associated with aging. Pseudoxanthoma elasticum (PXE), a rare autosomal-recessive disorder, arises from mutations in ATP-binding cassette subfamily C member 6 (ABCC6). On a molecular level, PXE shares similarities with Hutchinson-Gilford progeria syndrome, such as increased activity of senescence-associated- beta-galactosidase or high expression of inflammatory factors. Thus, this study's aim was the evaluation of activated STAT3 and the influence of JAK1/2-inhibitor baricitinib (BA) on inflammatory processes such as the complement system in PXE. Analysis of activation of STAT3 was performed by immunofluorescence and Western blot, while inflammatory processes and complement system factors were determined based on mRNA expression and protein level. Our results assume overactivation of JAK/STAT3 signaling, increased expression levels of several complement factors and high C3 protein concentration in the sera of PXE patients. Supplementation with BA reduces JAK/STAT3 activation and partly reduces inflammation as well as the gene expression of complement factors belonging to the C1 complex and C3 convertase in PXE fibroblasts. Our results indicate a link between JAK/STAT3 signaling and complement activation contributing to the proinflammatory phenotype in PXE fibroblasts.
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BACKGROUND: No distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists. OBJECTIVE: To evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak. METHODS: We collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings. RESULTS: Our analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT. CONCLUSIONS: Findings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic.