ABSTRACT
BACKGROUND: Results of neurotological function diagnostics in the context of interdisciplinary vertigo assessment are usually formulated as free-text reports (FTR). These are often subject to high variability, which may lead to loss of information. The aim of the present study was to evaluate the completeness of structured reports (SR) and referrer satisfaction in the neurotological assessment of vertigo. MATERIALS AND METHODS: Neurotological function diagnostics performed as referrals (nâ¯= 88) were evaluated retrospectively. On the basis of the available raw data, SRs corresponding to FTRs from clinical routine were created by means of a specific SR template for neurotological function diagnostics. FTRs and SRs were evaluated for completeness and referring physician satisfaction (nâ¯= 8) using a visual analog scale (VAS) questionnaire. RESULTS: Compared to FTRs, SRs showed significantly increased overall completeness (73.7% vs. 51.7%, pâ¯< 0.001), especially in terms of patient history (92.5% vs. 66.7%, pâ¯< 0.001), description of previous findings (87.5% vs. 38%, pâ¯< 0.001), and neurotological (33.5% vs. 26.7%, pâ¯< 0.001) and audiometric function diagnostics (58% vs. 32.3%, pâ¯< 0.001). In addition, SR showed significantly increased referring physician satisfaction (VAS 8.8 vs. 4.9, pâ¯< 0.001). CONCLUSION: Neurotological SRs enable a significantly increased report completeness with higher referrer satisfaction in the context of interdisciplinary assessment of vertigo. Furthermore, SRs are particularly suitable for scientific data analysis, especially in the context of big data analyses.
ABSTRACT
Consumers can influence ecological patterns and processes through their trophic roles and contributions to the flow of energy through ecosystems. However, the diet and associated trophic roles of consumers commonly change during ontogeny. Despite the prevalence of ontogenetic variation in trophic roles of most animals, we lack an understanding of whether they change consistently across local populations and broad geographic gradients. We examined how the diet and trophic position of a generalist marine predator varied with ontogeny across seven broadly separated locations (~ 750 km). We observed a high degree of heterogeneity in prey consumed without evidence of spatial structuring in this variability. However, compound-specific isotope analysis of amino acids revealed remarkably consistent patterns of increasing trophic position through ontogeny across local populations, suggesting that the roles of this generalist predator scaled with its body size across space. Given the high degree of diet heterogeneity we observed, this finding suggests that even though the dietary patterns differed, the underlying food web architecture transcended variation in prey species across locations for this generalist consumer. Our research addresses a gap in empirical field work regarding the interplay between stage-structured populations and food webs, and suggests ontogenetic changes in trophic position can be consistent in generalist consumers.
Subject(s)
Ecosystem , Food Chain , Animals , Nutritional Status , Diet , Body SizeABSTRACT
BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.
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This article presents the case of a 33-year-old woman who consulted the authors' ENT clinic in the 39th week of pregnancy with recurrent epistaxis. A livid endonasal mass was found on the left side, subtotally displacing the nose and leading to deformation of the external nose. External biopsy provided no indications of malignancy. Postpartum CT of the paranasal sinuses revealed a mass destroying the cartilaginous nasal septum. Endoscopic resection of the finding was performed with preservation of the clinically sound nasal septal cartilage. Histopathological examination revealed a capillary hemangioma, which was classified as granuloma gravidarum due to its occurrence during pregnancy.
Subject(s)
Epistaxis , Hemangioma, Capillary , Nasal Cartilages , Nose Deformities, Acquired , Pregnancy Complications, Hematologic , Pregnancy Complications, Neoplastic , Humans , Female , Pregnancy , Adult , Epistaxis/diagnostic imaging , Epistaxis/pathology , Recurrence , Pregnancy Complications, Hematologic/diagnostic imaging , Pregnancy Complications, Hematologic/pathology , Biopsy , Nose Deformities, Acquired/diagnostic imaging , Nose Deformities, Acquired/pathology , Nasal Cartilages/diagnostic imaging , Nasal Cartilages/pathology , Hemangioma, Capillary/diagnostic imaging , Hemangioma, Capillary/pathology , Pregnancy Complications, Neoplastic/diagnostic imaging , Pregnancy Complications, Neoplastic/pathologyABSTRACT
This preliminary study investigates the differences between experimental periodontitis and peri-implantitis in a dog model, with a focus on the histopathology, inflammatory responses, and specific immunoregulatory activities driven by Th1/Th2-positive cells. Twelve dental implants were inserted into the edentulated posterior mandibles of 6 beagle dogs and were given 12 weeks for osseointegration. Experimental peri-implantitis and periodontitis (first mandible molar) were then induced using cotton-floss ligatures. Twelve weeks later, alveolar bones were quantitated by cone beam-computer tomography. Histopathologic analysis of the inflamed gingiva and periodontal tissues was performed by light microscopy, and the Th1/Th2 cell populations were investigated by flow cytometry. Peri-implantitis and periodontitis were both found to be associated with pronounced bone resorption effects, both to a similar degree vertically, but with a differential bone resorption pattern mesio-distally, and with a significantly higher and consistent bone resorption result in peri-implantitis, although with a higher variance of bone resorption in periodontitis. The histologic appearances of the inflammatory tissues were identical. The percentages of Th1/Th2 cells in the inflamed gingival tissues of both experimental peri-implantitis and periodontitis were also found to be similar. Experimental periodontitis and peri-implantitis in the dog model show essentially the same cellular pathology of inflammation. However, bone resorption was found to be significantly higher in peri-implantitis; the histopathologic changes in the periodontal tissues were similar in both groups but showed a higher interindividual variation in periodontitis and appeared more uniform in peri-implantitis. This preliminary study indicates that more focused experimental in vivo inflammation models need to be developed to better simulate the human pathology in the 2 different diseases and to have a valuable tool to investigate more specifically how novel treatments/prevention approaches may heal the differential adverse effects on bone tissue and on periodontium in periodontitis and in periimplantitis.
Subject(s)
Alveolar Bone Loss , Dental Implants , Peri-Implantitis , Periodontitis , Animals , Dental Implants/adverse effects , Dogs , OsseointegrationABSTRACT
BACKGROUND: Ultrasound diagnostics are widely used and are standard for radiologists, otolaryngologists, and oral and maxillofacial surgeons in the diagnostic work-up of various pathologies. There is agreement that digital documentation is urgently needed at present to improve and standardize the quality of sonographic documentation. There are more and more publications on the implementation of standardized documentation of findings in imaging diagnostics, including head and neck sonography. OBJECTIVE: The present work aims to determine the quality of routine head and neck sonography findings on a random basis, according to the criteria of the Bavarian Association of Statutory Health Insurance Physicians (KVB) at a selection of German university otolaryngology departments (ENT). MATERIALS AND METHODS: A total of 70 randomly selected anonymized written findings including image documentation from seven ENT departments were retrospectively analyzed by an experienced KVB examiner concerning fulfilment of KVB criteria. The data were evaluated descriptively. RESULTS: Of the 70 reports, 69 were eligible for evaluation. The average documentation completeness was 80.6%. A total of 9 findings were correctly documented in full (13%). The documentation completeness of the individual departments was sorted in ascending order from 68.1% to 93%. With 88.5% vs. 75%, the hospitals with a structured report showed a higher level of completeness. In 75% of the cases the hospitals with structured reports also had digital solutions for reporting and image archiving. CONCLUSION: In general, there is potential for optimization regarding the completeness and quality of routinely prepared head and neck sonography findings at the selected university ENT departments. The implementation of structured reporting masks and the conversion of analogue documentation into digital solutions as well as digital networking with the hospital information systems, picture archiving and communication systems should be promoted. Supervision by senior doctors is required to ensure the quality of findings of inexperienced colleagues and to help to achieve standards in reporting.
Subject(s)
Head , Neck , Documentation , Head/diagnostic imaging , Hospitals, University , Humans , Neck/diagnostic imaging , Retrospective Studies , UltrasonographyABSTRACT
The Third Modeling Workshop focusing on bioprocess modeling was held in Kenilworth, NJ in May 2019. A summary of these Workshop proceedings is captured in this manuscript. Modeling is an active area of research within the biotechnology community, and there is a critical need to assess the current state and opportunities for continued investment to realize the full potential of models, including resource and time savings. Beyond individual presentations and topics of novel interest, a substantial portion of the Workshop was devoted toward group discussions of current states and future directions in modeling fields. All scales of modeling, from biophysical models at the molecular level and up through large scale facility and plant modeling, were considered in these discussions and are summarized in the manuscript. Model life cycle management from model development to implementation and sustainment are also considered for different stages of clinical development and commercial production. The manuscript provides a comprehensive overview of bioprocess modeling while suggesting an ideal future state with standardized approaches aligned across the industry.
Subject(s)
Biotechnology , Computer Simulation , Models, TheoreticalABSTRACT
Implantation of allograft tissues has massively grown over the last years, especially in the fields related to sports medicine. Beside the fact that often no autograft option exists, autograft related disadvantages as donor-site morbidity and prolonged operative time are drastically reduced with allograft tissues. Despite the well documented clinical success for bone allograft procedures, advances in tissue engineering raised the interest in meniscus, osteochondral and ligament/tendon allografts. Notably, their overall success rates are constantly higher than 80%, making them a valuable treatment option in orthopaedics, especially in knee surgery. Complications reported for allografting procedures are a small risk of disease transmission, immunologic rejection, and decreased biologic incorporation together with nonunion at the graft-host juncture and, rarely, massive allograft resorption. Although allografting is a successful procedure, improved techniques and biological knowledge to limit these pitfalls and maximize graft incorporation are needed. A basic understanding of the biologic processes that affect the donor-host interactions and eventual incorporation and remodelling of various allograft tissues is a fundamental prerequisite for their successful clinical use. Further, the importance of the interaction of immunologic factors with the biologic processes involved in allograft incorporation has yet to be fully dissected. Finally, new tissue engineering techniques and use of adjunctive growth factors, cell based and focused gene therapies may improve the quality and uniformity of clinical outcomes. The aim of this review is to shed light on the biology of meniscus, osteochondral and ligament/tendon allograft incorporation and how collection and storage techniques may affect graft stability and embodiment.Level of evidence V.
Subject(s)
Allografts/physiology , Knee Joint/surgery , Allografts/immunology , Bone Transplantation , Cartilage/cytology , Cartilage/transplantation , Chondrocytes/transplantation , Cytokines/metabolism , Humans , Knee Joint/metabolism , Matrix Metalloproteinases/metabolism , Meniscus/transplantation , Regeneration , Tendons/transplantation , Transplantation, HomologousABSTRACT
This article presents the case of a 39-year-old woman receiving injection therapy for cervicalgia. Due to accidental injection into the cervical spinal cord, the patient suffered from syncope, sensomotoric deficit, and bilateral neural hearing loss. Injection therapies for spinal disorders are routinely carried out in clinical practice, despite a low level of evidence and potentially severe complications. In the event of neuro-otologic complications, prompt evaluation by an otologist should be sought and rehabilitation initiated if necessary.
Subject(s)
Hearing Loss, Sudden , Neck Pain , Adult , Female , Hearing Loss, Bilateral , Hearing Loss, Sudden/etiology , Humans , Injections/adverse effects , Neck Pain/therapyABSTRACT
BACKGROUND: Persistent dizziness symptoms after cochlear implantation have an impact on quality of life. In this study, the effects of bilateral cochlear implants (CI) on quality of life as well as on subjective dizziness complaints are analyzed using questionnaires, some of which have never been applied before in these patient collectives. OBJECTIVE: In this article, questionnaires for the assessment of dizziness symptoms and quality of life are introduced in order to realize quality assurance. MATERIALS AND METHODS: A total of 32 patients with bilateral CI were questioned regarding dizziness symptoms and quality of life. The Nijmegen Cochlear Implant Questionnaire (NCIQ) was used. In the case of reported regular dizziness, the Vertigo Handicap Questionnaire (VHQ) and the Vertigo Symptom Scale (VSS) were also assessed. RESULTS: Persistent dizziness symptoms were shown in 8 of 32 patients. Quality of life was measured with the NCIQ and was improved significantly (p < 0.001) by 23.7% after the second CI. The dizziness symptoms changed slightly (VHQ -11.2%; VSS +16.4%) after the second implantation. CONCLUSION: The results show that the questionnaires are valid instruments for documenting quality of life and dizziness symptoms for quality assurance. These questionnaires may be applied as a complement or an alternative to device-based measurements of peripheral vestibular dysfunction.
Subject(s)
Cochlear Implantation , Dizziness , Vertigo , Cochlear Implantation/adverse effects , Dizziness/etiology , Humans , Quality of Life , Surveys and QuestionnairesABSTRACT
Osteoarthritis (OA) is a degenerative joint condition characterized by painful cartilage lesions that impair joint mobility. Current treatments such as lavage, microfracture, and osteochondral implantation fail to integrate newly formed tissue with host tissues and establish a stable transition to subchondral bone. Similarly, tissue-engineered grafts that facilitate cartilage and bone regeneration are challenged by how to integrate the graft seamlessly with surrounding host cartilage and/or bone. This review centers on current approaches to promote cartilage graft integration. It begins with an overview of articular cartilage structure and function, as well as degenerative changes to this relationship attributed to aging, disease, and trauma. A discussion of the current progress in integrative cartilage repair follows, focusing on graft or scaffold design strategies targeting cartilage-cartilage and/or cartilage-bone integration. It is emphasized that integrative repair is required to ensure long-term success of the cartilage graft and preserve the integrity of the newly engineered articular cartilage. Studies involving the use of enzymes, choice of cell source, biomaterial selection, growth factor incorporation, and stratified versus gradient scaffolds are therefore highlighted. Moreover, models that accurately evaluate the ability of cartilage grafts to enhance tissue integrity and prevent ectopic calcification are also discussed. A summary and future directions section concludes the review.
Subject(s)
Cartilage, Articular , Osteoarthritis , Tissue Engineering , Aging/metabolism , Aging/pathology , Animals , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Cartilage, Articular/surgery , Humans , Osteoarthritis/metabolism , Osteoarthritis/pathology , Osteoarthritis/surgery , Wounds and Injuries/metabolism , Wounds and Injuries/pathology , Wounds and Injuries/surgeryABSTRACT
Absorbed collagen sponge (ACS)/bone morphogenetic protein-2 (BMP-2) are widely used in clinical practise for bone regeneration. However, the application of this product was found to be associated with a significant pro-inflammatory response, particularly in the early phase after implantation. This study aimed to clarify if the pro-inflammatory activities, associated with BMP-2 added to ACS, were related to the physical state of the carrier itself, i.e., a wet or a highly dehydrated state of the ACS, to the local degree of vascularisation and/or to local biomechanical factors. ACS (0.8 cm diameter)/BMP-2 were implanted subcutaneously in the back of 12 eight-week-old Sprague Dawley rats. Two days after surgery, the implanted materials were retrieved and analysed histologically and histomorphometrically. The acute inflammatory response following implantation of ACS was dependent of neither the presence or absence of BMP-2 nor the degree of vascularization in the surrounding tissue nor the hydration state (wet versus dry) of the ACS material at the time of implantation. Differential micro biomechanical factors operating at the implantation site appeared to have an influence on the thickness of inflammation. We conclude that the degree of the early inflammatory response of the ACS/BMP-2 may be associated with the physical and chemical properties of the carrier material itself.
Subject(s)
Absorbable Implants/adverse effects , Bone Morphogenetic Protein 2/metabolism , Collagen/metabolism , Inflammation/etiology , Inflammation/metabolism , Animals , Bone Regeneration , Inflammation/pathology , Macrophages/immunology , Macrophages/metabolism , Macrophages/pathology , Male , Neovascularization, Physiologic , Osteogenesis , Rats , Recombinant ProteinsABSTRACT
Plasmonic nanorings provide the unique advantage of a pronounced plasmonic field enhancement inside their core. If filled with a polarizable medium, it may significantly enhance its optical effects. Here, we demonstrate this proposition by filling gold nanorings with lithium niobate. The generated second harmonic signal is compared to the signal originating from an unpatterned lithium niobate surface. Measurements and simulation confirm an enhancement of about 20. Applications requiring nanoscopic localized light sources like fluorescence spectroscopy or quantum communication will benefit from our findings.
ABSTRACT
BACKGROUND: The audiological treatment of children with aural atresia makes high demands on physicians and acousticians. Conventional hearing systems are often not tolerated by children and therefore do not meet the needs of the early and efficient therapy of hearing disorders. Aim of the present study was the evaluation of the audiological functional gain in children with uni- and bilateral aural atresia provided with the middle ear implant Vibrant Soundbridge(®) (VSB(®)) below the age of 6 years as well as the analysis of parents' satisfaction assessed with questionnaires. MATERIAL AND METHODS: The VSB(®) was implanted in 16 children, 13 with unilateral and 3 with bilateral aural atresia, with the mean age of 2;11±1;6 years. 3 months after the first fitting of the audio processor, pure-tone audiometry via free field testing with and without the hearing system was performed. Furthermore, parents completed a standardized questionnaire to evaluate their satisfaction with the VSB(®) treatment quality. The questionnaire included items on the acceptance by children, handling, listening effort, behavior, satisfaction, quality of life, aesthetics, and the length of daily use. RESULTS: The use of the VSB(®) resulted in a significantly improved hearing level: 20 dB on average (Z=- 3.06; p=0.002; n=12). The analysis of parents' questionnaire demonstrated high or very high satisfaction with VSB(®) in all subjects. Primarily, the length of daily use of the VSB(®) was significantly higher than that of the hearing system used before with 10.0±2.1 vs. 2.7±2.2 h per day (Z=- 3.06; p=0.002; n=14). CONCLUSION: The VSB(®) presented a good alternative for audiological treatment of uni- and bilateral aural atresia at toddler and pre-school age.
Subject(s)
Hearing Loss, Conductive , Ossicular Prosthesis , Quality of Life , Audiometry, Pure-Tone , Child, Preschool , Ear , Hearing Aids , Humans , Infant , Treatment OutcomeABSTRACT
BACKGROUND/OBJECTIVES: The metabolic equivalent (MET) is a construct that is commonly used to quantify physical activity as well as exercise performance. 'One MET' is equal to a resting oxygen uptake of 3.5 ml O2 kg(-1) min(-)(1). However, this assumption is unlikely valid in obese subjects. The aim of our study was to quantify the difference between calculated and measured METs in overweight to severely obese subjects and to provide body mass index (BMI)-specific MET correction factors. SUBJECTS/METHODS: Resting oxygen uptake (VO2-REE) was measured in 1331 patients with a BMI >25 kg m(-2) (72.0% women; age: 42.5 ± 13.0 years; BMI: 42.5 ± 7.0 kg m(-)(2)) by indirect calorimetry and MET-REE, that is, VO2-REE related to body weight was calculated. Six hundred and fifty-two subjects (70.9% women) additionally underwent a bicycle cardiopulmonary exercise test for measurement of maximal MET (MET peak). RESULTS: Mean MET-REE was 2.47 ± 0.33 ml O2 kg(-1) min(-1) in women and 2.62 ± 0.34 ml O2 kg(-1) min(-1) in men, that is, markedly lower than the expected 3.5 ml O2 kg(-1) min(-1). MET-REE decreased with increasing BMI (P<0.001 for both sexes). On this dataset, gender-specific MET correction factors were developed for distinct BMI groups. During the exercise test, women performed 4.4 ± 1.3 MET peak and men 4.7 ± 1.3. After applying our correction factors, MET peak increased to 6.2 ± 1.7 and 6.1 ± 1.6, respectively. CONCLUSIONS: Data indicate that the commonly used 1-MET value of 3.5 ml O2 kg(-)(1) min(-)(1) largely overestimates values in overweight to severely obese subjects. Our correction factors can help to reduce this systematic error and thus appear to be valuable for clinical practice as well as research studies.
Subject(s)
Energy Metabolism , Exercise Tolerance , Metabolic Equivalent , Obesity/diagnosis , Oxygen Consumption , Adolescent , Adult , Aged , Body Fat Distribution , Body Mass Index , Calorimetry, Indirect , Cross-Sectional Studies , Exercise Test , Female , Humans , Male , Middle Aged , Obesity/metabolism , Obesity/physiopathology , Physical Fitness , Practice Guidelines as Topic , Rest , Retrospective Studies , Sex Factors , Switzerland/epidemiologyABSTRACT
OBJECTIVE: Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment. DESIGN: Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment. RESULTS: As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women. CONCLUSION: Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.
Subject(s)
Cerebellum/physiopathology , Feeding Behavior , Gastric Bypass , Hypothalamus/physiopathology , Magnetic Resonance Imaging , Obesity, Morbid/surgery , Weight Loss , Adult , Case-Control Studies , Cerebellum/pathology , Cross-Sectional Studies , Cues , Female , Food Preferences , Humans , Hunger , Hypothalamus/pathology , Obesity, Morbid/complications , Obesity, Morbid/physiopathology , Photic Stimulation , Satiation , Surveys and Questionnaires , Treatment OutcomeABSTRACT
The onset and timing of the growth of children and adolescents occurs with considerable variability in cohorts of the same chronological age. The musculoskeletal system changes in proportion over time, and lever-arm changes, altered individual flexibility, and strength lead to age-specific injury patterns in youth sports. In sports, juniors are commonly grouped according to their chronological age. Early- and late-maturing children and adolescents might therefore not routinely be trained in relation to their biology. This not only represents a risk for overuse and injury but might limit their development in sports. To obtain information about the biological age of children is challenging. Numerous methods have been studied and validated. However, the implementation of these methods on a large scale is still to come. This report provides a brief overview of growth dynamics in relation to youth sports injuries and describes a few challenges for the future.
Subject(s)
Athletic Injuries/physiopathology , Child Development , Cumulative Trauma Disorders/physiopathology , Adolescent , Athletic Injuries/prevention & control , Bone Density/physiology , Cartilage/physiology , Child , Cumulative Trauma Disorders/prevention & control , Humans , Physical Education and Training , Risk FactorsABSTRACT
The efficacy of biological therapeutics against cartilage degradation in osteoarthritis is restricted by the limited transport of macromolecules through the dense, avascular extracellular matrix. The availability of biologics to cell surface and matrix targets is limited by steric hindrance of the matrix, and the microstructure of matrix itself can be dramatically altered by joint injury and the subsequent inflammatory response. We studied the transport into cartilage of a 48 kDa anti-IL-6 antigen binding fragment (Fab) using an in vitro model of joint injury to quantify the transport of Fab fragments into normal and mechanically injured cartilage. The anti-IL-6 Fab was able to diffuse throughout the depth of the tissue, suggesting that Fab fragments can have the desired property of achieving local delivery to targets within cartilage, unlike full-sized antibodies which are too large to penetrate beyond the cartilage surface. Uptake of the anti-IL-6 Fab was significantly increased following mechanical injury, and an additional increase in uptake was observed in response to combined treatment with TNFα and mechanical injury, a model used to mimic the inflammatory response following joint injury. These results suggest that joint trauma leading to cartilage degradation can further alter the transport of such therapeutics and similar-sized macromolecules.
Subject(s)
Cartilage, Articular/injuries , Cartilage, Articular/metabolism , Immunoglobulin Fab Fragments/immunology , Immunoglobulin Fab Fragments/metabolism , Interleukin-6/immunology , Adult , Animals , Cartilage, Articular/immunology , Cattle , Female , Humans , Immunoglobulin Fab Fragments/therapeutic use , Protein Transport , Stress, Mechanical , Tumor Necrosis Factor-alpha/therapeutic useABSTRACT
In the Atlantic region of Canada, there are close to 50 land-based freshwater aquaculture facilities, most of which discharge wastewater to freshwater receiving environments. This study was designed to assess the chemical and toxicological characteristics of sediments in those receiving environments. Thirty sediment samples were collected from 3 locations (upstream, outfall and downstream) at seven freshwater aquaculture facilities. Toxicity tests conducted included amphipod growth, amphipod survival and Microtox™. Sediments were also analysed for ammonia/porewater ammonia, redox and sulphide. Porewater ammonia concentration for the amphipod survival test ranged from 0.01 to 42 mg/L at the conclusion of the 14-day survival test. Ammonia concentration in sediment ranged from 0.3-202 µg/g, sulphide concentration ranged from 0.15 to 17.4 µg/g, yet redox ranged from 32 to 594 mV. Microtox™ IC50 values ranged from 108,00 to >164,000 mg/L, yet amphipod survival ranged from 0 to 100%, depending on sampling locations. Amphipod survival was significantly related (P < 0.05) to porewater ammonia (at time = 0 and 14 days) and Microtox™ IC50 was significantly related (P < 0.05) to ammonia, sulphide and redox levels. These results indicate that discharges from some the land-based aquaculture facilities are impacting sediment dwelling benthic invertebrates at the outfall but that impact largely disappears by 100 m downstream. Furthermore those impacts were rarely detected during the early winter season, when biomass production was at the lowest.