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Background: Loosening of the glenoid component continues to be the foremost cause of medium and long-term failure of shoulder replacements. The purpose of this study was to evaluate the clinical and radiographic results of a minimally cemented all-polyethylene pegged glenoid component designed for biologic fixation.Methods: Forty-four shoulders in forty-one patients with a mean age of sixty-six years underwent total shoulder arthroplasty with a pegged bone-ingrowth glenoid component. Outcome data included the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and visual analog scales. A detailed radiographic analysis was performed by two board-certified musculoskeletal radiologists who were blinded to clinical and patient-reported outcomes. The radiographs were evaluated with regard to the presence of radiolucent lines at the bone-cement interface, implant seating, and the radiodensity between the flanges of the central peg.Results: The mean duration of clinical follow-up was four years and the mean duration of radiographic follow-up was three years. Twenty shoulders had perfect seating and radiolucency grades, thirty had increased radiodensity between the flanges of the central peg, and three demonstrated osteolysis. Radiodensity about the uncemented central peg at the time of the latest follow-up was positively associated with perfect seating and radiolucency grades on the initial postoperative radiographs (p = 0.03, Fisher exact test). The Simple Shoulder Test score, the American Shoulder and Elbow Surgeons score, and all visual analog scale scores had improved significantly (p < 0.01) at the time of the latest follow-up.Conclusions: Total shoulder arthroplasty with a minimally cemented, all-polyethylene, pegged glenoid implant can yield stable and durable fixation at short to medium-term follow-up (mean, four years). [ABSTRACT FROM AUTHOR]

The majority of cases of glenohumeral arthritis in older adults are primary osteoarthritis and treatment algorithms are well defined, with shoulder arthroplasty providing reliable pain relief and functional improvement of satisfactorily duration. In younger adults, however, diagnoses are more complex and arthroplasty outcomes are less durable. Arthroscopy may be useful both as a diagnostic tool for characterizing lesions and as a therapeutic tool for debridement. Arthroscopic debridement is most likely to benefit patients with mild glenohumeral arthritis, small lesions, and involvement of only one side of the glenohumeral joint. Reconstruction of the humeral joint surface may consist of cartilage repair or reconstruction, resurfacing arthroplasty, or arthroplasty with a stemmed component. Patients treated with hemiarthroplasty avoid glenoid implant loosening, but the procedure provides less predictable pain relief than does total shoulder arthroplasty and may lead to increased postoperative glenoid erosion. [ABSTRACT FROM AUTHOR]

Background: Glenohumeral hemiarthroplasty is well established as a method to treat glenohumeral arthritis. This study was designed to report longer-term results and to provide a decision model to assist surgeons in achieving successful outcomes. Our selection strategy for hemiarthroplasty included shoulders with (1) a concentric glenoid with eburnated bone, (2) a nonconcentric glenoid that could be converted to a smooth concentric surface, and (3) a humeral head centered within the glenoid after soft-tissue balancing.Methods: Fifty-seven consecutive patients (sixty-four shoulders) who had osteoarthritis of the glenohumeral joint, without advanced disease in the glenoid, were treated with hemiarthroplasty. In each instance, a modular prosthesis was implanted. Clinical assessment was performed preoperatively and at one-year intervals postoperatively for at least five years with use of patient self-assessment instruments, including the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and a visual analog pain scale. A detailed radiographic analysis was performed to determine the presence of glenohumeral subluxation, periprosthetic radiolucency, and glenoid bone loss.Results: Forty-three patients (fifty shoulders) were followed for a minimum of five years (mean, 7.5 years). Of the remaining fourteen patients (fourteen shoulders), ten were lost to follow-up, three had died, and one was excluded. For the Simple Shoulder Test, and for every visual analog scale measure, the results at the final follow-up evaluation were significantly better than the preoperative results (p < 0.0001 for each). The mean Simple Shoulder Test score at the time of the final follow-up was 9.4 positive responses compared with 9.7 positive responses at the two-year evaluation (p = 0.32), and the mean visual analog scale score for pain was 18.6 points compared with 14.9 points at two years (p = 0.45). Radiographic analysis showed the majority of stems had either no lucency or lucencies only near the tip of the stem. Glenoid bone loss and subluxation improved postoperatively, and the results were maintained at the final follow-up evaluation.Conclusions: Shoulder hemiarthroplasty provides sustained good-to-excellent pain relief and functional improvement at five to ten years postoperatively in carefully selected patients with osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Compaction bone-grafting has been suggested as a means of improving the stability of the humeral component in shoulder arthroplasty, but the clinical and radiographic results of the procedure have not been reported in the literature, to our knowledge. To address this deficit, we report on a series of shoulder arthroplasties performed with compaction bone-grafting to secure humeral component fixation. These prostheses were implanted in shoulders demonstrating a suboptimal interference fit of the humeral component.Methods: Fifty-eight shoulders in fifty-three patients were treated with prosthetic shoulder arthroplasty that included compaction bone-grafting. Clinical assessments were performed at regular intervals with use of visual analog scales for pain, shoulder comfort and function, and overall quality of life, and with use of patient self-assessments including the American Shoulder and Elbow Surgeons Score and the validated Simple Shoulder Test. A detailed radiographic analysis was performed by three raters to determine whether radiolucent lines were present immediately postoperatively and at a later follow-up interval. The humeral tilt angle was determined by measuring the angle between the humeral axis and the component. Subsidence was also evaluated. The mean of the raters' measurements was used in the analysis.Results: The mean duration of follow-up was sixty-nine months (range, twenty-six to 148 months). No loose stems were observed, and no humeral component was revised. At the time of follow-up, there was significant improvement in the Simple Shoulder Test scores and all visual analog scores (p < 0.0001 in each instance). Thirty-four stems had no radiolucent line at the time of follow-up, and the mean maximum thickness of the lucent lines was 0.21 mm in the entire group of fifty-eight shoulders. Most lucent lines occurred near the distal stem tip. The mean tilt of the valgus and varus humeral components was 2.2 degrees and 2.6 degrees , respectively, on the immediate postoperative radiographs. No humeral component shifted from varus to valgus or vice versa. The duration of follow-up was not correlated with the maximum thickness of the humeral component lucency, and the presence or absence of a prosthetic glenoid was also unrelated to the maximum thickness of the lucency.Conclusions: Compaction bone-grafting in shoulder arthroplasty can yield stable and durable fixation of the humeral component, as seen clinically and radiographically, without use of cement. Our findings provide evidence that compaction bone-grafting in shoulder arthroplasty is an option to ensure intermediate-term fixation (at a mean of five years) of humeral components that have a suboptimal fit. [ABSTRACT FROM AUTHOR]

Background: Glenohumeral hemiarthroplasty is well established as a method to treat glenohumeral arthritis. This study was designed to report longer-term results and to provide a decision model to assist surgeons in achieving successful outcomes. Our selection strategy for hemiarthroplasty included shoulders with (1) a concentric glenoid with eburnated bone, (2) a nonconcentric glenoid that could be converted to a smooth concentric surface, and (3) a humeral head centered within the glenoid after soft-tissue balancing.Methods: Fifty-seven consecutive patients (sixty-four shoulders) who had osteoarthritis of the glenohumeral joint, without advanced disease in the glenoid, were treated with hemiarthroplasty. In each instance, a modular prosthesis was implanted. Clinical assessment was performed preoperatively and at one-year intervals postoperatively for at least five years with use of patient self-assessment instruments, including the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and a visual analog pain scale. A detailed radiographic analysis was performed to determine the presence of glenohumeral subluxation, periprosthetic radiolucency, and glenoid bone loss.Results: Forty-three patients (fifty shoulders) were followed for a minimum of five years (mean, 7.5 years). Of the remaining fourteen patients (fourteen shoulders), ten were lost to follow-up, three had died, and one was excluded. For the Simple Shoulder Test, and for every visual analog scale measure, the results at the final follow-up evaluation were significantly better than the preoperative results (p < 0.0001 for each). The mean Simple Shoulder Test score at the time of the final follow-up was 9.4 positive responses compared with 9.7 positive responses at the two-year evaluation (p = 0.32), and the mean visual analog scale score for pain was 18.6 points compared with 14.9 points at two years (p = 0.45). Radiographic analysis showed the majority of stems had either no lucency or lucencies only near the tip of the stem. Glenoid bone loss and subluxation improved postoperatively, and the results were maintained at the final follow-up evaluation.Conclusions: Shoulder hemiarthroplasty provides sustained good-to-excellent pain relief and functional improvement at five to ten years postoperatively in carefully selected patients with osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Prosthetic replacement of the glenohumeral joint can relieve pain and improve shoulder function for patients with end-stage inflammatory arthritis. The purpose of this study was to prospectively analyze the clinical, functional, and radiographic outcomes of shoulder reconstruction with hemiarthroplasty or total shoulder arthroplasty.Methods: In this multicenter prospective study, clinical history, physical examination, and self-assessment tools including a visual analogue scale, the Simple Shoulder Test, and an activities questionnaire were used to measure comfort, quality of life, and function. Radiographic outcome was determined by assessing the severity of the disease, the adaptation of the prosthesis to the anatomy, the implant position and relationships, and the restoration of glenohumeral alignment.Results: At the time of follow-up, at a minimum of twenty-four months (mean, thirty-nine months), the thirty-six shoulders treated with a hemiarthroplasty and the twenty-five treated with a total shoulder arthroplasty showed significant improvement (p < 0.0001) as demonstrated by the visual analogue scale and the Simple Shoulder Test as well as improvements in the components of the activities questionnaire. Active forward elevation was significantly better (p < 0.004) after the total shoulder arthroplasties than after the hemiarthroplasties. The presence of extremely severe disease did not affect the clinical outcome. Prosthetic adaptation to the anatomy and restoration of glenohumeral alignment resulted in significant improvement in certain motion parameters and were associated with one another (p < 0.001). Restoration of glenohumeral alignment resulted in significant improvements in overall quality of life (p = 0.038), use of the arm for work and play (p = 0.014), and range of motion (p = 0.0004) compared with those parameters when alignment had not been restored. Glenoid erosion occurred in four of the shoulders treated with hemiarthroplasty. Two of the glenoid components used in the total shoulder arthroplasties loosened.Conclusions: Patients with inflammatory arthritis treated with hemiarthroplasty or total shoulder arthroplasty can be expected to have improved comfort, range of motion, and function. Restoration of glenohumeral alignment appears to lead to even greater improvement in these clinical parameters. [ABSTRACT FROM AUTHOR]

Current indications for shoulder arthrodesis include posttraumatic brachial plexus injuries, paralysis of the deltoid muscle and rotator cuff, chronic infection, failed revision arthroplasty, severe refractory instability, and bone deficiency following resection of a tumor in the proximal aspect of the humerus. The trapezius, levator scapulae, serratus anterior, and rhomboid muscles must be functional to optimize the functional result following shoulder arthrodesis. A consensus has not been reached concerning the ideal position of the shoulder arthrodesis, although excessive abduction or flexion has been associated with chronic postoperative pain. Decortication of both the acromiohumeral and the glenohumeral surfaces to increase the surface area available for arthrodesis is the most common means for obtaining successful fusion. Although there are numerous methods for stabilization of a shoulder arthrodesis, the most popular method today is probably the AO technique with either a single plate or double plates. [ABSTRACT FROM AUTHOR]

Installed onboard the German research aircraft HALO, the integrated-path differential-absorption (IPDA) lidar CHARM-F measures weighted vertical columns of both greenhouse gases (GHG) below the aircraft and along its flight track, aiming at high accuracy and precision. Results will be shown from the deployment during the CoMet field campaign that was carried out in spring 2018, with its main focus on one of the major European hot spots in methane emissions: the Upper Silesian Coal Basin (USCB) in Poland. First analyses reveal a measurement precision of below 0.5% for 20-km averages and also low bias, which was assessed by comparison with in-situ instruments. The measurements flights were designed to capture individual CH4 and CO2 plumes from e.g. coal mine venting and coal-fired power plants, respectively, but also to measure large and regional scale GHG gradients and to provide comparisons with the Total Carbon Column Observing Network (TCCON). Many other different instruments, both airborne and ground-based, complemented the lidar measurements to provide a comprehensive dataset for model analyses. CHARM-F also acts as the airborne demonstrator for MERLIN, the “Methane Remote Lidar Mission”, conducted by the German and French space agencies, DLR and CNES, with launch foreseen in ~ 2024. In this context, the airborne lidar data are likewise important for mission support such as for e.g. algorithm development and improvement and, moreover, the CoMet mission was also an important step for MERLIN validation preparation.

Particle attenuated backscatter and depolarization ratio at 532 nm from the WALES (Water Vapor Lidar Experiment in Space) instrument are used in combination with the radar reflectivity from the 35 GHz MIRA35 cloud radar in order to perform an aerosol-cloud target classification on the lidar/radar collocated observations carried out with the High Altitude and LOng-range research aircraft (HALO), in high temporal and spatial resolution. The methodology is applied to the measurements conducted during the North Atlantic Waveguide and Downstream Impact Experiment (NAWDEX) in fall 2016. Here, we present one case study to show the feasibility and information context of the aerosol-cloud discrimination, which can serve as a good complement to the Cloud target categorization applied already in the measurements. Our results demonstrate that the developed mask is capable to identify complex stratifications with different aerosol and cloud types and even aerosol layers of low signal.

In 2015, the new airborne lidar CHARM-F for the measurement of the greenhouse gases carbon dioxide and methane was set into operation. It is an integrated path differential absorption (IPDA) lidar designed for the use onboard the German research aircraft HALO. Due to its high technological similarity to the MERLIN space lidar, it is also a demonstrator for the space system. Here, we report on CHARM-F’s technology, the experiences with the IPDA lidar method and the achieved performance.

Airborne lidar backscatter data is used to determine in- and out-of-cloud regions. Lidar measurements of water vapor together with model temperature fields are used to calculate relative humidity over ice (RHi). Based on temperature and RHi we identify different stages of cirrus evolution: homogeneous and heterogeneous freezing, depositional growth, ice sublimation and sedimentation. We will present our classification scheme and first applications on mid-latitude cirrus clouds.

The CNES/DLR MERLIN satellite mission aims at measuring methane dry-air mixing ratio column (XCH4) and thus improving surface flux estimates. In order to get a 1% precision on XCH4 measurements, MERLIN signal processing assumes an averaging of data over 50 km. The induced biases due to the non-linear IPDA lidar equation are not compliant with accuracy requirements. This paper analyzes averaging biases issues and suggests correction algorithms tested on realistic simulated scenes.

The stringent requirements for both the frequency stability and power reference represent a challenging task for Integrated Path Differential Absorption Lidars (IPDA) to measure greenhouse gas columns from satellite or aircraft. Currently, the German-French methane mission MERLIN (Methan Remote Lidar Mission) is prepared. At the same time CHARM-F, an aircraft installed system has been developed at DLR as an airborne demonstrator for a spaceborne greenhouse gas mission. The concepts and realization of these important sub-systems are discussed.

Aerosol and water vapor measurements were performed with the lidar system WALES of the German Aerospace Center (DLR) onboard the German research aircraft G550-HALO during the HALO Techno-Mission in October and November 2010 and during the ML-Cirrus mission in March and April 2014 over Central Europe and the North Atlantic region. Curtains composed of lidar profiles beneath the aircraft show the water vapor mixing ratio and the backscatter ratio. Temperature data from ECMWF model analysis are used to calculate the relative humidity above ice (RHi) in the 2-D field along the flight track to study the RHi distribution inside and outside of cirrus clouds at different stages of cloud evolution.

An important aeronautics application of lidar is the airborne remote detection of Clear Air Turbulence which cannot be performed with onboard radar. We report on a DLR-developed lidar system for the remote detection of such turbulent areas in the flight path of an aircraft. The lidar, consisting of a high-power UV laser transmitter and a direct detection system, was installed on a Dutch research aircraft. Flight tests executed in 2013 demonstrated the performance of the lidar system to detect local subtle variations in the molecular backscatter coefficient indicating the turbulence some 10 to 15 km ahead.

Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM®) to BCG in patients after transurethral resection (TURB) of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001). Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1) as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1) strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1) virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK), a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD) located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

Abstract Background Previous studies have revealed a wide-spread occurence of the partial and complete genomes of the reverse-transcribing pararetroviruses in the nuclear genomes of herbaceous plants. Although the absence of the virus-encoded integrases attests to the random and incidental incorporation of the viral sequences, their presence could have functional implications for the virus-host interactions. Hypothesis Analyses of two nuclear genomes of grapevine revealed multiple events of horizontal gene transfer from pararetroviruses. The ~200–800 bp inserts that corresponded to partial ORFs encoding reverse transcriptase apparently derived from unknown or extinct caulimoviruses and tungroviruses, were found in 11 grapevine chromosomes. In contrast to the previous reports, no reliable cases of the inserts derived from the positive-strand RNA viruses were found. Because grapevine is known to be infected by the diverse positive-strand RNA viruses, but not pararetroviruses, we hypothesize that pararetroviral inserts have conferred host resistance to these viruses. Furthermore, we propose that such resistance involves RNA interference-related mechanisms acting via small RNA-mediated methylation of pararetroviral DNAs and/or via degradation of the viral mRNAs. Conclusion The pararetroviral sequences in plant genomes may be maintained due to the benefits of virus resistance to this class of viruses conferred by their presence. Such resistance could be particularly significant for the woody plants that must withstand years- to centuries-long virus assault. Experimental research into the RNA interference pathways involving the integrated pararetroviral inserts is required to test this hypothesis. Reviewers This article was reviewed by Arcady R. Mushegian, I. King Jordan, and Eugene V. Koonin.

Abstract Background Bovine viral diarrhea virus (BVDV) is the prototype representative of the pestivirus genus in the Flaviviridae family. It has been shown that the initiation of translation of BVDV RNA occurs by an internal ribosome entry mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and 3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A putative pseudoknot structure has been recognized in the BVDV 5'UTR in close proximity to the AUG start codon. A pseudoknot structure is characteristic for flavivirus IRESes and in the case of the closely related classical swine fever virus (CSFV) and the more distantly related Hepatitis C virus (HCV) pseudoknot function in translation has been demonstrated. Results To characterize the BVDV IRESes in detail, we studied the BVDV translational initiation by transfection of dicistronic expression plasmids into mammalian cells. A region coding for the amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient initiation of translation. The translation efficiency mediated by the IRES of BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed translation in BHK cells. Compared to the poliovirus IRES increased expression levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while lower levels are observed in human cell lines. Site directed mutagenesis revealed that a RNA pseudoknot upstream of the initiator AUG is an important structural element for IRES function. Mutants with impaired ability to base pair in stem I or II lost their translational activity. In mutants with repaired base pairing either in stem 1 or in stem 2 full translational activity was restored. Thus, the BVDV IRES translation is dependent on the pseudoknot integrity. These features of the pestivirus IRES are reminiscent of those of the classical swine fever virus, a pestivirus, and the hepatitis C viruses, another genus of the Flaviviridae. Conclusion The IRES of the non-cytopathic BVDV SD-1 strain displays features known from other pestivirus IRESes. The predicted pseudoknot in the 5'UTR of BVDV SD-1 virus represents an important structural element in BVDV translation.

Abstract Background Retroviral Gag determines virus assembly at the plasma membrane and the formation of virus-like particles in intracellular multivesicular bodies. Thereby, retroviruses exploit by interaction with cellular partners the cellular machineries for vesicular transport in various ways. Results The retroviral Gag precursor protein drives assembly of murine leukaemia viruses (MLV) at the plasma membrane (PM) and the formation of virus like particles in multivesicular bodies (MVBs). In our study we show that caveolin-1 (Cav-1), a multifunctional membrane-associated protein, co-localizes with Gag in a punctate pattern at the PM of infected NIH 3T3 cells. We provide evidence that Cav-1 interacts with the matrix protein (MA) of the Gag precursor. This interaction is mediated by a Cav-1 binding domain (CBD) within the N-terminus of MA. Interestingly, the CBD motif identified within MA is highly conserved among most other γ-retroviruses. Furthermore, Cav-1 is incorporated into MLV released from NIH 3T3 cells. Overexpression of a GFP fusion protein containing the putative CBD of the retroviral MA resulted in a considerable decrease in production of infectious retrovirus. Moreover, expression of a dominant-negative Cav-1 mutant affected retroviral titres significantly. Conclusion This study demonstrates that Cav-1 interacts with MLV Gag, co-localizes with Gag at the PM and affects the production of infectious virus. The results strongly suggest a role for Cav-1 in the process of virus assembly.

Abstract Background Cholesterol-rich microdomains like lipid rafts were recently identified as regions within the plasma membrane, which play an important role in the assembly and budding of different viruses, e.g., measles virus and human immunodeficiency virus. For these viruses association of newly synthesized viral proteins with lipid rafts has been shown. Results Here we provide evidence for the association of the envelope protein (Env) of the 4070A isolate of amphotropic murine leukaemia virus (A-MLV) with lipid rafts. Using density gradient centrifugation and immunocytochemical analyses, we show that Env co-localizes with cholesterol, ganglioside GM1 and caveolin-1 in these specific regions of the plasma membrane. Conclusions These results show that a large amount of A-MLV Env is associated with lipid rafts and suggest that cholesterol-rich microdomains are used as portals for the exit of A-MLV.

Objective: To investigate the long-term outcomes of fornix reconstruction and cicatricial entropion repair in patients with ocular mucous membrane pemphigoid (MMP) and secondary MMP., Methods: Retrospective chart review of patients with MMP undergoing either fornix reconstruction (with amniotic membrane or buccal mucosal graft) or Wies cicatricial entropion repair between January 1, 2000, and September 1, 2020. Patients had a positive mucosal biopsy and (or) clinical features of MMP or secondary MMP. The primary outcome was overall success of fornix reconstruction based on fornix depth maintenance at latest follow-up. Secondary outcomes included resolution of trichiasis, visual acuity, and improvement of subjective symptoms., Results: Eight patients (10 eyes) with a diagnosis of MMP (3 males and 5 females; median age, 71 years) and 4 patients (4 eyes) with a diagnosis of secondary MMP (2 females and 2 male; median age, 87 years) were enrolled. Mean follow-up was 22.7 months (range, 0.3-87.5 months) for MMP patients and 15.4 months (range, 3.0-43.9 months) for secondary MMP patients. For MMP eyes, 30.0% underwent fornix reconstruction, 60.0% underwent entropion repair, and 10.0% received both. Re-formation of symblepharon and loss of fornix depth occurred in all MMP eyes at an average of 6.4 ± 7.0 months postoperatively, and trichiasis recurred in all patients at the last follow-up visit. In secondary MMP patients, 75.0% of the eyes showed recurrence of symblepharon, and 66.7% re-formed trichiasis. Both MMP and secondary MMP patients had short-term symptom improvements., Conclusions: Fornix reconstruction and cicatricial entropion repair in our cohort of MMP and secondary MMP patients resulted in short-term symptomatic improvement, but recurrence was seen, on average, at 6 months postoperatively., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia., Methods: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm., Results: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG., Discussion: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG., Classification of Evidence: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders., Trial Registration Information: ClinicalTrials.gov: NCT03049956.

Orbital metastases secondary to neuroendocrine tumors are exceedingly rare. We present a unique case of a 30-year-old female initially presenting with fever, chills, periorbital swelling, and painful proptosis. CT orbits revealed two ovoid-shaped ring-enhancing lesions in the right lateral and superior rectus muscles and clear sinuses, atypical for infectious post-septal cellulitis. Further work-up included serologic analysis, auto-immune panel, and MRI. Further imaging showed pseudocystic orbital lesions mimicking orbital cysticercosis. Additionally, given the bilateral nature of the lesions and patient's country of origin, this parasitic process was highly suspected. A course of albendazole and steroids led to resolution of symptoms. With a presentation at age 30, this is by far the youngest case reported in literature to date.

The Baltic Sea is among the most polluted seas worldwide. Anthropogenic contaminants are mainly introduced via riverine discharge and atmospheric deposition. Regional and international measures have successfully been employed to reduce concentrations of several legacy contaminants. However, current Baltic Sea monitoring programs do not address compounds of emerging concern. Hence, potentially harmful pharmaceuticals, UV filters, polar pesticides, estrogenic compounds, per- and polyfluoroalkyl substances, or naturally produced algal toxins are not taken into account during the assessment of the state of the Baltic Sea. Herein, we conducted literature searches based on systematic approaches and compiled reported data on these substances in Baltic Sea surface water and on methodological advances for sample processing and chemical as well as effect-based analysis of these analytically challenging marine pollutants. Finally, we provide recommendations for improvement of future contaminant and risk assessment in the Baltic Sea, which revolve around a combination of both chemical and effect-based analyses., (© 2021. The Author(s).)

Stable isotope labeling of pollutants is a valuable tool to investigate their environmental transport and degradation. For the globally most frequently used herbicide glyphosate, such studies have, so far, been hampered by the absence of an analytical standard for its labeled metabolite AMPA- 15 N, which is formed during the degradation of all commercially available glyphosate isotopologues. Without such a standard, detection and quantitation of AMPA- 15 N, e.g. with LC-MS/MS, is not possible. Therefore, a synthetic pathway to AMPA- 15 N from benzamide- 15 N via the hemiaminal was developed. AMPA- 15 N was obtained in sufficient yield and purity to be used as a standard compound for LC-MS/MS analysis. Suitable MS-detection settings as well as a calibration using the internal standard (IS) approach were established for Fmoc-derivatized AMPA- 15 N. The use of different AMPA isotopologues as IS was complicated by the parallel formation of [M+H] + and [M] +• AMPA-Fmoc precursor ions in ESI-positive mode, causing signal interferences between analyte and IS. We recommend the use of either AMPA- 13 C- 15 N, AMPA- 13 C- 15 N-D 2 or a glyphosate isotopologue as IS, as they do not affect the linearity of the calibration curve. As a proof of concept, the developed analysis procedure for AMPA- 15 N was used to refine the results from a field lysimeter experiment investigating leaching and degradation of glyphosate-2- 13 C- 15 N. The newly enabled quantitation of AMPA- 15 N in soil extracts showed that similar amounts (0.05 - 0.22 mg·kg -1 ) of the parent herbicide glyphosate and its primary metabolite AMPA persisted in the topsoil over the study period of one year, while vertical transport through the soil column did not occur for either of the compounds. The herein developed analysis concepts will facilitate future design and execution of experiments on the environmental fate of the herbicide glyphosate., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes., Methods: We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers., Results: Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05)., Conclusion: Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.

Purpose: To describe a technique for retrieving an inferomedially migrated Jones lacrimal tube., Methods: The distal end of the migrated Jones tube is visualized directly via the nose. The tip of an endoilluminator (23 Gauge Constellation Vision Systems) is bent to form a 45° to 60° angle using a mosquito forceps and inserted into the distal opening of the tube. The endoilluminator is used to push the tube upward toward the original medial canthal opening and limit downward displacement as the caruncular area is surgically explored. The light transilluminating the tube facilitates its visualization and retrieval in the caruncular area. A new tube may be threaded through the same passage, or if the ostium is traumatized, through a new passage., Results: This technique is time-efficient and has proven to be safe and successful in subsequent patients., Conclusions: The described technique aids in retrieving an inferomedially migrated Jones tube with minimal trauma to the surrounding structures., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: This study investigates the dart-throwing motion (DTM) by comparing an inertial measurement unit-based system previously validated for basic motion tasks with an optoelectronic motion capture system. The DTM is interesting as wrist movement during many activities of daily living occur in this movement plane, but the complex movement is difficult to assess clinically., Methods: Ten healthy subjects were recorded while performing the DTM with their right wrist using inertial sensors and skin markers. Maximum range of motion obtained by the different systems and the mean absolute difference were calculated., Results: In the flexion-extension plane, both systems calculated a range of motion of 100° with mean absolute differences of 8°, while in the radial-ulnar deviation plane, a mean absolute difference of 17° and range of motion values of 48° for the optoelectronic system and 59° for the inertial measurement units were found., Conclusions: This study shows the challenge of comparing results of different kinematic motion capture systems for complex movements while also highlighting inertial measurement units as promising for future clinical application in dynamic and coupled wrist movements. Possible sources of error and solutions are discussed.

Moyamoya (MM) disease is a chronic cerebrovascular disease that can lead to progressive stenosis of the terminal portions of the internal carotid arteries and their proximal branches. We sought to investigate and quantify retinal vascular changes in patients with MM vasculopathy (MMV) using optical coherence tomography angiography (OCTA) compared to healthy controls. Our findings reveal retinal microvascular changes in patients with MMV and highlights the potential of OCTA imaging for the detection of subclinical retinal pathology., (© 2021 Taylor & Francis Group, LLC.)

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Purpose: To evaluate the long-term efficacy and safety of topography-guided photorefractive keratectomy (TG-PRK) for postkeratoplasty refractive error correction., Methods: A retrospective interventional case series of 54 eyes of 50 patients who underwent previous corneal transplants. Unaided distance visual acuity (UDVA) and best corrected visual acuity (CDVA), manifest refraction, mean central keratometric value, mean keratometric astigmatism, and postoperative complications were reviewed., Results: Final follow-up was at mean 31 (±17) months. Sixteen point seven percent of eyes underwent more than 1 surface ablation. Mean UDVA improved from 0.96 ± 0.06 logarithm of the minimum angle of resolution (LogMAR) preoperatively to 0.46 ± 0.05 LogMAR of resolution at the final follow-up (Bonferroni, P < 0.0001). Mean UDVA improved by 4.4 Snellen lines. Improvement in CDVA was not significant, although a significant improvement was noted when eyes with preoperative CDVA <20/40 were analyzed separately (t test, P = 0.005). Mean astigmatism improved from -4.4 ± 0.26 D preoperatively to -2.4 ± 0.26 D at the final follow-up (Bonferroni, P < 0.0001), whereas mean SEQ improved from -2.5 ± 0.39 D preoperatively to -1.1 ± 0.25 D (Bonferroni, P = 0.02). In total, 9% at the preoperative visit and 55% at the final visit had less than 2 D of astigmatism, respectively. Keratometric astigmatism decreased from 5.24 ± 0.36 D preoperatively to 2.98 ± 0.34 D at the final follow-up (t test, P < 0.0001). No eyes developed clinically significant haze, 14.8% developed regression, and 13% had a reduction of 2 or more CDVA lines., Conclusions: Postkeratoplasty topography-guided photorefractive keratectomy has good long-term efficacy and safety, resulting in significant UDVA, refractive, and keratometric improvement. Regression can occur after the first year of treatment, emphasizing the importance of long-term follow-up.

The globally used herbicide glyphosate and its metabolite aminomethylphosphonic acid (AMPA) have not yet been reported to occur in the marine environment, presumably due to a lack of suitable analytical methods. In this study, we developed two new methods for the analysis of glyphosate and AMPA in seawater: a small-scale method, which includes an SPE cleanup step that minimizes salt-matrix effects during LC-MS/MS analysis, and a large-scale method that employs an additional SPE preconcentration step. Different SPE materials were evaluated for their suitability to enrich glyphosate and AMPA from saltwater and a molecularly imprinted polymer was selected. Both methods were validated in ultrapure water and environmental seawater. Achieved limits of detection with the small-scale method were 6 and 8 ng/L for glyphosate and AMPA, while the large-scale method achieved 0.12 and 0.22 ng/L, respectively. The small-scale method was used to analyze environmental samples from the Warnow Estuary in Germany. Glyphosate and AMPA could be successfully detected in the samples, but could not be measured beyond the saline estuary due to dilution and degradation effects. A set of samples from the western Baltic Sea was analyzed with the large-scale method. Glyphosate and AMPA could be detected in all Baltic Sea samples, especially at stations close to estuaries. To the best of our knowledge, this is the first report on the occurrence of glyphosate and AMPA in seawater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Timely and accurate diagnosis of myasthenia gravis, particularly in patients with fluctuating, isolated ocular involvement, remains challenging. Serological antibody testing and repetitive nerve stimulation of peripheral muscles usually have low sensitivity in these patients. Edrophonium testing may cause adverse events, single-fiber electromyography (SFEMG) is time-consuming and both tests are often unavailable outside specialized institutions. Repetitive ocular vestibular evoked myogenic potential (roVEMP) stimulation has recently been introduced to facilitate the diagnosis of myasthenia gravis. Similar to repetitive nerve stimulation, roVEMPs detect muscle decrements with the benefit of being non-invasive and allowing for direct measurement of the extraocular muscles. This review summarizes the clinical evidence of the diagnostic value of roVEMP for myasthenia. Prospective clinical trials have demonstrated high sensitivity and specificity. RoVEMPs are of particular interest in challenging myasthenia subgroups with isolated ocular involvement, negative serology, and/or negative conventional electrophysiological results. Optimal roVEMP repetition rates of 20-30 Hz have been identified. This promising novel diagnostic tool merits further attention and investigation to establish its value as a clinical test for myasthenia., (Copyright © 2020 Wirth, Fierz, Valko and Weber.)

Methylphosphonic acid (MPn) is suspected to play an important role in aquatic systems like rivers or the open ocean. To gain more insights into the importance of MPn, e.g., for the aquatic phosphorus cycle, an analytical method for its quantitative determination was developed. The method is based on the use of an isotopically-labelled internal standard and sample preparation including solid-phase extraction (SPE). Instrumental detection was done using GC-MS after derivatisation of MPn with N-tert-Butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). The study compares different isotopically-labelled compounds as well as different SPE-materials. As water samples with high salt content decrease the recovery of the chosen SPE-material, a desalting procedure using electrodialysis was implemented. Finally, water samples from different aquatic systems located at the German Baltic Sea coastal area were analysed to gain first insights into the relevance of MPn in these systems. MPn-concentrations in the low μg/L-range were detected., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To validate the repetitive ocular vestibular evoked myogenic potentials (RoVEMP) test for diagnostic use in myasthenia gravis (MG) and to investigate its value in diagnostically challenging subgroups., Methods: The RoVEMP test was performed in 92 patients with MG, 22 healthy controls, 33 patients with a neuromuscular disease other than MG (neuromuscular controls), 4 patients with Lambert-Eaton myasthenic syndrome, and 2 patients with congenital myasthenic syndrome., Results: Mean decrement was significantly higher in patients with MG (28.4% ± 32.2) than in healthy controls (3.2% ± 13.9; p < 0.001) or neuromuscular controls (3.8% ± 26.9; p < 0.001). With neuromuscular controls as reference, a cutoff of ≥14.3% resulted in a sensitivity of 67% and a specificity of 82%. The sensitivity of the RoVEMP test was 80% in ocular MG and 63% in generalized MG. The RoVEMP test was positive in 6 of 7 patients with seronegative MG (SNMG) with isolated ocular weakness. Of 10 patients with SNMG with negative repetitive nerve stimulation (RNS) results, 73% had an abnormal RoVEMP test. The magnitude of decrement was correlated with the time since the last intake of pyridostigmine (B = 5.40; p = 0.019)., Conclusions: The RoVEMP test is a new neurophysiologic test that, in contrast to RNS and single-fiber EMG, is able to measure neuromuscular transmission of extraocular muscles, which are the most affected muscles in MG. Especially in diagnostically challenging patients with negative antibody tests, negative RNS results, and isolated ocular muscle weakness, the RoVEMP test has a clear added value in supporting the diagnosis of MG., Classification of Evidence: This study provides Class III evidence that RoVEMP distinguishes MG from other neuromuscular diseases., (© 2020 American Academy of Neurology.)

Glyphosate (GLYP), the globally most important herbicide, may have effects in various compartments of the environment such as soil and water. Although laboratory studies showed fast microbial degradation and a low leaching potential, it is often detected in various environmental compartments, but pathways are unknown. Therefore, the objective was to study GLYP leaching and transformations in a lysimeter field experiment over a study period of one hydrological year using non-radioactive 13 C 2 - 15 N-GLYP labelling and maize cultivation. 15 N and 13 C were selectively measured using isotopic ratio mass spectrometry (IR-MS) in leachates, soil, and plant material. Additionally, HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) was used for quantitation of GLYP and its main degradation product aminomethylphosphonic acid (AMPA) in different environmental compartments (leachates and soil). Results show low recoveries for GLYP (< 3%) and AMPA (< level of detection) in soil after the study period, whereas recoveries of 15 N (11-19%) and 13 C (23-54%) were higher. Time independent enrichment of 15 N and 13 C and the absence of GLYP and AMPA in leachates indicated further degradation. 15 N was enriched in all compartments of maize plants (roots, shoots, and cobs). 13 C was only enriched in roots. Results confirmed rapid degradation to further degradation products, e.g., 15 NH 4 + , which plausibly was taken up as nutrient by plants. Due to the discrepancy of low GLYP and AMPA concentrations in soil, but higher values for 15 N and 13 C after the study period, it cannot be excluded that non-extractable residues of GLYP remained and accumulated in soil.