ICON 2023: International Scientific Tendinopathy Symposium Consensus - the core outcome set for Achilles tendinopathy (COS-AT) using a systematic review and a Delphi study of professional participants and patients.

To develop a core outcome set for Achilles tendinopathy (COS-AT) for use in clinical trials we performed a five-step process including (1) a systematic review of available outcome measurement instruments, (2) an online survey on truth and feasibility of the available measurement instruments, (3) an assessment of the methodological quality of the selected outcome measurement instruments, (4) an online survey on the outcome measurement instruments as COS and (5) a consensus in-person meeting. Both surveys were completed by healthcare professionals and patients. The Outcome Measures in Rheumatology guidelines with a 70% threshold for consensus were followed. We identified 233 different outcome measurement instruments from 307 included studies; 177 were mapped within the International Scientific Tendinopathy Symposium Consensus core domains. 31 participants (12 patients) completed the first online survey (response rate 94%). 22/177 (12%) outcome measurement instruments were deemed truthful and feasible and their measurement properties were evaluated. 29 participants (12 patients) completed the second online survey (response rate 88%) and three outcome measurement instruments were endorsed: the Victorian Institute of Sports Assessment-Achilles questionnaire, the single-leg heel rise test and evaluating pain after activity using a Visual Analogue Scale (VAS, 0-10). 12 participants (1 patient) attended the final consensus meeting, and 1 additional outcome measurement instrument was endorsed: evaluating pain during activity/loading using a VAS (0-10). It is recommended that the identified COS-AT will be used in future clinical trials evaluating the effectiveness of an intervention. This will facilitate comparing outcomes of intervention strategies, data pooling and further progression of knowledge about AT. As COS-AT is implemented, further evidence on measurement properties of included measures and new outcome measurement instruments should lead to its review and refinement.

Gender-Based Survey Analysis of Research and Mentoring in Interventional Radiology.

PURPOSE: This study sought to define gender-related differences in attitudes, perceptions, and aspirations among trainees interested in interventional radiology (IR) and to analyze their experiences in research and mentorship. MATERIALS AND METHODS: A cross-sectional survey study was conducted among the members of the Society of Interventional Radiology Resident, Fellow, and Student section and Medical Student section in the summer of 2020. The anonymous, internally validated 27-item survey assessed demographics, research attitudes and experiences, mentorship, and career aspirations. Descriptive statistics were calculated using Fisher exact analyses and Student t-tests. The institutional review board approved the protocols for this study. RESULTS: Of 105 respondents who indicated their gender, 30% were women and 70% were men. Although both genders reported similar levels of research experience, female trainees were less likely to feel valued and encouraged by their institution to engage in research (2.79 out of 4 vs 3.16 out of 4, P = .02) and were less likely to indicate that their program required them to participate in research (2.47 vs 3.06, P = .01). Female residents and fellows reported more difficulty in finding a mentor (2.88 vs 3.28, P = .04) and received less mentorship relating to IR education (29% vs 64%, P = .002). CONCLUSIONS: This work provides a perspective on the perceived obstacles faced by female trainees in pursuing research and finding effective mentorship in the field of IR. These data may guide future interventions to boost interest and engagement in IR research and residency programs in a way that promotes gender diversity and equity in the field.

Transitioning the IR Clinic to Telehealth: A Single-Center Experience during the COVID-19 Pandemic.

Telehealth has not previously been widely implemented as a result of regulatory and reimbursement concerns; however, in the current national emergency of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services has relaxed many of its rules, allowing increased adoption of telehealth services, improving the safety and access of outpatient health care. A complete understanding of the regulatory requirements, technologic options, and billing processes of telehealth is required to initiate a successful clinic. A model is presented here based on a single institution's experience with implementing telehealth in the outpatient interventional radiology clinic.

Revisiting autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) mutations in the nicotinic acetylcholine receptor reveal an increase in efficacy regardless of stochiometry.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a genetic form of epilepsy that is caused by mutations in several genes, including genes encoding for the α4 and ß2 subunits of the nicotinic acetylcholine (nACh) receptor. Pentameric α4ß2 nACh receptors are the most abundant nicotinic receptor in the mammalian brain and form two stoichiometries, the (α4)3(ß2)2 and (α4)2(ß2)3 receptors that differ in their physiological and pharmacological properties. The purpose of this study was to investigate how ADNFLE mutations ß2V287M, ß2V287L or α4T293I manifest themselves in different receptor stoichiometries. We expressed wild-type and mutant receptors in Xenopus oocytes and measured the response to ACh and other agonists at both receptor stoichiometries. For all three mutations, the efficacy of ACh at (α4)2(ß2)3 receptors was increased. At (α4)3(ß2)2 receptors, the efficacy of activation was increased both when two molecules of agonist, either ACh or the site-selective agonist sazetidine-A, were bound at the α4-ß2 interfaces, and when a third ACh molecule was bound at the α4-α4 site. Regardless of stoichiometry, the mutations increased the current elicited by low concentrations of ACh. Further, the smoking cessation agents, nicotine, varenicline and cytisine increased activation of mutant (α4)3(ß2)2 receptors, while only nicotine increased activation of mutant (α4)2(ß2)3 receptors. Chronic exposure of all agonists reduced ACh-activation levels at low and high ACh concentrations. From this, we concluded that mutations that cause ADNFLE manifest themselves in a change in efficacy regardless of the stoichiometry of the receptor.

Radiologic versus Endoscopic Placement of Gastrostomy Tube: Comparison of Indications and Outcomes at a Tertiary Referral Center.

OBJECTIVES: Percutaneous gastrostomy tube placement is performed in patients requiring long-term enteral nutrition. Although both endoscopic and fluoroscopic techniques may be used, there are inherent risks and potential complications associated with both procedures that are not generally known to referring physicians. The purpose of this study was to compare and contrast indications for placement and procedurally related complications between fluoroscopic and endoscopic gastrostomy tubes techniques at a tertiary care facility. METHODS: A retrospective cohort study was performed. All consecutive patients with either percutaneous endoscopic (PEG) or percutaneous radiologic (PRG) gastrostomy tube placement between October 2011 and January 2013 were eligible for inclusion. Basic demographic information, American Society of Anesthesiologists score, procedure indication, laboratory data, and use of anticoagulation were recorded. Both direct and indirect procedural complications were documented if they occurred 30 days after gastrostomy tube placement, and were classified and scored based on severity and need for further intervention. RESULTS: A total of 297 patients met the inclusion criteria, 150 of whom had gastrostomy tubes placed fluoroscopically and 147 of whom had them placed endoscopically. There was no statistically significant difference in direct complications within the first 30 days (PEG 6.8% vs PRG 8%); however, the type of complication observed varied between the two groups. Although superficial wound infections and buried bumpers were more common in the PEG group, bleeding was more common in the PRG group. CONCLUSIONS: Placement of gastrostomy tubes either endoscopically or fluoroscopically is relatively safe with similar indications. Although the complication rate between the two groups was not significant, the types of procedural complications observed did vary.

Effect of Copper and Other Trace Metal Addition to Pulp and Paper Wastewater.

Porous pots were used to mimic, on a laboratory scale, an industrial activated sludge plant from a thermomechanical pulp and news print paper mill. Trace metal additions of Ca, Co, Cu, Fe(III), and Mg were found to improve chemical oxygen demand removal from 82% to 86 to 87%. Copper (0.1 to 1.0 mg/L) was also found to be beneficial in significantly inhibiting the growth of filamentous bacteria, contributing to a reduction of 20 to 45% in sludge volume index (SVI) with improved settle ability and decreased bulking. However, at levels of 1.0 mg/L and higher, the concentration of Cu in the porous pot effluent would potentially exceed guidelines for receiving waters. The fate and impact of Cu was affected by the presence of other trace metals, in particular Mg and Ca. The addition of Mg or Ca along with 0.5 mg/L Cu increased the amount of Cu in the aqueous phase to levels that would potentially exceed government environmental guidelines. Calcium addition was also found to inhibit the effect of Cu in reducing filamentous bacteria and SVI.

Covalent trapping of methyllycaconitine at the α4-α4 interface of the α4ß2 nicotinic acetylcholine receptor: antagonist binding site and mode of receptor inhibition revealed.

The α4ß2 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain and are implicated in a variety of physiological processes. There are two stoichiometries of the α4ß2 nAChR, (α4)2(ß2)3 and (α4)3(ß2)2, with different sensitivities to acetylcholine (ACh), but their pharmacological profiles are not fully understood. Methyllycaconitine (MLA) is known to be an antagonist of nAChRs. Using the two-electrode voltage clamp technique and α4ß2 nAChRs in the Xenopus oocyte expression system, we demonstrate that inhibition by MLA occurs via two different mechanisms; that is, a direct competitive antagonism and an apparently insurmountable mechanism that only occurs after preincubation with MLA. We hypothesized an additional MLA binding site in the α4-α4 interface that is unique to this stoichiometry. To prove this, we covalently trapped a cysteine-reactive MLA analog at an α4ß2 receptor containing an α4(D204C) mutation predicted by homology modeling to be within reach of the reactive probe. We demonstrate that covalent trapping results in irreversible reduction of ACh-elicited currents in the (α4)3(ß2)2 stoichiometry, indicating that MLA binds to the α4-α4 interface of the (α4)3(ß2)2 and providing direct evidence of ligand binding to the α4-α4 interface. Consistent with other studies, we propose that the α4-α4 interface is a structural target for potential therapeutics that modulate (α4)3(ß2)2 nAChRs.

Development of matrix-specific standards for LA-ICP-MS zinc analysis in sand flathead (Platycephalus bassensis).

The use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to analyse soft tissues is limited because of the lack of suitable certified reference materials resulting in difficulties with calibration. In this study, several laboratory-prepared thin agarose sections were tested as matrix-specific standards. Our results showed 1 mm thin agarose sections were suitable as calibration standards for LA-ICP-MS Zn analyses in fish muscle, especially when the signal intensity of 66Zn was normalised to 13C. The thin agarose standard sections were used for LA-ICP-MS Zn analyses in the muscle of melanised and non-melanised sand flathead collected from a polluted estuary and assigned with different melanisation scores. Zn levels in melanised regions of fish muscle were determined to be significantly higher than non-melanised regions across all melanisation scores, though Zn levels in the melanised regions of muscle were not significantly different between sand flathead with different melanisation scores. In non-melanised regions of muscle from fish with melanisation and fish unaffected by melanisation, Zn levels were around baseline levels. Overall, this study has successfully developed matrix-specific standards for LA-ICP-MS analysis of soft tissues, thus allowing broader application of this analytical technique in future environmental pollution studies.

An optimised 3 M KCl salt-bridge technique used to measure and validate theoretical liquid junction potential values in patch-clamping and electrophysiology.

Accurate potential measurements in electrophysiological experiments require correction for liquid junction potentials (LJPs), and, in patch-clamping especially, these can often be ~5-10 mV or more. They can be either calculated, if ion mobilities are known, or measured directly. We describe an optimised system to directly measure LJPs with a patch-clamp amplifier, using as a reference electrode, a freshly-cut 3 M KCl-agar salt-bridge (in polyethylene tubing) with its tip cut off by at least 5 mm during solution changes to eliminate its solution-history-dependent effects. We quantify such history-dependent effects and complement this with a de-novo theoretical analysis of salt diffusion to and from the salt-bridge. Our analysis and experimental results validate the optimised methodology for measuring LJPs, and the use of the Henderson equation for accurately calculating them. The use of this equation is also assessed and generally validated in the light of rigorous Nernst-Planck-Poisson and other numerical simulations and analytical studies of LJPs over recent decades. Digitizing, recording and amplifying the measured potentials increases their accuracy. The measured potentials still need correction for small, well-defined calculable, shifts in LJPs at the 3 M KCl-agar reference. Using this technique, we have measured changes in LJPs for diluted solutions of NaCl, LiCl, KCl, CsCl and NaF, obtaining excellent agreement within ±0.1 mV of predicted values, calculated using ion activities. Our de novo LJP measurements of biionic combinations of the above undiluted salts, and NaI and NaF (with halide anions I⁻ and F⁻), generally also gave excellent agreement with predicted values.

Mechanistic investigation of the oxidation of hydrazides: implications for the activation of the TB drug isoniazid.

Aryl hydrazides are oxidised to acyl radicals through a mechanism involving diimide intermediates that are prone to nucleophilic acyl substitution. This oxidation occurs regardless of the oxidant involved, however there is no evidence that the acyl radical formed undergoes further oxidation to the corresponding acylium ion, even in the presence of strong oxidants. This study may provide insight into the mechanism of isoniazid resistance in Mycobacterium tuberculosis.

E-health in low- and middle-income countries: findings from the Center for Health Market Innovations.

OBJECTIVE: To describe how information communication technology (ICT) is being used by programmes that seek to improve private sector health financing and delivery in low- and middle-income countries, including the main uses of the technology and the types of technologies being used. METHODS: In-country partners in 16 countries directly searched systematically for innovative health programmes and compiled profiles in the Center for Health Market Innovations' database. These data were supplemented through literature reviews and with self-reported data supplied by the programmes themselves. FINDINGS: In many low- and middle-income countries, ICT is being increasingly employed for different purposes in various health-related areas. Of ICT-enabled health programmes, 42% use it to extend geographic access to health care, 38% to improve data management and 31% to facilitate communication between patients and physicians outside the physician's office. Other purposes include improving diagnosis and treatment (17%), mitigating fraud and abuse (8%) and streamlining financial transactions (4%). The most common devices used in technology-enabled programmes are phones and computers; 71% and 39% of programmes use them, respectively, and the most common applications are voice (34%), software (32%) and text messages (31%). Donors are the primary funders of 47% of ICT-based health programmes. CONCLUSION: Various types of ICT are being employed by private organizations to address key health system challenges. For successful implementation, however, more sustainable sources of funding, greater support for the adoption of new technologies and better ways of evaluating impact are required.

The use of image analysis techniques for the study of muscle melanisation in sand flathead (Platycephalus bassensis).

Muscle melanisation in sand flathead is visible as black spots in the normally white flesh of fish. It is widespread in Tasmania, including at the Tamar Estuary, with increasing frequency of reporting by recreational fishers. The phenomenon is more prevalent in areas impacted by heavy metal pollution and has been linked to heavy metal accumulation. In this study, image processing software ImageJ was employed to study the phenomenon and to establish an objective rating system. A longitudinal profile plot was used to study the greying of the fillet. The degree of melanisation was rated based on the percentage surface area melanised on the surface and in transverse sections of fillets. A muscle melanisation scoring system for sand flathead was established based on visual interpretation using the macroscopic melanisation scoring criteria: melanisation scores 0 = <0.5%, 1 = 0.5-5%, 2 = 5-20%, and 3 = >20% (% = melanised surface area in proportion to the whole fillet). A refined image analysis technique was developed to quantify the percentage of melanised muscle surface area and the muscle melanisation scoring system was statistically validated. Sand flathead fillet with higher melanisation score was shown to be linked to increased intensity of greyness and greater numbers and size of black spots on the surface of fillets and within the flesh. The greying and black spots were primarily concentrated at the anterior region of fillet and around the dorsal vertebrae zone on transverse section of fillets. Overall, findings from this study established the use of image analysis techniques to validate visual inspection and to give a standardised and objective method to determine the degree of melanisation in sand flathead. As muscle melanisation appears to be linked to heavy metal pollution, the standardised scoring system would facilitate future research for environmental pollution and monitoring purposes.

Mentorship in Interventional Radiology: Addressing Obstacles to Pursuing Research and Innovation Among IR Trainees.

RATIONALE AND OBJECTIVES: To ascertain the perceived obstacles that medical students and Interventional Radiology (IR) residents face performing IR research during training and incorporating research into their future careers. MATERIALS AND METHODS: The study was reviewed and exempt from Institutional Review Board review. Participants' attitudes and perceived barriers toward performing IR research, and experience with mentorship in IR were assessed using a 27-item survey sent to all members of the Society of Interventional Radiology Resident, Fellow and Student (SIR-RFS, n = 445), and Medical Student Council (SIR-MSC, n = 267) sections between July and September 2020. Descriptive statistics were computed for all assessed categorical variables. Fisher's exact tests were performed to measure the significance of association between categorical variables. RESULTS: Of the 712 students and residents surveyed, 151 (∼21%) responded. Of respondents, 100% reported that conducting research is important to advancing the field of IR. The highest ranked factors and obstacles to performing IR research were increased clinical demands (67.9%), lack of time (46.2%), lack of institutional support (41.5%), and lack of research experience (35.8%). Interestingly, those with a mentor were more likely to report an interest in pursuing a career in IR compared to those without a mentor (98.6% vs 41.0%, p < 0.0001). Furthermore, those with a mentor were more likely to report an interest in pursuing IR research compared to those without a mentor (32.5% vs 14.4%, p < 0.0001). CONCLUSION: There are many obstacles to performing IR research. Strong mentorship is an avenue to address these deterrents. The deployment of mentorship programs in IR is needed to ensure trainees can overcome the barriers outlined in this study and successfully pursue research careers in IR.

ICON 2020-International Scientific Tendinopathy Symposium Consensus: A Systematic Review of Outcome Measures Reported in Clinical Trials of Achilles Tendinopathy.

BACKGROUND: Nine core domains for tendinopathy have been identified. For Achilles tendinopathy there is large variation in outcome measures used, and how these fit into the core domains has not been investigated. OBJECTIVE: To identify all available outcome measures outcome measures used to assess the clinical phenotype of Achilles tendinopathy in prospective studies and to map the outcomes measures into predefined health-related core domains. DESIGN: Systematic review. DATA SOURCES: Embase, MEDLINE (Ovid), Web of Science, CINAHL, The Cochrane Library, SPORTDiscus and Google Scholar. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Clinical diagnosis of Achilles tendinopathy, sample size ≥ ten participants, age ≥ 16 years, and the study design was a randomized or non-randomized clinical trial, observational cohort, single-arm intervention, or case series. RESULTS: 9376 studies were initially screened and 307 studies were finally included, totaling 13,248 participants. There were 233 (177 core domain) different outcome measures identified across all domains. For each core domain outcome measures were identified, with a range between 8 and 35 unique outcome measures utilized for each domain. The proportion of studies that included outcomes for predefined core domains ranged from 4% for the psychological factors domain to 72% for the disability domain. CONCLUSION: 233 unique outcome measures for Achilles tendinopathy were identified. Most frequently, outcome measures were used within the disability domain. Outcome measures assessing psychological factors were scarcely used. The next step in developing a core outcome set for Achilles tendinopathy is to engage patients, clinicians and researchers to reach consensus on key outcomes measures. PROSPERO REGISTRATION: CRD42020156763.

Peripheral injury induces long-term sensitization of defensive responses to visual and tactile stimuli in the squid Loligo pealeii, Lesueur 1821.

Survivable injuries are a common yet costly experience. The ability to sense and respond to noxious stimuli is an almost universal trait, and prolonged behavioral alterations, including sensitization to touch and other stimuli, may function to ameliorate fitness costs associated with injury. Cephalopods can modify their behavior by learned association with noxious electric shock, but non-associative alterations of behavioral responses after tissue injury have not been studied. The aim of this study was to make the first systematic investigations in any cephalopod of behavioral responses and alterations elicited by explicit, minor injury. By testing responsiveness in the longfin squid, Loligo pealeii, to the approach and contact of an innocuous filament applied to different parts of the body both before and after injury to the distal third of one arm, we show that a cephalopod expresses behavioral alterations persisting for at least 2 days after injury. These alterations parallel forms of nociceptive plasticity in other animals, including general and site-specific sensitization to tactile stimuli. A novel finding is that hyper-responsiveness after injury extends to visual stimuli. Injured squid are more likely to employ crypsis than escape in response to an approaching visual stimulus shortly after injury, but initiate escape earlier and continue escape behaviors for longer when tested from 1 to 48 h after injury. Injury failed to elicit overt wound-directed behavior (e.g. grooming) or change hunting success. Our results show that long-lasting nociceptive sensitization occurs in cephalopods, and suggest that it may function to reduce predation risk after injury.

Interrelation between sulphur and conductive materials and its impact on ammonium and organic pollutants removal in electroactive wetlands.

This investigation is the first of its kind to evaluate the interrelation of sulphate (SO42-) with conductive materials as well as their individual and synergetic effects on the removal of ammonium and organic pollutants in electroactive wetlands, also known as constructed wetland (CW) - microbial fuel cell (MFC). The role of MFC components in CW was investigated to treat the sulphate containing wastewater under a long-term operation without any toxicity build-up in the system. A comparative study was also performed between CW-MFC and CW, where sulphate containing wastewater (S-replete) and without sulphate wastewater (S-deplete) was assessed. The S-replete showed high NH4+ removal than the S-deplete, and the requesnce of removal was: CW-MFC-replete>CW-MFC-deplete>CW-replete>CW-deplete. The chemical oxygen demand (COD) removal was high in the case of CW-MFC-replete, and the sequence of removal was CW-MFC-replete>CW-MFC-deplete>CW-deplete>CW-replete. X-ray photon spectroscopic study indicates 0.84% sulphur accumulation in CW-MFC-replete and 2.49% in CW-replete, indicating high sulphur precipitation in CW without the MFC component. The high relative abundance of class Deltaproteobacteria (7.3%) in CW-MFC-replete along with increased microbial diversity (Shannon index=3.5) rationalise the symbiosis of sulphate reducing/oxidising microbes and its impact on the treatment performance and electrochemical activity.

Influence of applied potential on treatment performance and clogging behaviour of hybrid constructed wetland-microbial electrochemical technologies.

A two-stage hybrid Constructed Wetland (CW) integrated with a microbial fuel cell (MFC), and microbial electrolysis cell (MEC) has been assessed for treatment performance and clogging assessment and further compared with CW. The CW-MEC was operated with applied potential to the working electrode and compared with the performance of naturally adapted redox potential of the CW-MFC system. A complex synthetic municipal wastewater was used during the study, which was composed of trace metals, organics, inorganics, and dye. The study demonstrated that providing a constant potential to the working electrode in CW-MEC has resulted in high treatment performance and reduced sludge generation. The maximum chemical oxygen demand (COD), ammonium (NH4+), and phosphate (PO43-) removal achieved during treatment by CW-MEC at 24 h hydraulic retention time was 89 ± 6%, 72 ± 6% and 93 ± 2%, respectively. ICP-MS results indicated that trace metal removals were also higher in CW-MEC than in CW alone (p < 0.05). At the end of the experiment, significant volumetric change (total volume of the microcosm) occurred in CW (1.3 L), which indicates high sludge generation, whereas it was lesser in CW-MEC (0.3 L) and in CW-MFC (0.5 L). Further, Energy Dispersive X-ray (EDX) spectroscopy results indicated low levels of metal precipitation in the CW-MEC system. Based on the Shannon diversity index, the CW-MEC was assessed to be characterised by high species richness and diversity. The observations from this study indicate that the applied potential at the working electrode has a significant impact on treatment performance and clogging behaviour of the system.