In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

A framework for automated gene selection in genomic applications.

PURPOSE: An efficient framework to identify disease-associated genes is needed to evaluate genomic data for both individuals with an unknown disease etiology and those undergoing genomic screening. Here, we propose a framework for gene selection used in genomic analyses, including applications limited to genes with strong or established evidence levels and applications including genes with less or emerging evidence of disease association. METHODS: We extracted genes with evidence for gene-disease association from the Human Gene Mutation Database, OMIM, and ClinVar to build a comprehensive gene list of 6,145 genes. Next, we applied stringent filters in conjunction with computationally curated evidence (DisGeNET) to create a restrictive list limited to 3,929 genes with stronger disease associations. RESULTS: When compared to manual gene curation efforts, including the Clinical Genome Resource, genes with strong or definitive disease associations are included in both gene lists at high percentages, while genes with limited evidence are largely removed. We further confirmed the utility of this approach in identifying pathogenic and likely pathogenic variants in 45 genomes. CONCLUSION: Our approach efficiently creates highly sensitive gene lists for genomic applications, while remaining dynamic and updatable, enabling time savings in genomic applications.

Investigating lipid headgroup composition within epithelial membranes: a systematic review.

Membrane lipid composition is often quoted within the literature, but with very little insight into how or why these compositions vary when compared to other biological membranes. One prominent area that lacks understanding in terms of rationale for lipid variability is the human gastro-intestinal tract (GIT). We have carried out a comprehensive systematic literature search to ascertain the key lipid components of epithelial membranes, with a particular focus on addressing the human GIT and to use compositional data to understand structural aspects of biological membranes. Both bacterial outer membranes and the human erythrocyte membrane were used as a comparison for the mammalian [epithelial] membranes and to understand variations in lipid presence. We show that phosphatidylcholine (PC) lipid types tend to dominate (33%) with phosphatidylethanolamines (PE) and cholesterol having very similar abundances (25 and 23% respectively). This systematic review presents a detailed insight into lipid headgroup composition and roles in various membrane types, with a summary of the distinction between the major lipid bilayer forming lipids and how peripheral lipids regulate charge and fluidity. The variety of lipids present in biological membranes is discussed and rationalised in terms function as well as cellular position.

External carotid artery pseudoaneurysm following upper respiratory infection masquerading as a pharyngeal abscess in an 8-month-old.

Pseudoaneurysms are very rare with an incidence of less than 0.1% in the pediatric population. Approximately 30 cases of carotid artery aneurysms in children have been published in the literature, usually affecting children over one year of age. We present one of the youngest cases in the literature; the patient is an 8-month old female with a strep throat infection complicated by pseudoaneurysm development of the external carotid artery. Because of the rarity of these lesions, there is little known regarding the types of clinical presentation and management. They are commonly the result of direct arterial trauma; however, they can also occur secondary to infection, connective tissue disease or arteritis. We are presenting a case with a highly atypical presentation. When present, pseudoaneurysms harbor the potential risk of life-threatening hemorrhage and warrant immediate management. It is important to be aware of cases and the treatment modalities used to guide future diagnosis and planning.

EPOS 4 Patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Neurofilament-light in former athletes: a potential biomarker of neurodegeneration and progression.

BACKGROUND/OBJECTIVE: This study aimed to evaluate serum neurofilament light chain (NF-L) levels in former professional contact sports athletes with multiple concussions (ExPro) as a potential biomarker of neurodegeneration and predictor of white-matter (WM) abnormality progression. METHODS: Concentrations of NF-L in the serum of fifty-two cognitively normal ExPro and twenty-one healthy controls (HC) with no history of concussions were measured using single molecule array (Simoa) technology. Both groups underwent neuroimaging at the time of serum collection. Eighteen of the participants in the ExPro underwent follow-up imaging after 2 years. RESULTS: Levels of serum NF-L were not significantly different between the ExPro and HC. However, in the ExPro group, NF-L levels were positively correlated with the mean diffusivity (MD) of corpus callosum (CC) and fornix, and total ventricular volume. Moreover, NF-L levels in the ExPro group at the first visit were positively correlated with the amount of increase in CC MD at the 2-year follow-up. CONCLUSIONS: NF-L levels reflect neuronal changes in the ExPro group and predict the extent of decrease in white matter integrity over time. Serum NF-L might be a biomarker of neurodegeneration and WM abnormality progression in ExPro.

Dynamic contrast-enhanced ultrasound improves diagnostic performance in endometrial cancer staging.

OBJECTIVES: To compare the sensitivity and specificity of conventional two-dimensional transvaginal ultrasound/power Doppler (2D-TVU/PD) alone and 2D-TVU/PD combined with dynamic contrast-enhanced ultrasound (DCE-US) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) in women with endometrial cancer (EC), and to assess the association of DCE-US semiquantitative and qualitative variables with International Federation of Gynecology and Obstetrics (FIGO) Stage ≥ IB and 'high-risk' cancer. METHODS: This was a prospective study of 101 consecutive women with biopsy-confirmed EC, undergoing expert ultrasound examination at Karolinska University Hospital, a tertiary referral center. All consenting women underwent DCE-US using a 1.5-2.5-mL intravenous bolus of SonoVue contrast agent, as well as conventional 2D-TVU/PD examination. DCE-US videoclips were analyzed with regard to filling (global or focal), wash-in (prior, simultaneous or after) and wash-out (global or focal) patterns of the contrast agent in the tumor compared with the surrounding tissue, as well as semiquantitative DCE-US parameters (wash-in slope, time-to-peak, peak intensity and area under the time-intensity curve (TIC)) obtained from a TIC. The study cohort was compared with a control cohort of women with EC examined at our center according to the International Endometrial Tumor Analysis protocol using 2D-TVU/PD only, matched at a ratio of 3:1 for FIGO stage and grade. The sensitivity and specificity of 2D-TVU/PD alone in the control cohort and in combination with DCE-US in the study cohort in the diagnosis of deep MI, CSI and high-risk cancer (defined as FIGO Stage ≥ IB and/or Grade 3 endometrioid and/or non-endometrioid histology) were compared, using pathological evaluation after hysterectomy as the 'gold standard'. RESULTS: After exclusions, 93 women were included in the study cohort and were matched to 279 women in the control cohort. The prevalence of FIGO Stage IA, Grade 1-2 EC was 52% in both cohorts. The sensitivity of 2D-TVU/PD with DCE-US in the study cohort was higher than that of 2D-TVU/PD alone in the control cohort in diagnosing both deep MI (0.74 vs 0.62; P = 0.036) and CSI (0.75 vs 0.51; P < 0.001), whereas the specificity was not significantly different (0.87 vs 0.85 and 0.96 vs 0.95, respectively). Compared with 2D-TVU/PD alone, the specificity of 2D-TVU/PD with DCE-US was higher in detecting high-risk cancer (0.94 vs 0.85; P = 0.024) but the sensitivity did not differ (0.73 vs 0.71). High-risk cancer and FIGO Stage ≥ IB were characterized by a 'focal' filling pattern, with a 'prior' wash-in pattern and a 'focal' wash-out pattern on subjective assessment of DCE-US videoclips. All semiquantitative DCE-US parameters were significantly predictive of FIGO Stage ≥ IB but not of high-risk cancer, despite a clear trend. CONCLUSIONS: Compared with 2D-TVU/PD alone, combining 2D-TVU/PD with DCE-US can significantly improve the detection of deep MI and CSI in women with EC, without increasing the false-positive rate. It can also improve the correct classification of high-risk disease, mainly by increasing specificity, thereby possibly reducing the number of unnecessarily extensive surgeries by almost 10%. Semiquantitative DCE-US parameters, as well as a 'focal' filling pattern, endometrial wash-in prior to the myometrium and a 'focal' wash-out pattern, are all associated with more advanced disease. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Efficacy of transversus abdominis plane (TAP) block in colorectal surgery: a systematic review and meta-analysis.

BACKGROUND: Multimodal opioid-sparing analgesia is a key component of the enhanced recovery after surgery (ERAS) protocol for postoperative pain management. Transversus abdominis plane (TAP) block has contributed to the implementation of this approach in different kinds of surgical procedures. The aim of this study was to evaluate the efficacy of TAP block and its impact on recovery in colorectal surgery. METHODS: A comprehensive literature search of the PubMed, Embase, and Scopus databases was conducted. Studies that compared TAP block to a control group (no TAP block or placebo) after colorectal resections were included. The effects of TAP block in patients undergoing colorectal surgery were assessed, including the technical aspects of the procedure. Two measures were used to evaluate the effectiveness of postoperative pain control: a numeric pain rating score at rest and on coughing or movement at 24 h following surgery and the opioid requirement at 24 h. Clinical aspects of recovery were postoperative ileus, surgical site infection, postoperative nausea and vomiting, and length of hospital stay. RESULTS: Sixteen studies were included in the analysis. Data showed that TAP block is a safe procedure associated with a significant reduction in the pain score at rest [WMD - 0.91 (95% CI - 1.56; - 0.27); p < 0.05] and on coughing or movement [WMD - 0.36 (95% CI - 0.72; - 0.01); p < 0.05] at 24 h after surgery and a significant decrease in morphine consumption in the TAP block group the day after surgery [WMD - 2.07 (95% CI - 2.63; - 1.51); p < 0.001]. CONCLUSIONS: TAP block appears to provide both an effective analgesia and a significant reduction in opioid use on the first postoperative day after colorectal surgery. Its use does not seem to lead to increased postoperative complications.

Toward a clinical antifungal peptoid: Investigations into the therapeutic potential of AEC5.

Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Existing antifungal treatment plans have high mammalian toxicity and increasing drug resistance, demonstrating the dire need for new, nontoxic therapeutics. Antimicrobial peptoids are one alternative to combat this issue. Our lab has recently identified a tripeptoid, AEC5, with promising efficacy and selectivity against C. neoformans. Here, we report studies into the broad-spectrum efficacy, killing kinetics, mechanism of action, in vivo half-life, and subchronic toxicity of this compound. Most notably, these studies have demonstrated that AEC5 rapidly reduces fungal burden, killing all viable fungi within 3 hours. Additionally, AEC5 has an in vivo half-life of 20+ hours and no observable in vivo toxicity following 28 days of daily injections. This research represents an important step in the characterization of AEC5 as a practical treatment option against C. neoformans infections.

An eye tracking study of bloodstain pattern analysts during pattern classification.

Bloodstain pattern analysis (BPA) is the forensic discipline concerned with the classification and interpretation of bloodstains and bloodstain patterns at the crime scene. At present, it is unclear exactly which stain or pattern properties and their associated values are most relevant to analysts when classifying a bloodstain pattern. Eye tracking technology has been widely used to investigate human perception and cognition. Its application to forensics, however, is limited. This is the first study to use eye tracking as a tool for gaining access to the mindset of the bloodstain pattern expert. An eye tracking method was used to follow the gaze of 24 bloodstain pattern analysts during an assigned task of classifying a laboratory-generated test bloodstain pattern. With the aid of an automated image-processing methodology, the properties of selected features of the pattern were quantified leading to the delineation of areas of interest (AOIs). Eye tracking data were collected for each AOI and combined with verbal statements made by analysts after the classification task to determine the critical range of values for relevant diagnostic features. Eye-tracking data indicated that there were four main regions of the pattern that analysts were most interested in. Within each region, individual elements or groups of elements that exhibited features associated with directionality, size, colour and shape appeared to capture the most interest of analysts during the classification task. The study showed that the eye movements of trained bloodstain pattern experts and their verbal descriptions of a pattern were well correlated.

The role of oral methotrexate as a steroid sparing agent in refractory eosinophilic asthma.

The use of oral methotrexate for refractory eosinophilic asthma in a tertiary asthma referral centre, Glenfield Hospital, Leicester, was evaluated between January 2006 and December 2014. The patients ( n = 61) were carefully phenotyped at baseline with markers of airway inflammation. In addition, a structured oral methotrexate proforma was utilized to evaluate response to therapy and adverse events. Oral steroid withdrawal was attempted 3 months after commencing treatment. Several outcomes were evaluated at 12 months, including both efficacy and adverse effects; 15% ( n = 9/61) responded by achieving a decrease in daily oral corticosteroid dose (mean 8.43 (±8.76) mg), although we were unable to identify factors that predicted a treatment response. There were no other significant changes in any other clinical outcome measures. There was a high rate of adverse events (19/61 (31%)), primarily gastrointestinal/hepatitis. Our findings support the use of biological agents in preference to using oral methotrexate as a steroid sparing agent at the first instance. In the event of failure of these agents, oral methotrexate remains a therapeutic option, which can be considered in highly specialist severe asthma centres.

Controlled lateral anisotropy in correlated manganite heterostructures by interface-engineered oxygen octahedral coupling.

Controlled in-plane rotation of the magnetic easy axis in manganite heterostructures by tailoring the interface oxygen network could allow the development of correlated oxide-based magnetic tunnelling junctions with non-collinear magnetization, with possible practical applications as miniaturized high-switching-speed magnetic random access memory (MRAM) devices. Here, we demonstrate how to manipulate magnetic and electronic anisotropic properties in manganite heterostructures by engineering the oxygen network on the unit-cell level. The strong oxygen octahedral coupling is found to transfer the octahedral rotation, present in the NdGaO3 (NGO) substrate, to the La2/3Sr1/3MnO3 (LSMO) film in the interface region. This causes an unexpected realignment of the magnetic easy axis along the short axis of the LSMO unit cell as well as the presence of a giant anisotropic transport in these ultrathin LSMO films. As a result we possess control of the lateral magnetic and electronic anisotropies by atomic-scale design of the oxygen octahedral rotation.

Early definitive treatment rate as a quality indicator of care in acute gallstone pancreatitis.

BACKGROUND: Early definitive treatment (cholecystectomy or endoscopic sphincterotomy in the same admission or within 2 weeks after discharge) of gallstone disease after a biliary attack of acute pancreatitis is standard of care. This study investigated whether compliance with early definitive treatment for acute gallstone pancreatitis can be used as a care quality indicator for the condition. METHODS: A retrospective cohort study was conducted using the Hospital Episode Statistics database. All emergency admissions to National Health Service hospitals in England with a first time diagnosis of acute gallstone pancreatitis in the financial years 2008, 2009 and 2010 were examined. Trends in early definitive treatment between hospital trusts were examined and patient morbidity outcomes were determined. RESULTS: During the study interval there were 19 510 patients with an overall rate of early definitive treatment at 34·7 (range 9·4-84·7) per cent. In the 1-year follow-up period, 4661 patients (23·9 per cent) had one or more emergency readmissions for complications related to gallstone pancreatitis. Of these, 2692 (57·8 per cent) were readmissions for acute pancreatitis; 911 (33·8 per cent) were within the first 2 weeks of discharge, with the remaining 1781 (66·2 per cent) occurring after the point at which definitive treatment should have been received. Early definitive treatment resulted in a 39 per cent reduction in readmission risk (adjusted risk ratio (RR) 0·61, 95 per cent c.i. 0·58 to 0·65). The risk was further reduced for acute pancreatitis readmissions to 54 per cent in the early definitive treatment group (adjusted RR 0·46, 0·42 to 0·51). CONCLUSION: In acute gallstone pancreatitis, compliance with recommended early definitive treatment varied considerably, with associated variation in outcomes. Compliance should be used as a quality indicator to improve care.

Transition from Reconstruction toward Thin Film on the (110) Surface of Strontium Titanate.

The surfaces of metal oxides often are reconstructed with a geometry and composition that is considerably different from a simple termination of the bulk. Such structures can also be viewed as ultrathin films, epitaxed on a substrate. Here, the reconstructions of the SrTiO3 (110) surface are studied combining scanning tunneling microscopy (STM), transmission electron diffraction, and X-ray absorption spectroscopy (XAS), and analyzed with density functional theory calculations. Whereas SrTiO3 (110) invariably terminates with an overlayer of titania, with increasing density its structure switches from n × 1 to 2 × n. At the same time the coordination of the Ti atoms changes from a network of corner-sharing tetrahedra to a double layer of edge-shared octahedra with bridging units of octahedrally coordinated strontium. This transition from the n × 1 to 2 × n reconstructions is a transition from a pseudomorphically stabilized tetrahedral network toward an octahedral titania thin film with stress-relief from octahedral strontia units at the surface.

Mucosal and lacrimal flaps for endonasal dacryocystorhinostomy: a systematic review.

BACKGROUND: Historically dacryocystorhinostomy (DCR) has been performed externally with very good outcomes. Current literature shows comparable success rates between endonasal and external approaches. A common reason for the failure of a DCR is the reclosure of the nasolacrimal stoma by granulation tissue and synechiae. OBJECTIVE OF REVIEW: A systematic review and critical evaluation of the evidence relating to the preservation of nasal mucosal flaps in DCR surgery. TYPE OF REVIEW AND EVALUATION METHOD: A systematic review using the consort guidance for review of randomised control trials. SEARCH STRATEGY: A search of the following evidence-based medicine databases was performed: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials, Ovid, Medline, EMBASE and PubMed. The search was limited to English language articles, and the following key words were used: Endonasal, Endoscopic, Dacryocystorhinostomy, DCR, Mucosal Flaps, between years 1970 and 2015. RESULTS: The best available evidence was level 1B, comprising two randomised control trials and three comparative studies included in the review. The main outcome measures used were lacrimal irrigation and absence of epiphora. Two of the studies demonstrated a statistically significant benefit of mucosal sparing either with nasal mucosal flaps or with lacrimal flaps. More debridement was needed, and granulation tissue was also seen in the groups without mucosal preservation. There was no difference in surgical complications between a mucosal and non-mucosal-sparing technique. CONCLUSIONS: The overall quality of current evidence is poor, and there does however appear to be a trend towards improved outcomes and reduced granulation in groups where nasal mucosal and lacrimal flaps were preserved, but this is not clear-cut. There was no evidence of increased complication rates with mucosal-sparing techniques. We recommend that until further good quality research is available we should be performing a mucosal-sparing technique when performing DCR routinely.

Extreme mobility enhancement of two-dimensional electron gases at oxide interfaces by charge-transfer-induced modulation doping.

Two-dimensional electron gases (2DEGs) formed at the interface of insulating complex oxides promise the development of all-oxide electronic devices. These 2DEGs involve many-body interactions that give rise to a variety of physical phenomena such as superconductivity, magnetism, tunable metal-insulator transitions and phase separation. Increasing the mobility of the 2DEG, however, remains a major challenge. Here, we show that the electron mobility is enhanced by more than two orders of magnitude by inserting a single-unit-cell insulating layer of polar La(1-x)Sr(x)MnO3 (x = 0, 1/8, and 1/3) at the interface between disordered LaAlO3 and crystalline SrTiO3 produced at room temperature. Resonant X-ray spectroscopy and transmission electron microscopy show that the manganite layer undergoes unambiguous electronic reconstruction, leading to modulation doping of such atomically engineered complex oxide heterointerfaces. At low temperatures, the modulation-doped 2DEG exhibits Shubnikov-de Haas oscillations and fingerprints of the quantum Hall effect, demonstrating unprecedented high mobility and low electron density.

Hip abductor muscle volume in hip osteoarthritis and matched controls.

OBJECTIVE: Hip abductor muscle strength and function is negatively impacted by the presence of hip osteoarthritis (OA). This study aimed to quantify differences in hip abductor muscle volume, fatty infiltration and strength in a unilateral hip OA population when compared to a control group. Impact of radiographic severity of OA on these variables was also examined. METHODS: Volumes of gluteus maximus (GMax), medius (GMed) minimus (GMin) and tensor fascia lata (TFL) was measured using MRI and muscle volume asymmetry between limbs was calculated. Fatty infiltrate within muscles was graded using the Goutallier classification system. Hip abduction and rotation strength was tested using a dynamometer. Differences between groups or limbs were analysed using t-tests and differences in fatty infiltration using non-parametric tests. RESULTS: A statistically significant decrease in muscle volume was identified in GMax (P < 0.01), GMed (P < 0.02) and GMin (P < 0.01) on the affected side in the OA group compared to both the contralateral side and the control group and differences were related to severity of OA. Hip abduction and internal rotation strength was reduced in the OA group. Increased levels of fatty infiltration were identified in the affected limbs of the OA group for GMax (P = 0.01) and GMin (P = 0.04). CONCLUSION: Gluteal muscle atrophy, increased gluteal fatty infiltration and hip strength deficits were evident in the affected hips of OA participants. Since severity of OA was related to the extent of atrophy and fatty deposits, rehabilitation programs targeting these muscles could reverse or halt the progression of these structural and functional deficits.

Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients.

OBJECTIVE: To identify novel biomarker(s) for knee osteoarthritis (OA) using a metabolomics approach. METHOD: We utilized a two-stage case-control study design. Plasma samples were collected from knee OA patients and healthy controls after 8-h fasting and metabolically profiled using a targeted metabolomics assay kit. Linear regression was used to identify novel metabolic markers for OA. Receiver operating characteristic (ROC) analysis was used to examine diagnostic values. Gene expression analysis was performed on human cartilage to explore the potential mechanism for the novel OA marker(s). RESULTS: Sixty-four knee OA patients and 45 controls were included in the discovery stage and 72 knee OA patients and 76 age and sex matched controls were included in the validation stage. We identified and confirmed six metabolites that were significantly associated with knee OA, of which arginine was the most significant metabolite (P < 3.5 × 10(-13)) with knee OA patients having on average 69 µM lower than that in controls. ROC analysis showed that arginine had the greatest diagnostic value with area under the curve (AUC) of 0.984. The optimal cutoff of arginine concentration was 57 µM with 98.3% sensitivity and 89% specificity. The depletion of arginine in OA patients was most likely due to the over activity of arginine to ornithine pathway, leading to imbalance between cartilage repair and degradation. CONCLUSION: Arginine is significantly depleted in refractory knee OA patients. Further studies within a longitudinal setting are required to examine whether arginine can predict early OA changes.