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Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM,' had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM.' A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as 'possible IIM.' Conclusion The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite,' 'probable,' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria. [ABSTRACT FROM AUTHOR]

Patients with end-stage renal disease (ESRD) are at increased risk for Hepatitis B virus (HBV) exposure and subsequent infection. Waning immunity, despite strong initial vaccination efforts, is increasingly common and leads to serial testing and repeated vaccination efforts. In partnership with our colleagues in hemodialysis (HD), we sought to develop comprehensive, screening, testing, clinical, and infection prevention and control (IPC) guidelines for HBV in the inpatient hemodialysis unit. We performed a detailed literature review using Medline and PubMed with specific key words regarding HBV exposure, vaccination, infection prevention and clinical testing guidance. Using the Delphi method and an iterative review process, we developed an algorithm that was reviewed and refined with hemodialysis staff, nephrologists, the IPC team and clinical infectious disease experts. All possible combinations of HBV test results were reviewed and then paired with testing interpretation guidance, immediate clinical steps, and IPC guidance. Implementation of the tool resulted in improved communication between the HD unit and IPC team around isolation precaution needs, physical placement of the patient and dialysis machine disinfection. However, we also identified several gaps including a lack of closed-loop communication between outpatient HD facilities and our inpatient dialysis unit, difficulty in screening for HBV re-activation risk, lack of standard guidance regarding the frequency of screening leading to confusion for IPC and HD staff, and difficulty in discharge communication with outpatient dialysis facilities. The use of a standardized evidence-based algorithm improved adherence to HBV screening, vaccination, as well as machine disinfection and isolation practices. However, additional areas for improvement were identified through the implementation process. Future interdisciplinary guidance should address screening ambiguities and how that may lead to mixed IPC practices in both inpatient and outpatient HD settings. [ABSTRACT FROM AUTHOR]

Hand hygiene (HH) is a critical part of Infection Prevention and one of the most difficult interventions to measure. In 2021, a reputational organization required a significant increase with up to 200 HH observations per unit per month. Without electronic HH monitoring in place, our large academic medical center had to upscale our existing program quickly to comply. The HH program at our institution used a 'secret shopper' direct observation, with observations collected by part-time employees using a real-time REDCap data entry form, with no limit on number of opportunities observed and collected during a single session. Multiple additional HH observers were hired and trained rapidly to support increased observation volume. An additional REDCap tool was added to more accurately capture observations in procedural and ambulatory care areas. Data is extracted daily using an Application Programming Interface (API) from REDCap, from which we built a hospital dashboard in Microsoft PowerBI. Our hospital-wide HH dashboard is universally accessible, and displays the percent compliance institution-wide and by unit. The interactive dashboard shows the number of observations by unit and percent compliance by type of healthcare provider and type of HH opportunity. This allowed the Infection Control team to create real time, institutional awareness for HH compliance, allowing for targeted interventions and helped achieve 200 observations per month. The ease of use and ability to purpose-build the REDCap tool enabled expansion of the HH program into ambulatory care areas with additional trained ambulatory observers. This cost-effective approach allows us to scale up or down our HH program without capital expenditures nor physical modifications to the institution. Our data visualization dashboard is a simple intervention that provides real time data for hospital employees and leadership to emphasize the importance of HH, as well as assists Infection Control in tracking HH compliance and opportunities. [ABSTRACT FROM AUTHOR]

Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. [ABSTRACT FROM AUTHOR]

Isolated congenital complete heart block (CCHB) is a rare disease with significant associated morbidity and mortality. A diagnosis is often made in fetal life, but data regarding long-term outcomes are limited, and fetal therapy to improve prognosis is controversial. In our institution, 85 fetuses were diagnosed with CCHB from 1981 to 2013 in 80 mothers. There were 37 anti-Ro-positive pregnancies, 36 both anti-Ro and anti-La positive, 10 antibody negative, and 2 of unknown antibody status. Antenatal treatments were given in 14 fetuses, with 8 given fluorinated steroids, 4 beta sympathomimetics, and both in 2. Of the original 85, 74 babies survived to delivery. Fetal hydrops was the only risk factor found to be significantly associated with intrauterine death (p <0.001). Four babies died before pacemaker implantation, 56 have had pacemakers implanted, and 14 are pacemaker free. The Kaplan-Meier estimate for median time to pacemaker implantation was 2.6 years, with 15 implanted in the neonatal period. There have been 14 postnatal deaths, with a Kaplan-Meier estimate of survival at 30 years of 76.8% (95% confidence interval 65% to 90%). Dilated cardiomyopathy was uncommon, occurring in 6 patients. Prematurity and hydrops were associated with increased postnatal mortality (p = 0.02 and 0.005, respectively). In conclusion, we present the largest single-unit experience of prenatally diagnosed CCHB in the published literature. Our cohort was conservatively managed, with survival similar to those previously published. These data offer insight into the long-term natural history of CCHB. [ABSTRACT FROM AUTHOR]

Introduction: We investigated whether muscle endurance differs between IIM patients and controls and if a relationship exists between perceived fatigue and poor muscle endurance. Methods: Quadriceps contractility, measured using femoral nerve stimulation (TwQ), and strength, measured using maximal voluntary contraction (MVCQ), were assessed in 20 IIM patients and matched controls. Quadriceps endurance was assessed using repetitive electrical stimulation (3 minutes). Time for force to fall to 70% initial force was determined (T70). Reported fatigue was measured using the FACIT-F/Fatigue Severity Scales. Results: TwQ and MVCQ were lower and perceived fatigue greater for patients. There was no difference in T70 between groups. No relationships were observed between perceived fatigue and endurance (T70). Conclusions: IIM patients reported more fatigue and were weaker than controls, but there was no difference in muscle endurance. Endurance and strength were unrelated to reported fatigue measures. Mechanisms driving perceived IIM fatigue are likely to be multifactorial. [ABSTRACT FROM AUTHOR]

The LIM-Homeodomain transcription factor Lhx2 is an essential organizer of early eye development and is subsequently expressed in retinal progenitor cells (RPCs). To determine its requirement in RPCs, we performed a temporal series of conditional inactivations in mice with the early RPC driver Pax6 a-Cre and the tamoxifen-inducible HeslCreERI2 driver. Deletion of Lhx2 caused a significant reduction of the progenitor population and a corresponding increase in neurogenesis. Precursor fate choice correlated with the time of inactivation; early and late inactivation led to the overproduction of retinal ganglion cells (RGCs) and rod photoreceptors, respectively. In each case, however, the overproduction was selective, occurring at the expense of other cell types and indicating a role for Lhx2 in generating cell type diversity. RPCs that persisted in the absence oiLhx2 continued to generate RGC precursors beyond their normal production window, suggesting that Lhx2 facilitates a transition in competence state. These results identify Lhx2 as a key regulator of RPC properties that contribute to the ordered production of multiple cell types during retinal tissue formation. [ABSTRACT FROM AUTHOR]

Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an 'individual funding request', the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA. [ABSTRACT FROM AUTHOR]

The enzyme-based cleaning of two model protein soils was investigated using a scanning fluid dynamic gauge (sFDG). The sFDG device allows data to be collected from more than one sample or location during a single experiment and therefore makes a range of comparative studies feasible. The sFDG was modified to allow the forces imposed on the surface to be controlled during a test. Gelatine films on stainless steel swelled in the presence of alkali at 20 °C but were not removed. Enzymes from a commercial dishwasher product interrupted swelling when the mean water volume fraction of the film reached ~0.9 and promoted removal. The enzyme effectiveness decreased over time. Egg yolk deposits (spray dried on mica) were studied in a protease/buffer solution at 40 °C. The deposits swelled on contact with alkali, and removal started after ~40 min. Some flow over the deposit was required to achieve complete cleaning, but the time taken to clean exhibited a weak dependence on the shear stress imposed by the flow for shear stresses above 10 Pa. The cleaning behaviour was strongly influenced by the nature of the deposit. Baking the deposit at 150 °C reduced the rate and extent of swelling as well as the rate of removal, and could result in the formation of a residual film that exhibited yield stress characteristics. [ABSTRACT FROM AUTHOR]

Fluid dynamic gauging (FDG) has been developed to measure both the thickness and strength (cohesive or adhesive) of a range of fouling deposits, in situ and in real time. We report the development of a scanning FDG device (sFDG) with fully automated movement and deposit thickness measurement. Thickness-time profiles can be collected for several points on the surface over the course of a single experiment. sFDG is employed here to study the cleaning kinetics of model gelatine fouling layers when contacted with aqueous solutions at different pHs and temperatures, and with a commercial dishwasher formulation containing enzymes. Solution pH is an important parameter: above ∼pH 10.6 the gelatine layers swell markedly, due to protonation of the amino acids proline and hydroxyproline, and subsequent charge repulsion within the gel. An unusual behaviour (discontinuity) is reported during swelling in the commercial formulation. It is proposed that hydration of the deposit and an extent of swelling (ratio of the final to the initial deposit thickness) of ∼12 is necessary before the enzymes can promote deposit removal. [ABSTRACT FROM AUTHOR]