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Eosinophilic oesophagitis (EoE) is a rare, chronic, relapsing immune/antigen-mediated disease characterised by symptoms of oesophageal dysfunction, with a paucity of data among New Zealand (NZ) children. This 3-year prospective study aimed to characterise EoE diagnosed nationally and to describe initial treatment strategies adopted.

Information on new diagnoses of paediatric EoE was obtained via the New Zealand Paediatric Surveillance Unit, through monthly questionnaires.

From February 2014 to January 2017, 73 new cases (74% male) of EoE were reported, including 74% NZ European, 10% Asian, 7% Māori, 5% Middle-Eastern and 3% Pacific peoples. Median age of symptom onset was 4 years; dysphagia (48%) was the most common, followed by vomiting/regurgitation (40%), food impaction (19%) and epigastric pain (16%). A co-morbid history of other allergic conditions was present in 62% of patients, and 41% had a first degree relative with atopy. Seventy-nine percent of patients had abnormal endoscopic findings, most improve our knowledge of this rare condition.Nutrient pollution is altering coastal ecosystems worldwide. On coral reefs, excess nutrients can favor the production of algae at the expense of reef-building corals, yet the role of nutrients in driving community changes such as shifts from coral to macroalgae is not well understood. Here we investigate the potential role of anthropogenic nutrient loading in driving recent coral-to-macroalgae phase shifts on reefs in the lagoons surrounding the Pacific island of Moorea, French Polynesia. We use nitrogen (N) tissue content and stable isotopes (δ15 N) in an abundant macroalga (Turbinaria ornata) together with empirical models of nutrient discharge to describe spatial and temporal patterns of nutrient enrichment in the lagoons. We then employ time series data to test whether recent increases in macroalgae are associated with nutrients. Our results revealed that patterns of N enrichment were linked to several factors, including rainfall, wave-driven circulation, and distance from anthropogenic nutrient sources,ystems.

To investigate latent patterns of alcohol use and bingeing by gender and their association with depressive symptom severity and individual depressive symptoms.

Cross-sectional data were collected from January 2017 to March 2018 as part of a joint screening recruiting for different intervention studies.

Ambulatory practices and general hospitals from three sites in Germany.

A total of 5208 male and 5469 female proactively recruited alcohol users aged 18-64years.

Frequency and typical quantity of alcohol use, frequency of bingeing, alcohol-related problems (assessed by the Alcohol Use Disorder Identification Test); depressive symptom severity, individual depressive symptoms (assessed with the Patient Health Questionnaire-8); and socio-demographics and health-related variables.

Latent categorical analysis identified six patterns of alcohol use, with the majority of patients engaging in 'light use plus no or occasional bingeing' (males 41.85%; females 64.04%), followed by 'regular use plus occasional r guilt and psychomotor agitation or retardation, being especially pronounced in the 'frequent use plus frequent bingeing' class (RRRs

=1.72-2.36; RRRs

=1.99-2.17).

Patterns of 'frequent alcohol use plus frequent bingeing' and 'occasional alcohol use plus occasional bingeing' appear to have positive associations with depression when compared with 'light alcohol use plus no or occasional bingeing'.

Patterns of 'frequent alcohol use plus frequent bingeing' and 'occasional alcohol use plus occasional bingeing' appear to have positive associations with depression when compared with 'light alcohol use plus no or occasional bingeing'.The localizationist model, which focused on classical cortical areas such as Broca's and Wernicke's, can no longer explain how language processing works. Over recent years, several studies have revealed new language-related cortical and subcortical areas, resulting in a transition from localizationist concepts to a hodotopical model. These studies have described language processing as an extensive and complex network of multiple interconnected cortical areas and subcortical pathways, differing from the classical circuit described by the localizationist perspective. The hodotopical model was made possible by a paradigm shift in the treatment of cerebral tumors, especially low-grade gliomas total or subtotal tumor resections with cortical and subcortical mapping on awake patients have become the gold standard treatment for lesions located in the dominant hemisphere. In this article, we review current understating of the microsurgical anatomy of language.In recent years, antimicrobial-resistant Pseudomonas aeruginosa strains have increased in the veterinary field. Therefore, phage therapy has received significant attention as an approach for overcoming antimicrobial resistance. In this context, we isolated and characterized four Pseudomonas bacteriophages. Phylogenetic analysis showed that the isolated phages are novel Myoviridae Pbunavirus PB1-like phages with ØR12 belonging to a different clade compared with the other three. These phages had distinct lytic activity against 22 P. aeruginosa veterinary isolates. The phage cocktail composed from the PB1-like phages clearly inhibited the occurrence of the phage-resistant variant, suggesting that these phages could be useful in phage therapy.All accounts of language acquisition agree that, by around age 4, children's knowledge of grammatical constructions is abstract, rather than tied solely to individual lexical items. The aim of the present research was to investigate, focusing on the passive, whether children's and adults' performance is additionally semantically constrained, varying according to the distance between the semantics of the verb and those of the construction. In a forced-choice pointing study (Experiment 1), both 4- to 6-year olds (N = 60) and adults (N = 60) showed support for the prediction of this semantic construction prototype account of an interaction such that the observed disadvantage for passives as compared to actives (i.e., fewer correct points/longer reaction time) was greater for experiencer-theme verbs than for agent-patient and theme-experiencer verbs (e.g., Bob was seen/hit/frightened by Wendy). Similarly, in a production/priming study (Experiment 2), both 4- to 6-year olds (N = 60) and adults (N = 60) produced fewer passives for experiencer-theme verbs than for agent-patient/theme-experiencer verbs. We conclude that these findings are difficult to explain under accounts based on the notion of A(rgument) movement or of a monostratal, semantics-free, level of syntax, and instead necessitate some form of semantic construction prototype account.

This study investigated the impact of a transdisciplinary advanced allied health practitioner (AAHP) in a public hospital general paediatric outpatient department for children referred for concerns with neurodevelopment, learning and/or behaviour. It was hypothesised that time from referral to initial consultation and diagnosis was reduced for children initially assessed by AAHP. It was also hypothesised that children seen by AAHP were less likely to require a medical specialist appointment.

De-identifiable data were gathered from hospital records both retrospectively and prospectively for each group. Data were collected from 75 children who attended a medical consultation only clinic in 2014; 75 children who attended an AAHP clinic and a medical officer in 2014 and 75 children who attended an AAHP clinic and a medical officer 2 years after establishment in 2016/2017.

On average, 52% children were managed independently by the AAHP. Wait time from referral to consultation significantly decreased from 169 days to 48 days. Similarly, time from referral to diagnosis significantly reduced by almost a half, from 57.2 to 30.59 weeks.

This study provides preliminary evidence that utilisation of transdisciplinary AAHPs in general paediatric outpatient departments may reduce waitlists, reduce amount of medical specialist appointments required and provide earlier diagnosis for children with neurodevelopmental, behavioural and/or learning difficulties.

This study provides preliminary evidence that utilisation of transdisciplinary AAHPs in general paediatric outpatient departments may reduce waitlists, reduce amount of medical specialist appointments required and provide earlier diagnosis for children with neurodevelopmental, behavioural and/or learning difficulties.Arachidonic acid 15-lipoxygenases (ALOX15) are lipid peroxidizing enzymes, which has previously been implicated in the maturational breakdown of intracellular organelles and plasma membrane remodeling during reticulocyte-erythrocyte transition. Conventional Alox15-/- mice are viable, develop normally but do not exhibit a major defective erythropoietic phenotype. To characterize the putative in vivo relevance of Alox15 for red blood cell development, we explored the impact of systemic inactivation of the Alox15 gene on mouse erythropoiesis. We found that Alox15-/- mice exhibited reduced erythrocyte counts, elevated reticulocyte counts and red cell hyperchromia. The structure of the plasma membrane of Alox15-/- erythrocytes is altered and a significant share of the red cells was present as echinocytes and/or acanthocytes. An increased share of the Alox15-/- erythrocytes cells were annexin V positive, which indicates a loss of plasma membrane asymmetry. Erythrocytes of Alox15-/- mice were more susceptible to osmotic hemolysis and exhibited a reduced ex vivo life span. When we transgenically expressed human ALOX15 in Alox15-/- mice under the control of the aP2 promoter the defective erythropoietic system was rescued and the impaired osmotic resistance was normalized. Together these data suggest the involvement Alox15 in the maturational remodeling of the plasma membrane during red cell development.The brown dog tick, Rhipicephalus sanguineus sensu lato (s.l.) Latreille (Acari Ixodidae), is a peridomestic, cosmopolitan parasite of dogs known to vector numerous pathogens of veterinary and medical importance. Recent phylogenetic analyses separate this tick into temperate and tropical lineages. Populations of Rh. sanguineus s.l. have been reported to exhibit sodium channel target site insensitivity to permethrin and etofenprox, which is likely due to the prolonged use of pyrethroids against many pests in and around the home. In this study, populations collected in the Caribbean, Africa, Asia, Europe and North America, were tested to identify the distribution of a known resistance mechanism, pathogen-vector interactions and phylogeny in relation to latitude. Using molecular assays, populations from 29 distinct locations were simultaneously geographically typed and screened for bacterial infection by Rickettsia, Ehrlichia, Babesia and Hepatozoon species, and for the presence of a sodium channel single nucleotide polymorphism known to confer permethrin resistance. Implications of these results on Rh. sanguineus s.l. management in association with geographical distribution will be discussed.

Patients with Gaucher disease (GD) have an increased risk for parkinsonism. Retinal thinning has been described in parkinsonism as an early nonmotor feature. Scarce reports have addressed retinal thickness changes in GD.

The objectives of this study were to compare ganglion cell complex (GCC) thickness in adolescents and young adults (AYAs) with GD with healthy control subjects, and to correlate it with the presence of parkinsonian features (PFs), clinical prodromal markers of parkinsonism, severity score index (SSI), and glucosylsphingosine (Lyso-GL-1).

This study included 48 AYAs with GD (11-29 years), 11 with manifest PFs (Group 1) and 37 with no PFs (Group 2), and 48 matched healthy control subjects (Group 3). Age of GD onset, disease duration, medication history, history of constipation, SSI, and hematological assessment were done. Neurocognitive evaluation included Parts I, II, and III of the Unified Parkinson's Disease Rating Scale (UPDRS), Wechsler Adult and Intelligence Scale and Wechsler Intel), RBD (P = 0.044), and hyposmia (P = 0.033).

GCC thinning may be a promising biomarker for central nervous system neurodegeneration that has the potential to monitor early PFs among people with GD. © 2020 International Parkinson and Movement Disorder Society.

GCC thinning may be a promising biomarker for central nervous system neurodegeneration that has the potential to monitor early PFs among people with GD. © 2020 International Parkinson and Movement Disorder Society.Mycoplasma pneumoniae-induced rash and mucositis is the most accurate diagnosis for patients with blistering mucocutaneous disease provoked by an infection. Recent literature suggests expansion of the name is required, as other infections have caused a clinically similar presentation. This review provides a concise update on current understanding of M. pneumoniae-induced rash and mucositis and other reactive infectious mucocutaneous eruptions.

Early diagnosis is very important to improve the survival rate of patients with gastric cancer (GC), especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of GC. In this study, we explored whether MIC-1 can improve the detection rate of early GC.

We screened 8257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4, and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4, and PG1/PG2, and its role in early GC diagnosis and the assessment of the risk of precancerous lesions have also been studied.

Based on endoscopic and histopathological findings, 55 participants had GC, 566 participants had low-grade neoplasia, and 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in GC serum samples as compared to controls (P<.001). The sensitivity of serum MIC-1 for GC diagnosis was much higher than that of CA-199 (49.1% vs 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4, and PG1/PG2 in distinguishing early-stage GC (AUC 72.9% vs 69.5%, 67.5%, 44.0%, respectively).

Serum MIC-1 is significantly elevated in most patients with early GC. MIC-1 can serve as a novel diagnostic marker of early GC and value the risk of GC.

Serum MIC-1 is significantly elevated in most patients with early GC. MIC-1 can serve as a novel diagnostic marker of early GC and value the risk of GC.

With the outbreak of coronavirus disease 2019 (COVID-19), clinicians have used personal protective equipment to avoid transmission of severe acute respiratory syndrome coronavirus2. However, they still face occupational risk of infection, when treating COVID-19 patients. This may be highest during invasive diagnostic procedures releasing aerosols and droplets. Thereby, the use of diagnostic procedures for Covid-19 associated aspergillosis may be delayed or impeded, as use of bronchoscopy has been discouraged. This leads to avoidance of a crucial procedure for diagnosing invasive aspergillosis. We intent to visualise aerosol and droplet spread and surface contamination during bronchoscopy and address which measures can avoid exposure of health-care workers.

We created a simulation model to visualise aerosol and droplet generation as well as surface contamination by nebulising fluorescent solution detected by using ultraviolet light- and slow-motion capture. We repurposed covers for ultrasound transducers or endoscopic cameras to prevent surface and ambient air contamination.

In our bronchoscopy simulation model, we noticed extensive aerosol generation, droplet spread and surface contamination. Exposure of health-care workers and contamination of surfaces can be efficiently reduced by repurposing covers for ultrasound transducers or endoscopic cameras to seal the tube opening during bronchoscopy in mechanically ventilated patients.

Adequate personal protective equipment and safety strategies allow to minimise contamination during bronchoscopy in mechanically ventilated COVID-19 patients.

Adequate personal protective equipment and safety strategies allow to minimise contamination during bronchoscopy in mechanically ventilated COVID-19 patients.Adult T-cell leukemia (ATL) is a life-threatening malignant neoplasm of CD4+ T cells resulted from human T-cell leukemia virus type I (HTLV-I). Tax1 protein of HTLV-I can induce malignant proliferation of T-cells by modulating the expression of growth factors such as platelet-derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV-I in ATL and also to evaluate the mRNA expression of B chain of PDGF and PDGF-β receptors in ATL patients and HTLV-I-infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll-Histophaque density centrifugation. The mean of HTLV-I PVL in ATL patients (42,759 ± 15,737 copies/104 cells [95% CI, 9557-75962]) was significantly (p = .01) higher than that in healthy carriers (650 ± 107 copies/104 cells [95% CI, 422-879], respectively. The HTLV-I PVL in ATL patients exhibited a significant correlation with PBMC count (R = .495, p = .001). The mRNA expression of Tax, B chain of PDGF, and PDGF-β receptor genes was significantly higher in healthy carriers than in patients with ATL. In conclusion, the expression of the canonical PDGFβ and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV-I carriers.

Parotid lymph node metastases are common in head and neck cutaneous squamous cell carcinoma (cSCCHN). Here we evaluate the diagnostic, prognostic, and therapeutic implications of intraglandular lymph node (IGLN) metastases in cSCCHN.

Retrospective study in a tertiary referral university cancer institute.

We included patients with cSCCHN who underwent parotidectomy and neck dissection (ND), with or without synchronous resection of the skin primary, between January 1999 and January 2018. The characteristics of cSCCHN with or without IGLN involvement were compared.

Altogether, 68 patients were included. Of the 29 (42.6%) patients classified as cN0, eight were upstaged pN+ and had concomitant IGLN involvement. Of 21 patients with pN0 disease, IGLN metastases were absent in only three cases, resulting in a specificity and sensitivity of parotid metastases to diagnose occult nodal neck metastases of 14.29% and 100%, respectively. The positive and negative predictive values were 14.29% and 100%, respectively. Univariate analyses only displayed a significantly higher rate of moderately and poorly differentiated primaries in patients with IGLN metastases (P = .015). Only advanced T-stages were significantly associated with neck recurrences.

IGLN status in advanced cSCCHN is potentially predictive for occul nodal neck metastases. Our results suggest that ND in patients with histopathologically negative IGLNs and clinically negative neck lymph nodes may not be necessary given the high negative predictive value of IGLN status in this group of patients. Therefore, accurate diagnostic evaluation of IGLN involvement is mandatory.

4 Laryngoscope, 2020.

4 Laryngoscope, 2020.Abiotrophia defectiva is a species of nutritionally variant streptococci that is found in human saliva and dental plaques and that has been associated with infective endocarditis. In our previous study, it was found that A. defectiva could bind specifically to saliva-coated hydroxyapatite beads (SHA). This study identified a cell surface component of A. defectiva that promotes adherence to SHA beads. The binding of A. defectiva to SHA was reduced in the presence of antibodies against human proline-rich protein (PRP); these results suggested that PRP may be a critical component mediating interactions between A. defectiva and the salivary pellicle. Two-dimensional gel electrophoresis of whole A. defectiva cells followed by Far-Western blotting was conducted by probing with synthetic peptides analogous to the binding region of PRP known as PRP-C. The results indicate that an A. defectiva protein of 37 kDa interacts with PRP-C. The results of amino-terminal sequencing of the adhesive A. defectiva protein revealed significant similarity to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Recombinant GAPDH bound to immobilized PRP-C in a dose-dependent manner and binding of A. defectiva to SHA or to PRP was reduced in the presence of anti-GAPDH antiserum. Western blotting or electron immunomicroscopic observations with anti-GAPDH antiserum revealed that this protein was expressed in both cytosolic and cell wall fractions. These results suggest that A. defectiva could specifically bind to PRP via interactions with cell surface GAPDH; the findings suggest a mechanism underlying A. defectiva-mediated adherence to saliva-coated tooth surfaces.Total ankle arthroplasty (TAA) is a common surgical approach for patients with end-stage ankle osteoarthritis (OA). However, very little is known about the path of the center of pressure (COP) of the foot, and thus important aspects of load transfer, muscle mechanical advantage, and balance, in patients before or after surgery. The objective of this study was to trace the pathway of the COP under the foot in patients with symptomatic ankle OA, comparing asymmetry between affected and unaffected limbs. From force plate data, proximodistal and mediolateral positions of the COP beneath the foot were calculated and compared for the affected and unaffected foot in patients with unilateral ankle OA (N = 93) before and after TAA. Gender and age at surgery had little or no effect in this study. Patients with ankle OA had minimal COP position asymmetry before surgery, and this asymmetry was reduced following surgery. Before surgery, patients had a slower walking speed and a shorter path of the COP which began relatively distal to the heel and ended relatively proximal to the hallux. TAA increased the proximodistal distance the COP traveled under both the unaffected and affected foot, a pattern that was maintained for over 2-year postsurgery. TAA allows patients with ankle OA to maintain a longer COP path than they had before surgery on both sides that is closer to that reported for unaffected individuals, extending effectively from the heel to the hallux, potentially improving pedal mechanics.Physical activity is important for physical function and pain relief in people with lower extremity osteoarthritis (OA). Unfortunately, people with OA are not as active as their peers without OA. The objective of this study was to determine whether aerobic capacity and fatigability are associated with physical activity in women with hip OA. We conducted a cross-sectional analysis of 36 women with hip OA. We assessed aerobic fitness as predicted VO2 max from a 6-min walk test. We assessed fatigability using a treadmill test. Finally, we assessed self-reported physical activity using the UCLA activity scale and quantified steps per day and activity intensity using accelerometers. We used Pearson correlations to determine associations. We used regression analysis to determine whether fatigability mediated the association between aerobic fitness and physical activity. On average, subjects were moderately active via the UCLA score (5.2 ± 1.3 out of 10). Aerobic fitness (R = 0.582, p  less then  .001) and fatigability (R = 0.516, p =.003) were significantly correlated with UCLA scores. However, aerobic fitness was the best predictor of UCLA scores, as well as sedentary time, and time spent in light activity. Fatigability was not a mediator between aerobic fitness and UCLA scores. Aerobic fitness and fatigability may be modifiable barriers to physical activity in people with OA. Future interventional studies should examine whether improving aerobic fitness improves physical activity or fatigability.Nickel (Ni) and glyphosate (Gl) are able to reduce the symptoms of Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, in soybean. However, their combined effects on the energy balance and ethylene metabolism of soybean plants infected with this fungus has not been elucidated. Therefore, the effects of Ni, Gl, and the combination of Ni + Gl on ASR development, photosynthetic capacity, sugar concentrations, and ethylene concentrations in plants of a Gl-resistant cultivar, uninfected or infected with P. pachyrhizi, were investigated. Inoculated plants supplied with Ni had the highest foliar Ni concentration in all the treatments. Gl had a negative effect on the foliar Ni concentration in Ni-sprayed plants. The ASR severity was reduced in plants sprayed with Ni and Gl. Carotenoid and chlorophyll concentrations were higher in inoculated Ni, Gl, and Ni + Gl plants than in control plants. Based on the chlorophyll a fluorescence parameters, the photosynthetic apparatus of the control inoculated plants was damc capacity during the P. pachyrhizi infection process; as a result, these plants consumed less of their reserves than inoculated plants not treated with Ni or Gl.One central task in precision medicine is to establish individualized treatment rules (ITRs) for patients with heterogeneous responses to different therapies. Motivated from a randomized clinical trial for Type 2 diabetic patients on a comparison of two drugs, that is, pioglitazone and gliclazide, we consider a problem utilizing promising candidate biomarkers to improve an existing ITR. This calls for a biomarker evaluation procedure that enables to gauge added values of individual biomarkers. We propose an assessment analytic, termed as net benefit index (NBI), that quantifies a contrast between the resulting gain and loss of treatment benefits when a biomarker enters ITR to reallocate patients in treatments. We optimize reallocation schemes via outcome weighted learning (OWL), from which the optimal treatment group labels are generated by weighted support vector machine (SVM). To account for sampling uncertainty in assessing a biomarker, we propose an NBI-based test for a significant improvement over the existing ITR, where the empirical null distribution is constructed via the method of stratified permutation by treatment arms. Applying NBI to the motivating diabetes trial, we found that baseline fasting insulin is an important biomarker that leads to an improvement over an existing ITR based only on patient's baseline fasting plasma glucose (FPG), age, and body mass index (BMI) to reduce FPG over a period of 52 weeks.Compartmentalization is an essential feature of all cells. It allows cells to segregate and coordinate physiological functions in a controlled and ordered manner. Different mechanisms of compartmentalization exist, with the most relevant to prokaryotes being encapsulation via self-assembling protein-based compartments. One widespread example of such is that of encapsulins-cage-like protein nanocompartments able to compartmentalize specific reactions, pathways, and processes in bacteria and archaea. While still relatively nascent bioengineering tools, encapsulins exhibit many promising characteristics, including a number of defined compartment sizes ranging from 24 to 42 nm, straightforward expression, the ability to self-assemble via the Hong Kong 97-like fold, marked physical robustness, and internal and external handles primed for rational genetic and molecular manipulation. Moreover, encapsulins allow for facile and specific encapsulation of native or heterologous cargo proteins via naturally or rationally fused targeting peptide sequences. Taken together, the attributes of encapsulins promise substantial customizability and broad usability. This review discusses recent advances in employing engineered encapsulins across various fields, from their use as bionanoreactors to targeted delivery systems and beyond. A special focus will be provided on the rational engineering of encapsulin systems and their potential promise as biomolecular research tools.Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide. So, there is a need to identify AD early diagnosis and monitoring biomarkers in blood samples. The aim of this study was to analyse the utility of lipid peroxidation biomarkers in AD progression evaluation. Participants (n = 19) were diagnosed with AD at early stages (Time 0, T0), and they were re-evaluated 2 years later (Time 1, T1). Plasma biomarkers from AD patients were determined at both times. Some analytes, such as dihomo-isoprostanes (17-epi-17-F2t-dihomo-IsoP, 17-F2t-dihomo-IsoP, Ent-7(RS)-7-F2t-dihomo-IsoP), and neuroprostanes (10-epi-10-F4t-NeuroP) showed very high probability of showing an increasing trend over time. Baseline values allowed to develop an affordable preliminary regression model to predict long-term cognitive status. So, some lipid peroxidation biomarkers would deserve consideration as useful progression AD biomarkers. The developed prediction model would constitute an important minimally invasive approach in AD personalized prognosis and perhaps could have some interest also in experimental treatments evaluation.

Studies comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking.

Medical records of 76 adults with FR/SD MCD who were treated with corticosteroids as the first-line therapy were reviewed. Treatment options were compared for the time to relapse, change of therapy and progression (relapse on full-dose treatment).

Second-line treatments included rituximab (RTX; n = 13), mycophenolate mofetil (MMF; n = 12), calcineurin inhibitors (CNI; n = 26) and cyclophosphamide (CTX; n = 16). During the second-line treatments, 48 (71.6%) patients relapsed at median 17 (range 2-100)  months. The majority of relapses occurred during dose tapering or off drug. Twenty of 65 (30.8%) changed therapy after the first relapse. The median time to relapse after the second line was 66 versus 28 months in RTX versus non-RTX groups (P = 0.170). The median time to change of treatment was 66 and 44 months, respectively (P = 0.060). Last-line treatment options included RTX (n = 8), MMF (n = 4), CNI (n = 3) and CTX (n = 2). Seven (41.2%) patients had a relapse during the last-line treatment at median 39 (range 5-112)  months. The median time to relapse was 48 versus 34 months in the RTX versus non-RTX groups (P = 0.727). One patient in the RTX group died presumably of heart failure. No major adverse event was observed. During the median follow-up of 81 (range 9-355)  months, no patients developed end-stage renal disease.

Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

Previous studies suggest that increased cerebrovascular reactivity might be a feature of patients who have migraine with aura (MwA). The correlation between the clinical presentation of migraine with aura and transcranial Doppler parameters remains unclear.

The main aim of this study was to explore cerebral blood flow, vascular resistance, and cerebrovascular reactivity in women MwA. Also, the relationships between hemodynamic conditions and aura characteristics are examined.

Cross-sectional study.

Headache Center, Neurology Clinic, Clinical Center of Serbia.

Fifty-four women MwA and 49 healthy controls (HCs).

Transcranial Doppler sonography examination was used to determine blood flow mean velocity (MV) and pulsatility index (PI), as well as breath-holding index (BHI), in 15 arterial segments comprising the circle of Willis.

A total of 54 women MwA and 49 HCs were studied. The PIs of all segments of the left and right middle cerebral arteries and the left and right anterior cerebral arteries were significantly higher in MwA with regards to HCs. Also, both the left and right BHIs were significantly higher in MwA than HCs. In addition, MVs of the right vertebral artery and the first segment of the basilar artery were significantly lower in MwA than HCs. Longer duration of migraine aura showed a weak negative correlation with the PI of the left posterior cerebral artery.

Our findings suggest increased vessel pulsatility, abnormal cerebrovascular reactivity, and decreased cerebral blood flow velocity in several arterial segments of the Willis circle in women MwA.

Our findings suggest increased vessel pulsatility, abnormal cerebrovascular reactivity, and decreased cerebral blood flow velocity in several arterial segments of the Willis circle in women MwA.

Multisite chronic pain (MSCP) is associated with increased chronic pain impact, but methods for identifying MSCP for epidemiological research have not been evaluated.

We assessed the validity of identifying MSCP using electronic health care data compared with survey questionnaires.

Stratified random samples of adults served by Kaiser Permanente Northwest and Washington (N = 2,059) were drawn for a survey, oversampling persons with frequent use of health care for pain. MSCP and single-site chronic pain were identified by two methods, with electronic health care data and with self-report of common chronic pain conditions by survey questionnaire. Analyses were weighted to adjust for stratified sampling.

MSCP was somewhat less common when ascertained by electronic health records (14.7% weighted prevalence) than by survey questionnaire (25.9% weighted prevalence). Agreement of the two MSCP classifications was low (kappa agreement statistic of 0.21). Ascertainment of MSCP with electronic health records was 30.9% sensitive, 91.0% specific, and had a positive predictive value of 54.5% relative to MSCP identified by self-report as the standard. After adjusting for age and gender, patients with MSCP identified by either electronic health records or self-report showed higher levels of pain-related disability, pain severity, depressive symptoms, and long-term opioid use than persons with single-site chronic pain identified by the same method.

Identification of MSCP with electronic health care data was insufficiently accurate to be used as a surrogate or screener for MSCP identified by self-report, but both methods identified persons with heightened chronic pain impact.

Identification of MSCP with electronic health care data was insufficiently accurate to be used as a surrogate or screener for MSCP identified by self-report, but both methods identified persons with heightened chronic pain impact.South Asian immigrants confront a growing non-communicable disease burden, a significant issue in countries such as the USA. While efforts have slowly begun to address South Asian migrant health, second-generation communities remain underserved and understudied despite facing many of the same non-communicable disease concerns. The aim of this commentary is to highlight unique health disparities contributing to the current South Asian migrant health status and identify pathways for further formative research needed to inform subsequent development, implementation, and evaluation of health interventions targeting this community. Extant peer-reviewed literature addressing second-generation South Asian health issues was used to identify key research pathways needed to address existing gaps. Specifically, we call for (a) enhancing targeted surveillance and recruitment in research and (b) collecting data to help characterize behavioral and cultural patterns that may contribute to disease onset and progression. Expanding research on second-generation South Asian migrant health may help to develop tailored and targeted interventions.Extubation failure is associated with negative outcomes making the identification of risk factors for failure paramount. Burn patients experience a high incidence of respiratory failure requiring mechanical ventilation. There is no consensus on the acceptable rate of extubation failure and many conventional indices do not accurately predict extubation outcomes in burn patients. The purpose of this study was to examine the rate of extubation failure in the burned population and to examine the impact of factors on extubation outcomes. Burn patients from a single center over 9 years were examined and included if they were intubated prior to arrival or within 48 hours of admission and underwent a planned extubation. From this cohort, a matched case-control analysis based on age, TBSA, and sex was performed of patients who succeeded after extubation, defined as not requiring reintubation within 72 hours, to those who failed. Characteristics and clinical parameters were compared to determine whether any factors could predict extubation failure. There was a 12.3% incidence of extubation failure. In the matched case-control analysis, the presence of inhalation injury was associated with extubation success. Higher heart rate and lower serum pH were associated with extubation failure. ANCOVA analysis demonstrated that a sodium trending higher before extubation was associated with more successes, possibly indicative of a lower volume status. Classic extubation criteria do not accurately predict extubation outcomes in burn patients; analysis of other parameters may be able to provide better predictions. A constellation of these parameters needs to be studied prospectively.

The primary aim was to quantify and compare the location and extent of pain in people with either episodic migraine, chronic migraine, or cervicogenic headache. A secondary aim was to examine the associations between pain extent and headache features, quality of life, and psychological distress for each headache type.

A cross-sectional, single-site, observational study.

Headache outpatient clinic.

From a sample of 390 patients, 114 patients with migraine or cervicogenic headache (48 episodic migraine, 30 chronic migraine, 36 cervicogenic headache) were eligible for the study.

Pain location and extent were determined using a novel approach for digital pain drawing acquisition and analysis. Headache features included intensity and history duration. Quality of life was measured using the SF-36 and psychological distress using the Hospital Anxiety and Depression Scale.

Overall, pain was most frequently reported in the frontal and temporal regions in patients with either episodic or chronic migraine, whereas pain was most frequent in the suboccipital region in patients with cervicogenic headache. A larger pain extent was moderately correlated with higher headache intensity (rs = 0.53, P = 0.003) and poorer quality of life (rs ranged from -0.36 to -0.40, P < 0.05) in patients with chronic migraine, whereas pain extent was associated with longer headache duration in those with cervicogenic headache (rs = 0.35, P = 0.04). No correlation was found between pain extent and psychological features for any headache type (P > 0.05).

Despite some differences, there was a large symptomatic overlap between headache types, highlighting the limitations of using pain location in the differential diagnosis of headache.

Despite some differences, there was a large symptomatic overlap between headache types, highlighting the limitations of using pain location in the differential diagnosis of headache.

The Unified Medical Language System (UMLS) integrates various source terminologies to support interoperability between biomedical information systems. In this article, we introduce a novel transformation-based auditing method that leverages the UMLS knowledge to systematically identify missing hierarchical IS-A relations in the source terminologies.

Given a concept name in the UMLS, we first identify its base and secondary noun chunks. For each identified noun chunk, we generate replacement candidates that are more general than the noun chunk. Then, we replace the noun chunks with their replacement candidates to generate new potential concept names that may serve as supertypes of the original concept. If a newly generated name is an existing concept name in the same source terminology with the original concept, then a potentially missing IS-A relation between the original and the new concept is identified.

Applying our transformation-based method to English-language concept names in the UMLS (2019AB release), a total of 39359 potentially missing IS-A relations were detected in 13 source terminologies. Domain experts evaluated a random sample of 200 potentially missing IS-A relations identified in the SNOMED CT (U.S. edition) and 100 in Gene Ontology. A total of 173 of 200 and 63 of 100 potentially missing IS-A relations were confirmed by domain experts, indicating that our method achieved a precision of 86.5% and 63% for the SNOMED CT and Gene Ontology, respectively.

Our results showed that our transformation-based method is effective in identifying missing IS-A relations in the UMLS source terminologies.

Our results showed that our transformation-based method is effective in identifying missing IS-A relations in the UMLS source terminologies.Cost-effectiveness studies of early intervention services (EIS) for psychosis have not included extension beyond the first 2 years. We sought to evaluate the cost-effectiveness of a 3-year extension of EIS compared to regular care (RC) from the public health care payer's perspective. Following 2 years of EIS in a university setting in Montreal, Canada, patients were randomized to a 3-year extension of EIS (n = 110) or RC (n = 110). Months of total symptom remission served as the main outcome measure. Resource use and cost data for publicly covered health care services were derived mostly from administrative systems. The incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were produced. Relative cost-effectiveness was estimated for those with duration of untreated psychosis (DUP) of 12 weeks or less vs longer. Extended early intervention had higher costs for psychiatrist and nonphysician interventions, but total costs were not significantly different. The ICER was $1627 per month in total remission. For the intervention to have an 80% chance of being cost-effective, the decision-maker needs to be willing to pay $5942 per month of total symptom remission. DUP ≤ 12 weeks was associated with a reduction in costs of $12 276 even if no value is placed on additional months in total remission. Extending EIS for psychosis for people, such as those included in this study, may be cost-effective if the decision-maker is willing to pay a high price for additional months of total symptom remission, though one commensurate with currently funded interventions. Cost-effectiveness was much greater for people with DUP ≤12 weeks.

The numeric rating scale (NRS), which does not capture the multidimensional experience of pain, is commonly used to measure pain in the emergency department (ED). In this study, we assess the utility and feasibility of the Brief Pain Inventory-Short Form (BPI-SF) in the ED.

This was a cross-sectional, prospective, convenience sample study of adult patients presenting to the ED with chest, abdominal, or musculoskeletal pain. Using confirmatory factor analysis, we investigated the construct validity of the BPI-SF. We determined the association between NRS and BPI-SF scores. We assessed the feasibility and utility of administering the BPI-SF in the ED setting by evaluating 1) the time required to complete the BPI-SF and 2) how patients perceive the BPI-SF compared with the NRS.

One hundred participants were included for analysis. The median NRS pain level on ED arrival (interquartile range [IQR]) was 7 (5-8). The median BPI-SF score (IQR) was 57 (43-73) on a 0-110 scale. Fit indices for the two-factor structure were statistically superior when compared with the one-factor model of the BPI-SF (comparative fit index 0.90 vs 0.64). Higher pain severity score, pain interference score, and total BPI-SF score were associated with higher NRS scores (P < 0.01). The mean time needed to complete the BPI-SF (SD) was 3 minutes 47 seconds (1 minute 35 seconds). Seventy-three percent of the patients preferred the BPI-SF to the NRS for pain assessment in the ED.

Our study demonstrates the validity, feasibility, and utility of the BPI-SF in the ED setting.

Our study demonstrates the validity, feasibility, and utility of the BPI-SF in the ED setting.

To determine whether actigraphy-assessed indices of sleep are associated with cognitive performance in women, and explore whether these associations vary by race/ethnicity.

Participants were 1,126 postmenopausal community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN); 25% were black, 46% white, 13% Chinese, 11% Japanese, and 5% Hispanic. Actigraphy-assessed sleep measures included total sleep time, wake after sleep onset (WASO), and fragmentation. Cognitive measures included immediate and delayed verbal memory, working memory, and information processing speed. All measures were assessed in conjunction with SWAN annual visit 15.

Across the sample, after covariate adjustment, greater WASO and fragmentation were concurrently associated with slower information processing speed. Black participants had significantly worse sleep relative to other race/ethnic groups. Significant race/sleep interactions were observed; in black, but not white, particien. This effect may not have been detected in white women because their sleep was largely within the normal range. Future longitudinal studies in diverse samples are critical to further understand whether race/ethnicity moderates the influence of sleep on cognitive performance.

Latinos are 1.5 times as likely to develop Alzheimer's dementia as non-Latino Whites. This health disparity may arise from multiple influences with culturally relevant factors receiving increasing attention. Models of acculturation stress the importance of considering acculturation-related factors within the context of socioenvironmental factors to better capture the Latino experience in the United States.

We measured 10 acculturation and contextually-related variables in 199 Latinos (age 69.7 years) without dementia participating in Rush Alzheimer's Disease Center studies. We tested the relationship between these variables via Principal Component Analysis (PCA), then investigated how resulting components associated with level of and longitudinal change in global and domain-specific cognition using separate linear mixed-effects models adjusted for relevant confounders and their interactions with time.

The PCA revealed a 3-factor unrotated solution (variance explained ~70%). Factor 1, representing accultion and lived experiences when evaluating cognition in older Latinos.

The omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important for brain development and cognitive performance. Because they are semi-essential fatty acids, they must be obtained from food. However, the dietary reference intakes of DHA and EPA have not yet been established. In women, a low DHA and/or EPA serum level during pregnancy or breastfeeding might negatively affect their children. For this study, we conducted a systematic review and meta-analysis of randomized control trials on the association between the consumption of fish oil supplements in pregnant and/or breastfeeding women and the cognitive performance of their children.

The PubMed, Embase, and Central literature databases were systematically searched. We included and extracted relevant studies in duplicate and assessed study quality. Cognitive outcomes were grouped according to published criteria and according to time elapsed after the intervention. We performed fixed-effects metaf reliably measuring cognitive performance in small children. Blood levels of omega-3 long-chain polyunsaturated fatty acids were mostly not comparable. Furthermore, the influence of genetic and environmental factors could not be assessed. Studies in this field should address such shortcomings.

Restless legs syndrome (RLS) is a sensory-motor neurological disorder. Low dose opioid medications are prescribed for treatment-refractory RLS. We describe baseline and 1-year longitudinal dosing and symptom outcomes for the National RLS Opioid Registry.

Individuals currently taking a prescribed opioid for diagnosed RLS are included in the registry. Information on initial and current opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric history, and opioid abuse risk factors were collected at baseline. Follow-up online surveys were performed at 6 months and 1-year.

Participants (n = 500) are primarily white, elderly, educated, and retired. Half of all subjects are on opioid monotherapy. Nearly 50% of all subjects are taking methadone, and one-quarter are taking oxycodone formulations. The median total daily opioid dose is 30.0 morphine milligram equivalents (MME). At baseline, three-quarters of registry participants had been taking a prescribed opioid for R predictable features.

Immunoassays based on label-free technologies (label-free immunoassay [LFIA]) offer an innovative approach to clinical diagnostics and demonstrate great promise for therapeutic drug monitoring (TDM) of monoclonal antibody (mAb) drugs. An LFIA measures immunocomplex formation in real time and allows for quantification on initial binding rate, which facilitates fast measurement within a few minutes.

Based on thin-film interferometry (TFI) technology, open-access LFIAs were developed for the quantification of the mAb drugs adalimumab (ADL) and infliximab (IFX) and for the detection of the antidrug antibodies (ADAs) to the mAb drugs (ADL-ADAs and IFX-ADAs).

The LFIAs for active mAb drugs (ADL and IFX) and for ADAs (ADL-ADAs and IFX-ADAs) were validated. The analytical measurement range (AMR) for both ADL and IFX was from 2 to 100 μg/mL. The AMR for ADL-ADAs was from 5 to 100 μg/mL and for IFX-ADAs was 10 to 100 μg/mL. In the comparison of LFIAs and reporter gene assays, the correlation coefficient was 0.972 for the quantification of ADL and 0.940 for the quantification of IFX. The concordance rate was 90% for the detection of ADL-ADAs and 76% for the detection of IFX-ADAs.

The LFIAs for active mAb drugs and ADAs were appropriate for the TDM of ADL and IFX. The TFI technology has unique advantages compared with other technologies used for the measurement of mAb drugs. Label-free technologies, especially those allowing for open-access LFIAs, have great potential for clinical diagnostics.

The LFIAs for active mAb drugs and ADAs were appropriate for the TDM of ADL and IFX. The TFI technology has unique advantages compared with other technologies used for the measurement of mAb drugs. Label-free technologies, especially those allowing for open-access LFIAs, have great potential for clinical diagnostics.