Background
The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions.
Objectives
Two ...study designs were used to assess incidence and risks of autoimmune conditions in the GRC.
Methods
Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists’ review of consenting responders’ medical records. Nested case‐control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex‐specific and sensitivity analyses were performed. GRC age‐ and sex‐adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases.
Results
Six hundred and twenty‐eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case‐control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio OR = 1.03, 95% confidence interval CI = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's.
Conclusions
The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.
Saline (0.9%, 285 mOsm) and Hartmann’s solution (255 mOsm) are two commonly used joint irrigation solutions that alter the extracellular osmolarity of in situ chondrocytes during articular surgery. ...We asked whether varying the osmolarity of these solutions influences in situ chondrocyte death in mechanically injured articular cartilage. We initially exposed osteochondral tissue harvested from the metacarpophalangeal joints of 3-year-old cows to solutions of 0.9% saline and Hartmann’s solution of different osmolarity (100–600 mOsm) for 2 minutes to allow in situ chondrocytes to respond to the altered osmotic environment. The full thickness of articular cartilage then was “injured” with a fresh scalpel. Using confocal laser scanning microscopy, in situ chondrocyte death at the injured cartilage edge was quantified spatially as a function of osmolarity at 2.5 hours. Increasing the osmolarity of 0.9% saline and Hartmann’s solution to 600 mOsm decreased in situ chondrocyte death in the superficial zone of injured cartilage. Compared with 0.9% saline, Hartmann’s solution was associated with greater chondrocyte death in the superficial zone of injured cartilage, but not when the osmolarity of both solutions was increased to 600 mOsm. These experiments may have implications for the design of irrigation solutions used during arthroscopic and open articular surgery.
An assessment of the steroid estrogen removing performance of 23 different sewage treatment plants (STPs) was performed. The assessment relied on a model to estimate influent concentrations, and ...completed questionnaires on the STP treatment details from the relevant water companies. This information was compared with observed effluent 17β-estradiol (E2) and estrone (E1) concentrations. The 10 biological filter plants (BFP) in the study performed poorly with only 30% (SD 31) removal on average for E1. This reduced E1 removal performance of the BFPs compared to all the other STP types in the survey was statistically significant (
p
<
0.001). Scenarios of all the STPs as activated sludge types, and one as all BFP types were modelled using the GREAT-ER model set up for the Aire/Calder catchment in the UK. This difference was shown to have an important effect on predicted river E1 concentrations and consequent risk classifications.
Biological (trickling) filter sewage plants are less successful than other secondary sewage treatment plants at removing estrone from sewage effluent.
Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal ...period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population.
PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation). Eligible children were aged 6-12 years and did not have severe congenital abnormalities, cardiopulmonary defects, neurodevelopmental impairment, diabetes, or any glucocorticoid use within the preceding 3 months. Participants were randomly assigned (1:1) to receive 125 μg fluticasone propionate or placebo twice daily for 12 weeks. Participants were stratified for sex, age, bronchopulmonary dysplasia diagnosis, and recent respiratory symptoms using the biased-coin minimisation technique. The primary outcome was change in pre-bronchodilator forced expiratory volume in 1 s (FEV
) after 12 weeks of treatment. Data were analysed by intention-to-treat (ie, all participants who were randomly assigned and took at least the tolerance dose of the drug). All participants were included in the safety analyses. This trial is registered at the Australian and New Zealand Clinical Trials Registry, number 12618000781246.
Between Oct 23, 2018, and Feb 4, 2022, 170 participants were randomly assigned and received at least the tolerance dose (83 received placebo and 87 received inhaled corticosteroid). 92 (54%) participants were male and 78 (46%) were female. 31 participants discontinued treatment before 12 weeks (14 in the placebo group and 17 in the inhaled corticosteroid group), mostly due to the impact of the COVID-19 pandemic. When analysed by intention-to-treat, the change in pre-bronchodilator FEV
Z score over 12 weeks was -0·11 (95% CI -0·21 to 0·00) in the placebo group and 0·20 (0·11 to 0·30) in the inhaled corticosteroid group (imputed mean difference 0·30, 0·15-0·45). Three of 83 participants in the inhaled corticosteroid group had adverse events requiring treatment discontinuation (exacerbation of asthma-like symptoms). One of 87 participants in the placebo group had an adverse event requiring treatment discontinuation (inability to tolerate the treatment with dizziness, headaches, stomach pains, and worsening of a skin condition).
As a group, children born very preterm have only modestly improved lung function when treated with inhaled corticosteroid for 12 weeks. Future studies should consider individual phenotypes of lung disease after preterm birth and other agents to improve management of prematurity-associated lung disease.
Australian National Health and Medical Research Council, Telethon Kids Institute, and Curtin University.
Evidence regarding the prevalence of expiratory flow limitation (EFL) during exercise and the ventilatory response to exercise in children born preterm is limited. This study aimed to determine the ...prevalence of EFL as well as contributing factors to EFL and the ventilatory response to exercise in preterm children with and without bronchopulmonary dysplasia (BPD). Preterm children (≤32 weeks gestational age) aged 9-12 years with (n=64) and without (n=42) BPD and term controls (n=43), performed an incremental treadmill exercise test with exercise tidal flow-volume loops. More preterm children with BPD (53%) had EFL compared with preterm children without BPD (26%) or term controls (28%) (p<0.05). The presence of EFL was independently associated with decreased forced expiratory volume in 1 s/forced vital capacity z-score and lower gestational age (p<0.05). There was no difference in peak oxygen uptake between preterm children with BPD and term controls (48.0
48.4 mL·kg
·min
; p=0.063); however, children with BPD had a lower tidal volume at peak exercise (mean difference -27 mL·kg
, 95% CI -49- -5; p<0.05). Children born preterm without BPD had ventilatory responses to exercise similar to term controls. Expiratory flow limitation is more prevalent in children born preterm with BPD and is associated with airway obstruction and a lower gestational age.
Objectives
During arthroscopic or open joint surgery, articular cartilage may be subjected to mechanical insults by accident or design. These may lead to chondrocyte death, cartilage breakdown and ...posttraumatic osteoarthritis. We have shown that increasing osmolarity of routinely used normal saline protected chondrocytes against injuries that may occur during orthopedic surgery. Often several liters of irrigation fluid are used during an orthopedic procedure, which is usually kept at room temperature, but is sometimes chilled. Here, we compared the effect of normal and hyperosmolar saline solution at different temperatures on chondrocyte viability following cartilage injury using in vitro and in vivo models of scalpel-induced injury.
Design
Cartilage injury was induced in bovine osteochondral explants and the patellar groove of rats in vivo by a single pass of a scalpel blade in the presence of normal saline (300 mOsm) or hyperosmolar saline solution (600 mOsm, sucrose addition) at 4°C, 21°C, or 37°C. Chondrocytes were fluorescently labeled and visualized by confocal microscopy to assess cell death.
Results
Hyperosmolar saline reduced scalpel-induced chondrocyte death in both bovine and rat cartilage by ~50% at all temperatures studied (4°C, 21°C, 37°C; P < 0.05). Raising temperature of both irrigation solutions to 37°C reduced scalpel-induced cell death (P < 0.05).
Conclusions
Increasing the osmolarity of normal saline and raising the temperature of the irrigation solutions to 37°C reduced chondrocyte death associated with scalpel-induced injury in both in vitro and in vivo cartilage injury models. A hyperosmolar saline irrigation solution at 37°C may protect cartilage by decreasing the risk of chondrocyte death during mechanical injury.
Historians have long been aware of a text purporting to contain decisions made by the burgesses of four Scottish burghs: Berwick, Roxburgh, Edinburgh and Stirling. This text is internally dated to ...1295 or 1296 and purports to lay down rules governing succession to deceased burgesses, some of which have echoes in modern Scots succession law. The text of the decisions has attracted little study, in part because of its complex manuscript tradition. This article draws on important recent work on the Scottish legal manuscript traditions, to explore the transmission of the decisions and what they meant to those who first articulated them. In the process, it also asks about the interaction between the manuscript traditions that transmitted the legal texts and the traditional customary practices of Scottish burghs. These questions may have some bearing on how historians understand the development of the Scottish legal tradition during the medieval period.
Background
Oclacitinib is a selective Janus kinase inhibitor for the treatment of canine allergic pruritus and atopic dermatitis in dogs. Glucocorticoids and ciclosporin increase urinary tract ...infection (UTI) frequency in dogs with inflammatory skin disease.
Objective
Prospective study to evaluate the frequency of UTI and subclinical bacteriuria in dogs with allergic dermatitis receiving oclacitinib.
Methods
Client‐owned dogs ≥2 years of age with a history of allergic dermatitis without apparent history of urinary tract disease or predisposition to UTI were included. Prior to enrolment, urinalysis and quantitative urine culture were performed after a washout period of at least 14 days from systemic antimicrobial drugs and 28 days for ciclosporin and systemic glucocorticoids. Dogs received oclacitinib at labelled dosing for an intended period of 180–230 days with a follow‐up urinalysis and urine culture performed regardless of urinary tract signs. Systemic antimicrobial and immune‐modulating drugs were not administered during the study.
Results
None of the 55 dogs in this study developed UTI while receiving oclacitinib based on follow‐up urinalysis and urine culture performed during a range of 58–280 days (mean 195 days). Two dogs developed self‐limiting abnormal urinary tract signs without urine culture or urinalysis findings consistent with UTI.
Conclusions and clinical importance
These findings indicate that bacteriuria is not an expected adverse effect in dogs treated with oclacitinib without a prior history of UTI or predisposing condition during this treatment period. Therefore, routine urine culture is not indicated for such dogs in the absence of abnormal urinalysis or clinical signs of urinary tract disease.
Résumé
Contexte
L'oclacitinib est un inhibiteur sélectif de Janus kinase indiqué dans le traitement du prurit allergique du chien et de la dermatite atopique canine. Les corticoïdes et la ciclosporine augmentent la fréquence des infections du tractus urinaire (UTI) chez les chiens atteints de dermatoses inflammatoires.
Objectifs
Une étude prospective pour évaluer la fréquence des UTI et des bactériuries subcliniques chez les chiens atteints de dermatites allergiques recevant de l'oclacitinib.
Méthodes
Les chiens de propriétaires ≥ 2 ans avec des commémoratifs de dermatite allergique sans antécédents de maladie urinaire ou de prédisposition aux UTI ont été inclus. Avant l'inclusion, une analyse et une culture urinaire quantitative ont été réalisées après une période de sevrage d'au moins 14 jours d'antibiotiques systémiques et de 28 jours de ciclosporine et de corticoïdes systémiques. Les chiens recevant de l'oclacitinib aux doses recommandées pendant une période de 180‐230 jours avec un suivi d'analyses urinaires et de cultures urinaires réalisées en fonction des symptômes d'atteintes du tractus urinaire. Les antimicrobiens systémiques et les médicaments immunomodulateurs n'ont pas été administrés au cours de l’étude.
Résultats
Aucun des 55 chiens de cette étude n'ont développé d’UTI pendant l'administration d'oclacitinib sur 58‐280 jours (moyenne 195 jours) basé sur les analyses et les cultures urinaires. Deux chiens ont développés des signes anormaux d'atteinte du tractus urinaire sans culture urinaire ou analyse correspondant à une UTI.
Conclusion et importance clinique
Ces données indiquent que la bactériurie n'est pas un effet secondaire attendu chez les chiens traités à l'oclacitinib sans antécédent d’UTI ou de conditions prédisposantes au cours de cette période de traitement. Ainsi, Une culture de routine n'est pas indiquée pour ces chiens en l'absence d'analyse urinaire anormale ou de signes cliniques d'atteinte du tractus urinaire.
Resumen
Introducción
Oclacitinib es un inhibidor selectivo de Janus quinasa para el tratamiento del prurito causado por alergia y la dermatitis atópica en perros. Los glucocorticoides y la ciclosporina aumentan la frecuencia de la infección del tracto urinario (UTI) en perros con enfermedad inflamatoria de la piel.
Objetivo
Estudio prospectivo para evaluar la frecuencia de UTI y bacteriuria subclínica en perros con dermatitis alérgica tratados con oclacitinib.
Métodos
Se incluyeron perros ≥2 años de edad con historia de dermatitis alérgica, pero sin historia de aparente enfermedad urinaria o predisposición a UTI. Antes de la inclusión en el grupo de estudio, se realizaron análisis de orina y cultivo cuantitativo de orina después de un período de lavado de al menos 14 días sin antimicrobianos sistémicos y 28 días para ciclosporina y glucocorticoides sistémicos. Los perros recibieron oclacitinib a las dosis recomendadas durante un período previsto de 180‐230 días con análisis de orina de seguimiento y cultivo de orina realizado independientemente de los signos de las vías urinarias. Durante el estudio no se administraron fármacos antimicrobianos sistémicos ni inmunomoduladores.
Resultados
Ninguno de los 55 perros en este estudio desarrolló UTI mientras recibía oclacitinib basado en los resultados del análisis de orina y el cultivo de orina realizados como seguimiento durante un periodo de 58‐280 días (media 195 días). Dos perros desarrollaron signos clinicos de enfermedad del tracto urinario auto‐limitantes sin resultados de cultivo de orina o de análisis de orina indicativos de ITU.
Conclusiones e importancia clínica
Estos hallazgos indican que la bacteriuria no es un efecto adverso esperado en perros tratados con oclacitinib que no tuviesen antecedentes previos de UTI o condiciones predisponentes durante este período de tratamiento. Por lo tanto, el cultivo de orina de rutina no está indicado para tales perros en ausencia de análisis de orina anormal o de signos clínicos de enfermedad del tracto urinario.
Zusammenfassung
Hintergrund
Oclacitinib ist ein selektiver Januskinase Inhibitor zur Behandlung von allergischem Juckreiz beim Hund, sowie der atopischen Dermatitis des Hundes. Glucocortikoide und Ciclosporin erhöhen die Häufigkeit von Harnwegsinfektionen (UTI) bei Hunden mit entzündlicher Hauterkrankung.
Ziel
Durchführung einer prospektiven Studie zur Evaluierung der Häufigkeit von UTI und subklinischer Bakteriurie bei Hunden mit allergischer Dermatitis, die Oclacitinib erhalten.
Methoden
Es wurden Hunde in Privatbesitz im Alter von ≥ 2 Jahren mit der Anamnese einer allergischen Dermatitis ohne offensichtliche Anamnese einer Harnwegsinfektion oder Prädisposition für UTI inkludiert. Vor Aufnahme in die Studie wurde nach einer Wash‐Out Periode von mindestens 14 Tagen für systemische Antibiotika und 28 Tagen für Ciclosporin und systemischen Glucokortikoiden eine Urinanalyse und eine quantitative Urinkultur durchgeführt. Die Hunde erhielten Oclacitinib in der vorgegebenen Dosierung für eine beabsichtigte Zeitspanne von 180‐230 Tage. Unabhängig von Zeichen des Harntraktes wurde eine Follow‐Up Urinanalyse und eine Urinkultur durchgeführt. Es wurden während der Studie keine systemischen Antibiotika und immunmodulierenden Medikamente verabreicht.
Ergebnisse
Aufgrund der Follow‐Up Urinanalyse und der Harnkultur, die während einer Spanne von 58‐280 Tagen (Durchschnitt 195 Tage) durchgeführt wurde, konnte festgestellt werden, dass keiner der 55 Hunde in der Studie eine UTI während er Oclacitinib erhielt, entwickelte. Bei zwei Hunden traten selbstlimitierende abnormale Zeichen des Harntrakts auf ohne dass die Harnkultur oder die Befunde der Urinanalyse auf eine UTI hingewiesen hätten.
要約
背景
オクラシチニブは犬のアレルギー性掻痒症およびアトピー性皮膚炎の治療のための選択的ヤーヌスキナーゼ阻害剤である。グルココルチコイドおよびシクロスポリンは、炎症性皮膚疾患を有する犬に対して尿路感染症(UTI)の頻度を増加させる。
目的
オクラシチニブを投与されたアレルギー性皮膚炎の犬におけるUTIおよび無症候性の細菌性尿症の発生頻度を評価するための前向き研究。
方法
尿路疾患の明らかな病歴がなく、UTIの発症素因のない、アレルギー性皮膚炎の病歴を有する2歳以上の飼い犬が組み入れられた。組み入れ前に、全身性抗菌薬については少なくとも14日間の休薬期間後、シクロスポリンおよび全身性グルココルチコイドについては28日間の休薬期間後に、尿検査および定量尿培養を実施した。犬は予め設定された180‐230日の期間中(平均195日)に、推奨量のオクラシチニブを内服することとし、尿路症状に関係なく尿検査および尿培養を追跡検査した。調査期間中、全身性抗菌薬および免疫調節薬は投与されなかった。
結果
58‐280日(平均195日)の調査期間中、オクラシチニブ治療を受けた55頭に、追跡検査された尿検査および尿培養の結果に基づいて、UTIと診断された犬はいなかった。2頭の犬が、自然治癒性の異常な尿路症状を示したが、尿培養および尿検査所見はUTIと一致しなかった。
結論および臨床的な重要性
これらの知見は、UTIの既往歴または素因がない犬では、本治療期間中においては、細菌尿症はオクラシチニブの予期される副作用ではない示唆する。したがって、異常な尿検査または尿路疾患の臨床徴候がない犬では、定期的な尿培養は必要ないことが示唆される。
摘要
背景
奥拉替尼是一种选择性Janus激酶抑制剂,可以治疗犬的过敏性瘙痒和异位性皮炎。糖皮质激素和环孢素治疗犬的炎性皮肤病,尿道感染的发病率较高。
目的
用奥拉替尼治疗犬过敏性皮炎,前瞻性研究评估其尿道感染和亚临床细菌尿的发病频率。
方法
大于2岁有过敏性皮炎的家养犬,未见尿道疾病病史,也无尿道感染易感性。停用抗生素14天,停用环孢素和全身性糖皮质激素28天后,在加入本研究前,进行尿液分析和定量尿培养。按照说明书剂量给予犬预期180‐230天的奥拉替尼,随后不论是否出现尿道症状,都进行尿液分析和尿培养。在研究期间,不使用全身性抗微生物药和免疫调节剂。
结果
参与研究的55只犬,给予时长为58‐280天(平均195天)的奥拉替尼,基于尿液分析和尿培养,未见任何犬出现尿道感染。两只犬出现自限性异常尿道症状,但培养或尿液分析未发现尿道感染。
结论和临床意义
这些发现说明,对于无尿道感染病史和不易感的犬来说,奥拉替尼治疗犬没有细菌尿的副反应。因此,如果这类犬,如果未见异常的尿道症状,无须进行常规的尿液培养。
Resumo
Contexto
O oclacitinib é um inibidor seletivo de Janus Kinase usado no tratamento de prurido alérgico e dermatite atópica em cães. Os glicocorticoides e a ciclosporina aumentam a frequência de infecções do trato urinário (ITU) em cães com dermatopatias inflamatórias.
Objetivo
Avaliar prospectivamente a frequência de ITU e bacteriúria subclínica em cães com dermatite alérgica recebendo oclacitinib.
Métodos
Foram incluídos cães de proprietários, com mais de dois anos de idade, histórico de dermatite alérgica e sem histórico aparente de doenças do trato urinário ou predisposição a ITU. Antes da inclusão, foram realizadas urinálise e cultura de urina quantitativa. Os cães deveriam estar sem antibióticos sistêmicos por pelo menos 14 dias e sem ciclosporina ou glicocorticoides por pelo menos 28 dias antes da inclusão. Os animais receberam oclacitinib na dose recomendada na bula, por um período desejado de 180‐230 dias, com acompanhamento através de urinálise e urocultura independente da presença de sinais clínicos de ITU. Antimicrobianos sistêmicos e drogas imunomoduladoras não foram realizadas durante o estudo.
Resultados
Nenhum dos 55 cães do estudo desenvolveu ITU durante a terapia com oclacitinib baseado na urininálise e urocultura realizadas durante um período entre 58‐280 dias (média de 195 dias). Dois cães desenvolveram sinais c
TBT Causes Regime Shift in Shallow Lakes Sayer, Carl D; Hoare, Daniel J; Simpson, Gavin L ...
Environmental science & technology,
09/2006, Letnik:
40, Številka:
17
Journal Article
Recenzirano
Tributyltin (TBT) is an organotin compound used since the early 1960s as a biocide in boat antifouling paints. Its use has been linked to a host of negative effects in marine ecosystems including ...malformations and imposex in Mollusca and acute toxicity in many other aquatic animals. Yet, the consequences of TBT use in freshwaters are largely unknown. Here, for the first time we reveal that TBT may have caused hitherto unsuspected damage to freshwater ecosystems. Through an analysis of dated sediment cores collected from a system of recreationally boated, shallow lakes, we show that first evidence of TBT is associated with a dramatic loss of submerged vegetation and associated diverse animal communities. Cause and effect are difficult to unravel in our study. However, we hypothesize that TBT, through reducing populations of grazing organisms in lakes already affected by eutrophication, promoted the replacement of macrophytes by phytoplankton, ultimately leading to a regime shift in the ecosystem. Our findings may have parallels in freshwater ecosystems all over the world.
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