Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level.

BACKGROUND: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology. METHODS: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients. FINDINGS: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71]). INTERPRETATION: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice. FUNDING: The Italian Ministry of Health - Ricerca Corrente.

Subclinical ultrasound synovitis in a particular joint is associated with ultrasound evidence of bone erosions in that same joint in rheumatoid patients in clinical remission.

OBJECTIVES: The main aim of this study was to investigate the relationship between ultrasound (US) findings indicative of joint inflammation and US features characterising bone erosions at joint level in patients with rheumatoid arthritis (RA) in clinical remission. METHODS: Twenty-four consecutive patients with RA in clinical remission according to EULAR criteria (DAS28<2.6) underwent a complete clinical assessment. An experienced sonographer blind to the clinical data performed the US examinations to detect and score signs of joint inflammation and bone erosions from second to fifth metacarpophalangeal (MCP) joints of both hands. All joints were scanned both on dorsal and volar aspects. The second and fifth MCP joints were scanned also in lateral aspects. RESULTS: The patients were mainly female (79.2%), with a mean age of 63.2 years ±12.3 standard deviation (SD) and a mean disease duration of 114.5 months ±53.9 SD. Half of the patients were rheumatoid factor positive and 45.8% were anti-citrullinated protein antibody positive. A total of 192 MCP joints and 480 aspects were assessed. Of these joints, 105 (54.7%) were found inflamed by grey-scale US, 57 (29.7%) were power Doppler (PD) positive, and bone erosions were detected in 42 (21.7%) joints. PD signal was found in 30 (53.6%) of the 56 eroded aspects and in only 41 (9.7%) out of the 424 aspects without bone erosions. Both the GS and PD mean scores were statistically higher in the joints with US bone erosions compared to those without erosions. CONCLUSIONS: A higher prevalence of PD signal was found in the joints where bone erosions were detected. This is the first study providing evidence supporting the association between US bone erosions and the persistence of subclinical inflammation in RA patients in clinical remission.

Exhaled nitric oxide and screening for occupational asthma in two at-risk sectors: bakery and hairdressing.

BACKGROUND: Fractional exhaled nitric oxide (FENO) levels are increasingly being used in the diagnosis and management of asthma. However, this indicator has rarely been used to detect occupational asthma. OBJECTIVE: To examine non-invasive methods to estimate airway inflammation. METHODS: A nested case-control study was conducted among a retrospective cohort of young workers in the bakery, pastry-making and hairdressing industries. Subjects underwent a clinical examination during a medical visit. Blood samples were collected and FENO levels measured. Cases were subjects diagnosed as suffering from 'confirmed' or 'probable' occupational asthma. RESULTS: Of the 178 workers included in the study, 19 were cases. In univariate analysis, FENO was associated with case/control status, and height and smoking status. In a multiple linear regression model, case/control status (P < 0.001), height (P = 0.006) and smoking status (P < 0.001) remained independent risk factors for variations in FENO levels. Good or fair sensitivity of respectively around 80% and 70% can be achieved using low FENO thresholds (8.5 and 10.5 ppb, respectively). FENO >8.5 ppb and a positive clinical examination increases specificity without loss of sensitivity (to 80.5% and 79.0%, respectively). CONCLUSION: This study suggests that FENO measurements alone cannot be considered a useful screening test for occupational asthma. Further investigations are needed to investigate the use of combined FENO and questionnaire or repeated measures.

Room-temperature ferromagnetism of all-epitaxial ß-Fe-Ge/diamond-Ge/ß-Fe-Ge trilayers.

We report on the first all-epitaxial ferromagnet/inorganic semiconductor/ferromagnet hybrid heterostructure that exhibits (i) a Ge barrier of diamond crystal structure, (ii) room-temperature ferromagnetic electrodes and (iii) very smooth interfaces. Both bottom- and top-Fe-Ge electrodes exhibit tiny in-plane magnetic anisotropies dominated by a magnetocrystalline contribution of six-fold symmetry originating from the hexagonal symmetry of the B82 (Ni2In) ß-Fe-Ge phase. A key result is the absence of any magnetic coupling between these soft-magnetic electrodes for Ge barrier thickness as low as ~2.5 nm, which allows us to easily tune the parallel and antiparallel magnetic alignments by applying suitably small magnetic fields. This confirms the beneficial use of H-surfactant in order to drastically reduce the roughness of the Ge barrier, as revealed by our scanning tunneling microscopy and transmission electron microscopy measurements. This new all-epitaxial ferromagnet/semiconductor hybrid system appears, therefore, to be a promising candidate for the realization of magnetic tunnel junctions with a single crystal semiconductor barrier that are fully compatible with Si-based technology.

GDNF expression in Wilms tumor.

PURPOSE: Wilms tumor or nephroblastoma is a developmental tumor of the kidney and one of the most frequent solid tumors in childhood. It derives from metanephrotic blastema and mimics nephrogenesis in a disorganized manner, offering an adequate model for study of human nephrogenesis. GDNF (glial cell line derived neurotrophic factor), a potent proliferation and survival factor of dopaminergic neurons, has recently been shown to have an early and major role in nephrogenesis. We studied the expression of GDNF in Wilms tumor. MATERIALS AND METHODS: The study included 20 patients with nephroblastoma whose age at surgery ranged from 2 months to 13 years. Expression of GDNF protein was analyzed by an immunohistochemical technique using anti-GDNF antibody. Presence of GDNF-messenger (m)RNA and receptors GFRalpha1 and GFRalpha2-mRNA was analyzed by reverse transcription polymerase chain reaction. Specimens were also studied to evaluate apoptosis, proliferation index and Bcl-2 expression. RESULTS: GDNF expression was mainly found in the epithelial cells of the most differentiated tubes, GDNF and co-receptors mRNA were found in specimens and proliferative activity was found on the same tubes as GDNF expression. Bcl-2 was expressed strongly in epithelial cells, in an intermediate fashion in the blastema and faintly in mesenchyma. Apoptosis was of low frequency in structures strongly expressing GDNF. CONCLUSIONS: We have shown that GDNF is expressed by nephroblastoma tissue of human kidneys. This expression is mainly in the differentiated epithelial component of the nephroblastoma. We have also shown that tissue strongly expressing GDNF is positively proliferative and has less apoptotic activity. We speculate that the role of GDNF may not be limited to normal nephrogenesis but may interact with other factors in the process of proliferation and apoptosis involved in nephroblastoma tumorigenesis.

Hepatitis A among health workers in Paris hospitals. Occupational Health Physicians of Paris Hospital (AP-HP).

To design a vaccination strategy against hepatitis A among hospital employees, we carried out a serological survey of hepatitis A virus (HAV) infection in 10 university hospitals in the Paris area. Subjects under 60 years of age were consecutively enrolled by occupational health services and tested for IgG to HAV by ELISA. Of the 1,516 subjects recruited, 926 were health workers (HW), 322 clerks, and 268 cooks or kitchen employees. Among HW and clerks the HAV seroprevalence was 53.8% (95% CI: 44.0-65.6), increasing with age and being higher among employees of African or Caribbean origin than those from Europe (83.6% vs 45.6%, P < .001). Age correlated closely with the duration of hospital work, so only age was taken into account for further analysis. The HAV seroprevalences among HW and clerks originating from Europe were close (46.8% vs 42.6%) and remained so after adjustment for age. HAV seroprevalences in HW caring for adults and those caring for children were also similar (45.2% vs 40.1%). Seroprevalence was higher in assistant nurses than in nurses (51.3% vs. 39.8%, P < .02). Among cooks and kitchen employees, 53.4% were HAV-seropositive. This study shows that hospital employees need not routinely be vaccinated against HAV; the decision should be taken by the occupational physician according to the type of work, but should be routine for cooks and kitchen employees. The need for prevaccinal screening for anti-HAV should be assessed in the light of employees' geographical origin and age.

Down-regulation of CD95 (Fas/Apo-1) in the epithelia of adenovirus-infected appendices.

AIMS: Adenoviral inclusions are commonly seen in appendices from infants with intussusception. They are associated with focal epithelial budding and less frequently with epithelial shedding. These morphological changes could depend on the opposing effects of adenoviral gene products on CD95-mediated apoptosis. METHODS AND RESULTS: Appendices from intussusceptions with viral inclusions (n = 4) and normal appendices (n = 10) were studied by immunochemistry with anti-adenovirus, anti-CD95 and anti-HLA-DR antibodies. Apoptosis was studied by the TUNEL method. The mucosa of normal appendices contained no adenoviral protein. CD95 was present in all epithelial cells except Paneth cells. HLA-DR was absent in epithelial cells and apoptosis was seen only in germinal centres and in a few surface epithelial cells. The epithelium of appendices from intussusceptions contained nuclear inclusions labelled with anti-adenovirus antibody, always found in the epithelial buds. The epithelial CD95 pattern was drastically altered in adenovirus-infected appendices. CD95 was absent from the budding foci. In these foci, HLA-DR was overexpressed. There was also increased epithelial apoptosis in areas remote from those lacking CD95 antigen. CONCLUSIONS: The appearance of epithelial budding or shedding in appendices from intussusception could be due to focal in situ differences in the expression of adenoviral genes.

Degradation of hemicellulose and pectin by horse caecum contents.

1. Polysaccharide depolymerases and glycoside hydrolases involved in the breakdown of plant structural polysaccharides (hemicellulose and pectins) were monitored in three fractions of the liquid phase of horse caecum digesta: acellular fluid (AF), bacteria (B) and protozoa plus bacteria (PB). 2. Both bacteria and protozoa were found to be involved in the decomposition of pectic substances, with two enzymic activities: depolymerase (polygalacturonase, EC 3.2.1.15; and pectin lyase, EC 4.2.2.10) and esterase (pectinesterase, EC 3.1.1.11). The activity of the PB fraction was higher than that of B. 3. With hemicellulosic substrates, all three fractions showed a significant xylan endo-1,3-beta-xylosidase (EC 3.2.1.32) activity. Mannan was hardly broken down. 4. Galactomannan and arabinogalactan were broken down more extensively by the PB fraction than by the B fraction. Glycosidase activities (xylan 1,4-beta-xylosidase, EC 3.2.1.37 and alpha-L-arabinofuranosidase, EC 3.2.1.55) were also observed.

[Attachment of horse cecum Ciliata to plant fragments. Degradation of chloroplasts. Attachment of bacteria to cecal Ciliata]. / Attachement des Ciliés du caecum de cheval aux fragments végétaux. Dégradation des chloroplastes. Attachement des bactéries aux Ciliés du caecum.

Cecum microfauna association with different plant tissues was examined by scanning and transmission electron microscopy. The ciliates were attached to the damaged areas of the leaves and their highest concentrations were found on the epidermis and mesophyll tissues. The degradation of plant tissue was due to protozoal ingestion of the plant fragments. The morphology of ingested envacuolized chloroplasts changed rapidly, showing different stages of digestion inside the ciliate endoplasm. Intact chloroplasts were rarely observed but the grana of fragmented thylakoid membranes was often seen. The chloroplasts then appeared in concentric rings resembling pseudomyelinic figures. Plastoglobuli indicated the chloroplastic origin of these figures. Cecum microflora association with the microfauna showed that the different morphological types of cecal bacteria had three ways of attaching: some appeared to be attached via small amounts of extracellular material and some by capsule - like material; others (bacilli), due to an electron-dense outer layer, were observed to adhere so closely that they conformed to the shape of the ciliate.

[Behavior of rumen ciliate populations cultured in sucrose and sucrose-urea media]. / Comportement des populations ciliaires du rumen en culture dans les milieux saccharose et saccharose-urée.

The behaviour of rumen ciliates in culture in vitro is studied according to the concentration of substrates and requirements of middle removal. The most favorable concentrations, for a best ciliate's survival is from 0.4 to 0.6 mg/ml of sucrose and 0.05 mg/ml of urea. We observe two periods in the culture: in the first, Entodinium grows essentially, in the second the population of holotrich ciliates increases. If survival is almost the same, the population is most important in culture with sucrose urea than with sucrose.