Proliferation and apoptosis dynamics of the normal canine mammary gland during the oestrous cycle evaluated by Ki-67 and Caspase-3 indexes.

Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.

Maternal vaccination against group B Streptococcus glyceraldehyde-3-phosphate dehydrogenase leads to gut dysbiosis in the offspring.

Group B Streptococcus (GBS) remains a major neonatal life-threatening pathogen. We initially identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a promising vaccine candidate against GBS. Since GAPDH is highly conserved, we investigate whether GBS GAPDH maternal vaccination interferes with the intestinal colonization of the offspring and the development of its mucosal immune system and central nervous system. An altered gut microbiome with increased Proteobacteria is observed in pups born from vaccinated dams during early life. These pups present decreased relative expression of IL-1ß, IL-17A, RegIIIγ and MUC2 in the distal colon. They also display increased CD11b, F4/80 and MHC class II expression on microglia in early life and marked reduction of Ly6C+ cells and neutrophils. Importantly, male mice born from vaccinated mothers present behavioral abnormalities during adulthood, including decreased exploratory behavior, a subtle anxious-like phenotype and global alterations in spatial learning and memory strategies, and higher sensitivity to a stressful stimulus. Our study highlights the danger of using ubiquitous antigens in maternal human vaccines against neonatal pathogens.

Poly-N-Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect.

Poly-N-acetylglucosamine (PNAG) is a major component of the Staphylococcus epidermidis biofilm extracellular matrix. However, it is not yet clear how this polysaccharide impacts the host immune response and infection-associated pathology. Faster neutrophil recruitment and bacterial clearance were observed in mice challenged intraperitoneally with S. epidermidis biofilm cells of the PNAG-producing 9142 strain than in mice similarly challenged with the isogenic PNAG-defective M10 mutant. Moreover, intraperitoneal priming with 9142 cells exacerbated liver inflammatory pathology induced by a subsequent intravenous S. epidermidis challenge, compared to priming with M10 cells. The 9142-primed mice had elevated splenic CD4(+) T cells producing gamma interferon and interleukin-17A, indicating that PNAG promoted cell-mediated immunity. Curiously, despite having more marked liver tissue pathology, 9142-primed mice also had splenic T regulatory cells with greater suppressive activity than those of their M10-primed counterparts. By showing that PNAG production by S. epidermidis biofilm cells exacerbates host inflammatory pathology, these results together suggest that this polysaccharide contributes to the clinical features associated with biofilm-derived infections.

DAS28, CDAI and SDAI cut-offs do not translate the same information: results from the Rheumatic Diseases Portuguese Register Reuma.pt.

OBJECTIVES: . The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients. Cut-off values were defined to classify the states of RA disease activity: remission, low, moderate and high. The aim of this work was to assess disease activity states classified by DAS28, CDAI and SDAI and to analyse their agreement in the Rheumatic Diseases Portuguese Register Reuma.pt. METHODS: . A total of 2795 patients and 14 440 visits were selected from Reuma.pt for analysis. Pearson's correlation coefficients (PCCs) were calculated for the three indices. McNemar's chi-squared tests, PCCs and kappa statistics were performed to analyse and compare the distribution of visits among all disease activity states and indices. RESULTS: A strong correlation was found between the three indices throughout the 14 440 visits: r = 0.874 for DAS28/CDAI, r = 0.877 for DAS28/SDAI and r = 0.984 for CDAI/SDAI (all PCCs with P < 0.0001). However, when categorization in the different disease activity states was analysed, McNemar's chi-squared tests and PCCs revealed significant disagreement between the cut-offs of the three indices. CONCLUSION: DAS28, CDAI and SDAI cut-offs do not translate into the same clinical information in Reuma.pt. Although this might be expected for the original DAS28 cut-offs, when compared with CDAI and SDAI significant disagreement was also found for the DAS28 modified cut-offs. For visits where patients are in CDAI or SDAI remission, we also find disagreement between these two indices, which may contradict previous conclusions that acute phase reactants add little to composite disease activity indices for RA.

Endocrine disruption effects of p,p'-DDE on juvenile zebrafish.

The persistent organic pollutant p,p'-DDE, the major metabolite of the insecticide DDT, has displayed evidence of endocrine disruption through the inhibition of androgen binding to androgen receptors in different species. Although p,p'-DDE was continuously detected in wild fish with abnormal gonad development such as intersex, little is known about its mode of action during gonad development in fish. To elucidate the potential endocrine effects of this pollutant in zebrafish (Danio rerio), juveniles (30 days post hatch) were exposed to p,p'-DDE during the critical window of sexual differentiation. Fish were exposed to sublethal concentrations ranging from 0.01 to 20 µg l(-1) over 14 days and were maintained in control water for an additional 4 months. As core endpoints, the vitellogenin (vtg) concentration was measured at the end of exposure, and sex ratio and the gonadosomatic index were assessed 4 months after the end of exposure. An increase in vtg production in whole body homogenate was observed in fish exposed to 0.2 and 2.0 µg l(-1) p,p'-DDE. No significant differences were displayed in morphological parameters such as the gonadosomatic index of males and females or sex ratio. However, exposed females presented histopathological changes that include the reduction of the number of mature oocytes, which might impair their successful reproduction. These results demonstrate the ability of p,p'-DDE to cause endocrine disruption in zebrafish exposed during gonad differentiation of juvenile specimens. Furthermore, vtg induction by p,p'-DDE in juvenile zebrafish arises as a predictive marker for adverse effects of this DDT metabolite on the ovarian function of female zebrafish.

A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to canine gastric mucosa with defined gastric glycophenotype.

BACKGROUND: The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. MATERIALS AND METHODS: The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. RESULTS: The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. CONCLUSIONS: The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach.

Mucosal and systemic T cell response in mice intragastrically infected with Neospora caninum tachyzoites.

The murine model has been widely used to study the host immune response to Neospora caninum. However, in most studies, the intraperitoneal route was preferentially used to establish infection. Here, C57BL/6 mice were infected with N. caninum tachyzoites by the intragastric route, as it more closely resembles the natural route of infection through the gastrointestinal tract. The elicited T-cell mediated immune response was evaluated in the intestinal epithelium and mesenteric lymph nodes (MLN). Early upon the parasitic challenge, IL-12 production by conventional and plasmacytoid dendritic cells was increased in MLN. Accordingly, increased proportions and numbers of TCRαß+CD8+IFN-γ+ lymphocytes were detected, not only in the intestinal epithelium and MLN, but also in the spleen of the infected mice. In this organ, IFN-γ-producing TCRαß+CD4+ T cells were also found to increase in the infected mice, however later than CD8+ T cells. Interestingly, splenic and MLN CD4+CD25+ T cells sorted from infected mice presented a suppressive activity on in vitro T cell proliferation and cytokine production above that of control counterparts. These results altogether indicate that, by producing IFN-γ, TCRαß+CD8+ cells contribute for local and systemic host protection in the earliest days upon infection established through the gastrointestinal tract. Nevertheless, they also provide substantial evidence for a parasite-driven reinforcement of T regulatory cell function which may contribute for parasite persistence in the host and might represent an additional barrier to overcome towards effective vaccination.

Thyroid disruption in the lizard Podarcis bocagei exposed to a mixture of herbicides: a field study.

Pesticide exposure has been related with thyroid disrupting effects in different vertebrate species. However, very little is known about the effects of these compounds in reptiles. In the Mediterranean area, lacertid lizards are the most abundant vertebrate group in agroecosystems, and have been identified as potential model species for reptile ecotoxicology. The aim of this study was to understand if the herbicides applied in corn fields have thyroid disruptive effects in the lizard Podarcis bocagei. Adult male lizards were captured in north-western Portugal in corn fields treated with herbicides (exposed sites), and in organic agricultural fields (reference sites). Thyroid and male gonad morphology and functionality, and testosterone levels were investigated through histological, immunohistochemical and biochemical techniques. Lizards from exposed locations displayed thyroid follicular lumens with more reabsorption vacuoles and significantly larger follicular area than those from reference fields. Furthermore, testes of lizards from exposed locations had significantly larger seminiferous tubule diameters, significantly higher number of spermatogenic layers and displayed an up-regulation of thyroid hormone receptors when compared with lizards from reference areas. These findings strongly suggest that the complex mixture of herbicides that lizards are exposed to in agricultural areas have thyroid disrupting effects which ultimately affect the male reproductive system. Alachlor, which has demonstrated thyroid effects in mammals, may be largely responsible for the observed effects.

CA 15-3, CRP, and LDH correlates with prognostic parameters in canine mammary neoplasms.

The identification of putative prognostic factors in canine mammary neoplasms (CMNs) has been focused on tissue-specific biomarkers, but the serum biomarkers, including cancer antigen 15-3 (CA 15-3), c-reactive protein (CRP), and lactate dehydrogenase (LDH) have been demonstrated to display clinical application in cases of CMNs. The aim of the study was to evaluate the levels of these serum biomarkers and their association with well-established prognostic factors in CMNs. Samples from 15 female canines with CMNs and 15 clinically healthy ones were collected. The results were evaluated using the Tukey's, Pearson, or Spearman tests. The cut-off point, sensitivity, specificity, and area under curve (AUC) were evaluated using the receiver operating characteristic (ROC) curve analysis in a logistic regression model (P<0.05). The levels of CA 15-3, CRP and LDH were significantly higher in the serum of female dogs with CMNs compared to the healthy ones. Moreover, these factors were positively correlated with ulceration, tumor size, histopathological grade, metastatic lymph node, and clinical staging. Female dogs with CMNs were found to exhibit highest serum levels of CA 15-3, CRP, and LDH. Therefore, they can be applied to improve the efficacy of the diagnosis and prognostic evaluation in casas of CMNs.

Portuguese recommendations for the use of biological and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis - 2020 update.

OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Embryotoxicity of silver nanomaterials (Ag NM300k) in the soil invertebrate Enchytraeus crypticus - Functional assay detects Ca channels shutdown.

Despite that silver (Ag) is among the most studied nanomaterials (NM) in environmental species and Ag's embryotoxicity is well known, there are no studies on Ag NMs embryotoxicity in soil invertebrates. Previous Full Life Cycle (FLC) studies in Enchytraeus crypticus, a standard soil invertebrate, showed that Ag materials decreased hatching success, which was confirmed to be a hatching delay effect for silver nitrate (AgNO3) and mortality for Ag NM300K. In the present study, we aimed to investigate if the impact of Ag takes place during the embryonic development, using histology and immunohistochemistry. E. crypticus cocoons were exposed to a range of concentrations of Ag NM300K (0-10-20-60-115 mg Ag/kg) and AgNO3 (0-20-45-60-96 mg Ag/kg) in LUFA 2.2 soil, in an embryotoxicity test, being sampled at days 1, 2, 3 and 6 (3, 4, 5 and 7 days after cocoon laying). Measured endpoints included the number of embryonic structures, expression of transferrin receptor (TfR) and L type calcium channels (LTCC) through histological and immunohistochemistry analysis, respectively. Results confirmed that Ag materials affected the embryonic development, specifically at the blastula stage (day 3). The expression and localization of TfR in E. crypticus was shown in the teloblasts cells, although this transcytosis mechanism was not activated. Ag affected calcium (Ca) metabolism during embryonic development: for AgNO3, LTCC was initially activated, compensating the impact, for Ag NM300K, LTCC was not activated, hence no Ca balance, with irreversible consequences, i.e. terminated embryonic development. An Adverse Outcome Pathway was drafted, integrating the mechanisms here discovered with previous knowledge.

Osteoporosis management during the COVID-19 pandemic - Position paper.

COVID-19 pandemic significantly increased the already large number of victims of osteoporosis in Portugal. Osteoporosis outpatient clinics were either closed or had limited presential appointments. Many hospitals reduced orthopaedic services to make space for patients with COVID-19. In addition, the volunteer or forced sedentarism, as imposed by the pandemic, increased the risk of falls and fractures drastically. It urges to intensify the current efforts to improve the management of bone health and to prioritize fragility fracture care and prevention. This paper addresses the challenges in osteoporosis management during the COVID-19 pandemic and provides guidance on osteoporosis management. This position paper is a joint initiative of several health professionals and patients dedicated to osteoporosis.

The role of opioid analgesics in rheumatic disorders: a position paper from the Portuguese Rheumatology Society.

Pain is a common feature of most rheumatic diseases and it is often the main reason for the patient to seek for a clinical appointment. Chronic pain has a major impact on patient's quality of life, being frequently associated with functional incapacity, sleep and mood disorders. This leads to absenteeism and heavy consumption of health resources, both representing huge burdens on national economy. Managing musculoskeletal pain is pivotal but can be challenging. The use of the available pharmaceutical armamentarium should be parsimonious. Opioids are strong analgesic drugs that mostly act through their agonist action on µ-receptors in the central nervous system. Opioid-related side effects are not negligible and are mediated through both central and peripheral opioid receptors. The use of opioids is well established in the treatment of oncologic pain but their role in the management of musculoskeletal pain is still controversial. Inflammatory rheumatic diseases, osteoarthritis, osteoporotic fractures, chronic low back pain and fibromyalgia represent diverse major rheumatic conditions that frequently lead to chronic pain. In order to standardize and optimize management of musculoskeletal chronic pain in these prevalent diseases, the Portuguese Rheumatology Society elaborated this position paper. The objectives were: a) to define the importance of pain assessment and classification; b) to guide patient selection, appropriate choice of opioids, their management, and raise awareness of their adverse effects; c) to review the existent data on possible indications of opioid therapy on rheumatic diseases.

Molecular detection of Hepatozoon felis in cats from Maio Island, Republic of Cape Verde and global distribution of feline hepatozoonosis.

BACKGROUND: Vector-borne diseases are emerging worldwide and have an important zoonotic relevance. In the last few years, the interest in vector-borne pathogens in cats has increased. However, studies on feline vector-borne pathogens on tropical islands are lacking. Islands differ from continental countries because they have an enclosed population of animals, with all year presence of the vectors and, most often, without vector control measures. This study focused on the molecular identification and phylogenetic analysis of vector-borne pathogens in autochthonous cats with a mixed indoor-outdoor lifestyle from Maio Island, Cape Verde archipelago. METHODS: Blood samples were collected from 80 asymptomatic cats, representing almost a quarter of the total cat population of the island. The presence of DNA of protozoa of the genus Hepatozoon and bacteria belonging to family Anaplasmataceae and to genus Bartonella was assessed by PCR and phylogenetic analysis was conducted. Statistical analysis was performed to identify risk factors associated with infection. For feline hepatozoonosis, a worldwide dataset of Hepatozoon felis sequences retrieved from mammal species and vectors along with Hepatozoon spp. sequences retrieved from felids was generated, phylogenetically analyzed and the geographical and host distribution was assessed. RESULTS: Hepatozoon felis genotype I was identified in 12 (15%) cats from Maio Island whereas none of the cats were PCR positive for the other pathogens tested. No significant association of H. felis infection with age, sex, location or presence of vectors was observed by statistical analysis in Cape Verde's cats. Phylogenetic analysis on the worldwide dataset of feline Hepatozoon sequences showed two significant distinct clades for H. felis genotype I and II. Different geographical distributions were assessed: H. felis genotype I was the only genotype found in Africa and has been reported worldwide, with the exception of Japan and Brazil where only H. felis genotype II has been reported. CONCLUSIONS: The identification of H. felis genotype I in cats in Maio Island highlights the need to further investigate the significance of H. felis genotypes and to clarify the epidemiological aspects of this infection.

Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors - March 2008 update. / Recomendações para o diagnóstico e tratamento das tuberculoses latente e activa nas doenças inflamatórias articulares candidatas a terapêutica com fármacos inibidores do factor de necrose tumoral alfa. Revisão de Março de 2008.

The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFα) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFα therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFα therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFα therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn's complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-α therapy, even in the presence of a negative test, after risk / benefit assessment. Rev Port Pneumol 2007; XIV (2): 271-283.

Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases for candidates for therapy with tumor necrosis factor alpha inhibitors--March 2008 update.

The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the duration is < 5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again < 5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment.

A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection.

Group B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.

Common Evaluations of Disease Activity in Rheumatoid Arthritis Reach Discordant Classifications across Different Populations.

OBJECTIVES: The classification of disease activity states in rheumatoid arthritis (RA) can be achieved through disease activity indices, such as the Disease Activity Score in 28 joints erythrocyte sedimentation rate (DAS28-ESR), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Subjective measurements, such as patient reported outcomes have been incorporated into several of these indices alongside more objective assessments, such as increases in the ESR and C-reactive protein. Moreover, while they use similar criteria, different indices weight these criteria to different extents. Therefore, the classifications based on each evaluation may not always be the same. We aim to compare the performance of the three indices and their individual components in two different populations. METHODS: Data from Dutch and Portuguese adherent centers were extracted from the METEOR database, a multinational collaboration on RA. We included a total of 24,605 visits from Dutch centers (from 5,870 patients) and 20,120 visits from Portuguese centers (from 3,185 patients). We compared the disease activity states as evaluated by the DAS28-ESR, CDAI, and SDAI across the two populations. In addition, we analyzed the individual components of each evaluation, including their respective contributions to the outcome, in each population. RESULTS: We found significant differences in the disease activity states classified with the DAS28-ESR between the two populations. SDAI and CDAI had more congruous results. While the proportion of visits to Dutch and Portuguese centers that were classified as "in remission" was very similar between the CDAI and SDAI, the DAS28-ESR gave discordant results. Dutch patients had lower ESRs, which is more heavily weighted in the DAS28-ESR. In addition, even though the mean physicians' global assessment values did not vary significantly for Dutch vs Portuguese physicians, we found that doctors at Portuguese centers overall scored the physician's global assessment lower than Dutch physicians for patient visits classified by disease activity state. CONCLUSION: While the CDAI and SDAI assigned disease activity states that were largely similar, the DAS28-ESR was often discordant across the two populations. Moreover, we found that physicians, more than patients, evaluated disease activity differently among the Portuguese and Dutch populations.

E-cadherin, beta-catenin, invasion and lymph node metastases in canine malignant mammary tumours.

Recent studies of canine malignant mammary tumours suggest that reduction of E-cadherin and/or beta-catenin correlates with invasive behaviour and lymph node metastasis. The aims of this study were to examine the interrelationships between the expression of E-cadherin and beta-catenin, and the relationship between the expression of E-cadherin and/or beta-catenin and the mode of growth and metastatic capacity of canine malignant mammary tumours. 90 spontaneous malignant tumours and local and regional lymph nodes were studied. A significant relationship was evidenced between membranous expression of E-cadherin and beta-catenin (p=0.0027), but not between E-cadherin and cytoplasmic beta-catenin. Only E-cadherin as a separate factor was significantly related to tumour invasion (p=0.0072) and lymph node metastasis (p=0.0001). Neither membranous nor cytoplasmic beta-catenin expression was significantly related to either of these phenomena.

Anticentromere antibody positive Ackerman's Syndrome with Granulomatous Anterior Uveitis.

Ackerman's Syndrome or Intersticial Granulomatous Dermatitis with Arthritis has been an issue of increasing number of reports in the last decade which had focused its heterogeneous cutaneous and rheumatologic expression besides the initial manifestations reported by Ackerman and his group. Granulomatosis anterior uveitis has not been previously described. Some patients are reported to have positive autoantibodies but association with anticentromere antibodies has not been previously described as well, to our knowledge. We report a new case of Ackerman Syndrome with cutaneous, articular and ocular involvement with positive anticentromere antibodies successfully treated with systemic steroids, methotrexate, hydroxychloroquine and cyclosporine. The ocular involvement and the association of anticentromere antibodies lead us to hypothesize that constellation of symptoms and autoimmune mechanisms of this uncommon multisystemic syndrome are yet to be clarified.