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Aboukamar, Samar Habib, Samar Tharwat, Mohamed Kamal Nassar, Manal A. Elzoheiry, Rania Atef, Manar S. Elmehankar" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Wafaa A." "apellidos" => "Aboukamar" "email" => array:2 [ 0 => "d_wafaa@mans.edu.eg" 1 => "drwafaaaboukamar@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Samar" "apellidos" => "Habib" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Samar" "apellidos" => "Tharwat" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Mohamed Kamal" "apellidos" => "Nassar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Manal A." "apellidos" => "Elzoheiry" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Rania" "apellidos" => "Atef" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "Manar S." "apellidos" => "Elmehankar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Rheumatology & Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Mansoura Nephrology & Dialysis Unit, Department of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Medical Student, Faculty of Medicine, Tanta University, Tanta, Egypt" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asociación entre toxoplasmosis y enfermedades reumáticas autoinmunes en pacientes egipcios" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune rheumatic diseases (ARDs) are multisystem chronic diseases associated with a high rate of morbidity and mortality in both developed and developing countries. ARDs include a wide disease spectrum: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). RA involves chronic synovial joint inflammation, which may proceed to severe disability.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">1,2</span></a> SLE exhibits a relapsing and remittent clinical course with very heterogeneous clinical picture, associated with multi-organ involvement.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">3</span></a> On the other hand, SSc is characterized by excessive fibrosis, vascular injuries, and immune disturbances.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">4</span></a> Geo-epidemiological studies implied that host genetic susceptibility and environmental factors, including socioeconomic status, dietary habits, environmental pollutants, ultraviolet radiation exposure, and infections act as potential risks or protective factors in the susceptibility to ARDs.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Toxoplasma gondii</span> (<span class="elsevierStyleItalic">T. gondii</span>) is an obligate intracellular protozoan that is claimed to be associated with autoimmunity. In both developed and developing countries, one-third of the populations are infected with <span class="elsevierStyleItalic">T. gondii</span>.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">6</span></a> It has a complex life cycle where cats and other felines represent the definitive host. The oocysts excreted in cat stool spread to the environment and cause infection of a very wide range of mammals and birds. During the acute stage, the parasite can invade almost all types of nucleated cells and multiplies rapidly as tachyzoites, while in the chronic stage, it targets the brain and the muscles and multiplies as bradyzoites inside true tissue cysts. Toxoplasmosis outcome is related to the immune status in humans: in immunocompetent individuals, <span class="elsevierStyleItalic">T. gondii</span> infection is usually asymptomatic and is mostly followed by a latent infection.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">7</span></a> Latent toxoplasmosis refers to the chronic form of asymptomatic toxoplasmosis which constitutes most cases, while serious disease occurs in infants and immunocompromised patients. In addition, reactivation of latent toxoplasmosis frequently occurs in immunocompromised patients and results in uncontrolled proliferation of the parasite.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Infection may contribute to the development of ARDs through molecular mimicry and epitope spreading. While molecular mimicry includes cross-reaction between the host tissue and the pathogen, epitope spreading results in activation of antigen-presenting cells by the pathogen leading to an enhanced local presentation of self-antigens that causes T cell activation.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">9</span></a> Prandota and colleagues<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">10</span></a> reviewed the association between late chronic toxoplasmosis and ARDs and highlighted the role of iron, folic acid, and iodine deficiencies that result from toxoplasmosis in the establishment of ARDs.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Increased prevalence of ARDs, resultant disability, and increased medical costs cause more economic burden, which requires more understanding of the pathophysiology of these diseases for better control. Therefore, we tried to explore the prevalence of anti-<span class="elsevierStyleItalic">Toxoplasma</span> antibodies of both IgM and IgG classes in patients with ARDs, including RA, SLE, and SSc and evaluate the association of ARDs with toxoplasmosis-related risk factors</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">This case-control study was carried out on 82 patients with ARDs (44 RA, 28 SLE, and 10 SSc). These patients were recruited from those attending the Rheumatology and Immunology Unit (inpatient and outpatient), Mansoura University Hospital, from January 2019 to February 2020. The inclusion criteria included: (a) age<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>18 years (b) classified as having one of ARDs as follows: RA was diagnosed according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for the diagnosis of RA,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">11</span></a> SLE was diagnosed as stated by the International Collaborating Clinics (SLICC) criteria,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">12</span></a> while SSc was diagnosed according to the 2013 ACR/EULAR classification criteria.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">13</span></a> Those with diabetes mellitus, hepatitis C virus, or overlap with other connective tissue diseases were excluded from the study. Sixty-one age- and sex-matched healthy controls were also enrolled in the study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients’ demographic, clinical and therapeutic data</span><p id="par0030" class="elsevierStylePara elsevierViewall">For the included ARD patients, sex, age, pregnancy outcomes, socioeconomic status, occupation, residence, and associated comorbidities were reported. All patients were asked about any previous or current significant neuro-psychiatric insults. Therapeutic history of immunosuppressive medications was also documented including corticosteroids, mycophenolate mofetil (MMF), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying antirheumatic drugs (bDMARD). All patients gave history of receiving csDMARDs.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Disease activity scores</span><p id="par0035" class="elsevierStylePara elsevierViewall">All ARD patients were evaluated by a well-trained rheumatologist. The evaluation included a comprehensive physical examination with targeted systemic evaluation. The disease activity was assessed in all patients as follows; RA patients were evaluated using Disease Activity Score-28 joints (DAS-28),<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">14</span></a> and SLE patients were evaluated by using SLE disease activity index 2000 (SLEDAI-2K),<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">15</span></a> while SSc patients were assessed with modified Rodnan skin score (mRSS).<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Toxoplasmosis risk factors</span><p id="par0040" class="elsevierStylePara elsevierViewall">All participants were asked to complete a self-administered questionnaire to evaluate risk factors of toxoplasmosis acquisition. It was designed to be easily filled. Patients of low education were guided to fill in the questionnaire. The questionnaire included the following items: chronic exposure to cats, kittens, or cat feces, ingestion of unpasteurized cow's and goat's milk, and consumption of unwashed raw vegetables.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Sampling and laboratory tests</span><p id="par0045" class="elsevierStylePara elsevierViewall">Eight ml venous blood was withdrawn from each patient on the same day of clinical evaluation. Serum samples were obtained from centrifuged blood samples were stored at −20<span class="elsevierStyleHsp" style=""></span>°C until analysis. Then, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were assessed by latex agglutination tests (Leaner Chemicals Co., Spain). Serological tests for anti-<span class="elsevierStyleItalic">T. gondii</span> IgM and IgG were assessed using ELISA kits (Catalog#: TX022G, Calbiotech, Inc., USA), following the manufacturer's instructions.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Data were analyzed using the Statistical Package of Social Science (SPSS) program for Windows (Standard version 24). The normality of data was first tested with one-sample Kolmogorov–Smirnov test. Qualitative data were defined using number and percentage. Association between categorical variables was tested using Chi-square test while Fischer exact test was used when expected cell count less than 5. Continuous variables were displayed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD (standard deviation) for normally distributed data and median (min–max) for non-normal data. The two groups were compared with Student <span class="elsevierStyleItalic">t</span> test for normal data and Mann–Whitney test for non-normal data. Significant variables entered Logistic regression model using the forward wald statistical technique to predict the most significant elements and to control for possible interactions and confounding effects. The results were considered significant when <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.05.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">This study included 82 ARD patients: 44 (53.75%) RA, 28 (34.1%) SLE, and 10 (12.2%) SSc. The mean age was 40.43<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.56 years, and 75 patients (91.5%) were females. Neuro-psychiatric manifestations were reported in 26 (31.7%) ARD patients, significantly higher than healthy controls (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.001). Anti-<span class="elsevierStyleItalic">T. gondii</span> IgM was detected in 15 (18.3%) ARD patients and in 3 (4.9%) controls (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.017). Anti-<span class="elsevierStyleItalic">T. gondii</span> IgG antibodies were also detected in 57 (69.5%) patients and 24 (39.3%) healthy controls (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.001). Noteworthy, both IgM and IgG antibodies were detected in 13 patients (15.9%) and in only 3 (4.9%) controls. Raw milk and milk products consumption showed a significant proportion in ARD patients (68.3%) compared to the controls (45.9%) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.007), as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Using DAS28 scoring system, 18 RA patients showed moderate activity, 10 with mild activity, and 9 with severe activity. Using SLEDAI scoring system, there were 12 SLE patients with moderate activity, 10 with severe activity and only 6 with mild activity. Using MRSS scoring system, 6 SSc patients showed moderate activity and 4 displayed mild activity (data not shown). There was non-significant difference regarding the relationship between IgM and IgG seropositivity of <span class="elsevierStyleItalic">T. gondii</span> and the disease activity either in RA, SLE, or SSc (IgM: <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.37, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.81, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.74 and IgG: <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.80, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.37, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.43, respectively).</p><p id="par0065" class="elsevierStylePara elsevierViewall">Patients with ARDs were assessed based on their autoimmune disease. <span class="elsevierStyleItalic">T. gondii</span> IgM was detected in 6 (21.4%) patients with SLE, 7 (15.9%) patients with RA, and only 2 (20%) with SSc, nevertheless, significant difference was reported in SLE patients versus control group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03). Contrastingly, <span class="elsevierStyleItalic">T. gondii</span> IgG was detected in 34 (77.3%) RA, 18 (64.3%) SLE, and 4 (40%) SSc patients, with significant difference in both RA and SLE patients versus the control group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03, respectively). Neuro-psychiatric manifestations were reported in 17 (60.7%) SLE patients: 4 (14.2%) cases with lupus-cerebritis and 13 (46.4%) patients with migraine with highly significant difference in comparison to RA and controls (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). In SSc patients, migraine showed significant difference compared to the controls (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Cats’ contact with RA patients showed significant difference versus control group (<span class="elsevierStyleItalic">P</span>v<<span class="elsevierStyleHsp" style=""></span>0.05), as shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Abortion was reported in 30 ARD patients (40%, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003). There was a significant difference between ARDs patients (SLE and RA) and the control group regarding history of abortion (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03). First trimester abortions were reported in most cases, followed by second trimester abortions. Fetal congenital anomalies, mostly cardiovascular malformations, were reported in 8 (10.7% <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.021) female ARD patients’ offspring with a significant difference in SLE and SSc in comparison to the control group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01), as illustrated in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Abortion displayed non-significant difference in IgM seropositive patients. However, fetal congenital anomalies showed significant difference in IgM seropositive patients (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04), compared to IgM seronegative patients (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). In addition, toxoplasmosis seropositive IgM antibodies were a robust predictor of prenatal congenital abnormalities with a statistically significant difference (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03), as illustrated in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>. There were non-significant differences between IgG seropositive and seronegative groups in terms of fetal congenital abnormalities or history of abortion (<a class="elsevierStyleCrossRefs" href="#tbl0020">Tables 4 and 5</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Interestingly, neither neuro-psychiatric manifestations nor disease activity parameters (ESR and CRP) showed any significant differences regarding <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity. There was a significant difference between IgM and IgG <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity and cats in the household (12 (80.0%) versus 12 (46.3%), <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02 and 34 (59.6) versus 9 (36.0%), <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04, respectively), as illustrated in <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>.</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">The relationship between <span class="elsevierStyleItalic">Toxoplasma</span> infection and ARDs has been investigated in different studies with debatable results; anti <span class="elsevierStyleItalic">Toxoplasma</span> IgG seropositivity has shown an association with RA and SSc in European patients; however, Latin American patients lacked this relationship.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">17</span></a> Contrastingly, other studies remarked the protective effect exerted by parasitic infections against ARDs.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In this study, both anti-<span class="elsevierStyleItalic">Toxoplasma</span> IgM and IgG antibodies in ARD patients were found to be higher than healthy controls (18.3%, 69.5%, and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.017, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>0.001, respectively), supported by the study done by other studies.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">19,20</span></a> Here, the highest prevalence of anti-<span class="elsevierStyleItalic">Toxoplasma</span> IgG antibodies was reported in RA followed by SLE, then SSc patients (79.5%, 64.3%, 40.0%, and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.038 respectively), consistent with Fischer and colleagues<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">21</span></a> who documented a higher prevalence of anti-<span class="elsevierStyleItalic">Toxoplasma</span> IgG in RA compared to SLE patients. IgM <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity among SLE patients was revealed to have significant difference in comparison to the control group, consistent with the study done by Wilcox, and colleagues.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">22</span></a> Also, a significant difference of IgG <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity was demonstrated in both RA and SLE patients versus the control group. In agreement with that, an association of IgG <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity among RA and SLE was reported regarding latent toxoplasmosis.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">23</span></a> Of note, 13 patients and 3 controls were found to have both types of antibodies. While such cases are commonly described as having reactivation of chronic toxoplasmosis, Dhakal and colleagues<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">24</span></a> concluded that IgM may persist in the patients’ sera for years, hence, chronic cases may be misdiagnosed as having reactivation. Therefore, confirmation of an acute or chronic infection should depend on testing at a reference laboratory.</p><p id="par0090" class="elsevierStylePara elsevierViewall">There was no correlation between <span class="elsevierStyleItalic">T. gondii</span> IgM and IgG seropositivity and disease activity parameters in terms of ESR and CRP in any of the studied diseases. In agreement with these findings, some studies reported no correlation between <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity and ESR or CRP.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">21</span></a> Latent toxoplasmosis with its chronic effects and ARDs with its fluctuating course, necessitate cohort studies on large scales.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Although toxoplasmosis is considered a potential risk factor for ARDs, the specific mechanism of induction or exacerbation is not fully understood. Altered T cell repertoire was reported in RA,<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">25</span></a> and dysregulation of cellular and humoral immune responses was documented in SLE patients as well.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">26</span></a> On the other hand, toxoplasmosis may induce the progression of chronic diseases. Toxoplasmosis promotes IL-17 expression, which contributes to the pathophysiology of several ARDs. <span class="elsevierStyleItalic">Toxoplasma</span> was proved to act as a ligand for Toll-like receptors (TLR); thus, chronic activation of these receptors favors the production of autoantibodies.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">27</span></a> Mimics between SLE activity and manifestations of infection have been observed in many patients causing difficult management of the disease.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Neuro-psychiatric manifestations including lupus-cerebritis and migraine showed significant difference between SLE and controls. SLE is characterized by a wide range of neuro-psychiatric manifestations.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">28</span></a> In RA, neurological affection is multifactorial whether local joint changes, extra-articular rheumatoid nodules, or secondary vasculitis are included. In this study, migraine in SSc and RA patients showed significant difference versus controls. There is an issue of discussion about neuro-psychiatric manifestations in SSc. Noteworthy, some psychiatric disorders like mania and impaired cognitive functions in patients with bipolar disorder were linked to the concentration of <span class="elsevierStyleItalic">Toxoplasma</span> IgM in patients’ sera.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">29</span></a> In agreement with Voss and Stangel,<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">30</span></a> neuro-psychiatric manifestations, particularly lupus-cerebritis and migraine were more prevalent in SLE patients. It was reported that bipolar disorder, obsessive compulsive disorder, attention deficit hyperactivity disorder, anti-social personality disorder, drug abuse, generalized anxiety and panic disorder, autism, schizophrenia, mood disturbances, homicide, and suicide occur more frequently in <span class="elsevierStyleItalic">Toxoplasma</span> infected patients than in normal controls.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">31</span></a> Unfortunately, the development of neuro-toxoplasmosis in SLE patients was found to be usually misdiagnosed as neuro-psychiatric SLE.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">23</span></a> In this study, Neuro-psychiatric manifestations showed non-significant difference in relation to <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity. Many studies were done to explore the role of <span class="elsevierStyleItalic">T. gondii</span> as a potential factor for development of neuro-psychiatric manifestation using serological methods, however debate is still found. Much information is lacking concerning molecular characteristic, pathophysiological, and neurobiological mechanisms of toxoplasmosis.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Among female ARD patients, a significant association between anti-<span class="elsevierStyleItalic">T. gondii</span> IgM seropositivity and history of offspring's fetal congenital anomalies was demonstrated, consistent with a study done on aborted women showed a significant association between toxoplasmosis and RA.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">32</span></a> Children born to mothers suffering from SLE may have neonatal lupus syndrome, including congenital anomalies with a high risk of congenital heart diseases.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">33</span></a> There was non-significant association between <span class="elsevierStyleItalic">T. gondii</span> seropositivity and abortion. A variable range of pregnancy outcomes and subsequent sequelae after birth, including abortion, stillbirth, hydrocephalus, chorioretinitis, cerebral calcification, mental retardation, and learning difficulties, was associated with toxoplasmosis. In addition, a correlation between ARDs with abortion and intrauterine fetal deaths was documented.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">34</span></a> Pregnancy outcome complications were documented in RA patients with disease activity; however, there are debates concerning pregnancy outcomes in SSc patients.</p><p id="par0110" class="elsevierStylePara elsevierViewall">A significant correlation was found between anti-<span class="elsevierStyleItalic">T. gondii</span> IgM, IgG antibodies and cats’ exposure in ARD patients. This factor elucidates the role played by cats as a source of <span class="elsevierStyleItalic">T. gondii</span> transmission in ARD patients. In agreement with these results, Tian et al.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">35</span></a> detected an association between contact with cats and toxoplasmosis prevalence, as well as a significant correlation between <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity and arthritis in China. Neverthless, some studies reported no association between anti-<span class="elsevierStyleItalic">T. gondii</span> antibodies and contact with cat.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">36</span></a> Awareness about the role played by cats in acquisition of toxoplasmosis is important. More efforts are needed to control toxoplasmosis in cat. Also, more accurate studies on larger sample size are valuable.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Interestingly, SSc patients showed no significant link to <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity. Little is known about the link between SSc and <span class="elsevierStyleItalic">Toxoplasma</span>, however, the immune response against chronic toxoplasmosis favoring T helper type (Th) 2 over Th1 response substantiates the hygiene hypothesis, which considers toxoplasmosis and other infections as protective factors against ARDs.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">37</span></a> Conversely, Arnson et al.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">38</span></a> found a positive correlation between SSc and <span class="elsevierStyleItalic">Toxoplasma</span> seroprevalence and concluded that <span class="elsevierStyleItalic">Toxoplasma</span> might play a role in triggering SSc. Molecular mimicry, super-antigen, and endothelial damage were proposed to explain how infections act as triggering cofactors in the immuno-pathogenesis of SSc.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In this study, no significant association was exhibited in <span class="elsevierStyleItalic">T. gondii</span> seropositive ARD patients who received different regimens of medications. The combined pyrimethamine and azithromycin with corticosteroids is recommended regimen for treating ocular toxoplasmosis in immunocompromised patients although there is a leakage in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">39</span></a> Nevertheless, in a murine model of latent toxoplasmosis using ME-49 strain, more <span class="elsevierStyleItalic">T. gondii</span> cysts in the brain and encephalitis were detected when long-term corticosteroid therapy was applied.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">40</span></a> An increased risk of opportunistic infections among treated patients with immunosuppressive drugs as bDMARDs was documented and probably may lead to life-threatening toxoplasmosis.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">41</span></a> The risk of reactivation of latent toxoplasmosis in patients receiving immunosuppressive medications promotes question. A limitation of this study is that the sample size is small with only one patient received bDMARDs. Also, the study is of cross-sectional nature, however, it is not fully granted that randomized controlled trial could be done to assess the impact of toxoplasmosis on ARDs. Also, because of active disease and/or the existence of antiphospholipid antibodies, SLE patients have more abortions than healthy controls, these aspects were not fulfilled.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusion</span><p id="par0125" class="elsevierStylePara elsevierViewall">Toxoplasmosis has shown a diverse relationship with ARDs in different studies. This study highlighted the association between IgM <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity and SLE, and between <span class="elsevierStyleItalic">T. gondii</span> IgG seropositivity and both RA and SLE. Nevertheless, <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity had no association with SSc patients. A significant association was demonstrated between anti-<span class="elsevierStyleItalic">T. gondii</span> IgM seropositivity and history of offspring's fetal congenital anomalies. Besides, cats’ exposure in ARD patients might be a risk factor in toxoplasmosis. Randomized controlled trial with large number of patients is a necessity to explore the actual impact of toxoplasmosis on ARDs whether hazardous or protective.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authors’ contributions</span><p id="par0130" class="elsevierStylePara elsevierViewall">Wafaa A. Aboukamar involved in conceptualization, methodology, software, writing manuscript, data curation, and reviewing manuscript. Samar Habib involved in conceptualization, writing manuscript, and reviewing manuscript. Samar Tharwat and Mohamed Kamal Nassar involved in conceptualization, collection of data, and writing manuscript. Manal A. Elzoheiry involved in laboratory investigation and revising manuscript. Rania Atef involved in collection of data. Manar S. Elmehankar involved in laboratory investigation, reviewing manuscript.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical approval</span><p id="par0135" class="elsevierStylePara elsevierViewall">The study was approved by Mansoura Faculty of Medicine-Institutional Review Board (MFM-IRB) with a code number of R/20.11.1095.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Consent</span><p id="par0140" class="elsevierStylePara elsevierViewall">The study was explained to all participants, and written informed consent was signed by all of them.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Data availability statement</span><p id="par0145" class="elsevierStylePara elsevierViewall">Data would be made available on reasonable request.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0150" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interests</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:17 [ 0 => array:3 [ "identificador" => "xres1995082" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1711887" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1995083" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Propósito" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1711888" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patients’ demographic, clinical and therapeutic data" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Disease activity scores" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Toxoplasmosis risk factors" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Sampling and laboratory tests" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Ethical approval" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Consent" ] 12 => array:2 [ "identificador" => "sec0075" "titulo" => "Data availability statement" ] 13 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 14 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interests" ] 15 => array:2 [ "identificador" => "xack697918" "titulo" => "Acknowledgements" ] 16 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-10-28" "fechaAceptado" => "2023-03-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1711887" "palabras" => array:6 [ 0 => "Autoimmune rheumatic diseases" 1 => "<span class="elsevierStyleItalic">Toxoplasma gondii</span>" 2 => "IgG antibody" 3 => "IgM antibody" 4 => "Seroprevalence" 5 => "ELISA" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1711888" "palabras" => array:6 [ 0 => "Enfermedades reumáticas autoinmunes" 1 => "<span class="elsevierStyleItalic">Toxoplasma gondii</span>" 2 => "Anticuerpo IgG" 3 => "Anticuerpo IgM" 4 => "Seroprevalencia" 5 => "ELISA" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To explore the association between <span class="elsevierStyleItalic">T. gondii</span> and autoimmune rheumatic diseases (ARDs).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This study involved 82 patients with ARDs: 44 rheumatoid arthritis (RA), 28 systemic lupus erythematosus (SLE), and 10 systemic sclerosis (SSc) and 61 age- and sex-matched controls. Sociodemographic, clinical, and laboratory data were collected, and disease activity was assessed. Exposure to toxoplasmosis risk factors was investigated. Serological tests for anti-<span class="elsevierStyleItalic">Toxoplasma</span> IgM and IgG antibodies were assessed using ELISA.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In SLE patients, a significant difference of <span class="elsevierStyleItalic">T. gondii</span> IgM versus controls was detected (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03). In RA and SLE patients, <span class="elsevierStyleItalic">T. gondii</span> IgG showed a significant difference versus controls (34 (77.3%) <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.001 and 18 (64.3%) <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03, respectively). There was no significant difference in SSc versus controls. Fetal congenital anomalies displayed a significant difference in IgM seropositive compared to seronegative patients (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.04). Cat exposure showed a significant difference between IgM and IgG seropositive versus seronegative patients (12 (80.0%) <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.02 and 34 (59.6) <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.04, respectively). There was no significant difference in seropositive patients regarding history of abortion, neuro-psychiatric manifestations, disease activity parameters (ESR, CRP), or different regimens of medications.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Toxoplasma</span> IgM seropositivity is associated with SLE patients. <span class="elsevierStyleItalic">T. gondii</span> IgG seropositivity is associated with both RA and SLE patients. However, <span class="elsevierStyleItalic">Toxoplasma</span> seropositivity had no association with SSc patients. An association between fetal congenital anomalies and IgM seropositivity was demonstrated. A linkage between cat exposure as a risk factor and toxoplasmosis was suggested among ARD patiants. Exploration of impact of toxoplasmosis on ARDs is a necessity through randomized controlled trials.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Purpose" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Propósito</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Explorar la asociación entre <span class="elsevierStyleItalic">Toxoplasma gondii</span> y enfermedades reumáticas autoinmunes (ERA).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Este estudio involucró a 82 pacientes con ERA: 44 con artritis reumatoide (AR), 28 con lupus eritematoso sistémico (LES) y 10 con esclerosis sistémica (SSc); y 61 controles emparejados por edad y sexo. Se recopilaron datos sociodemográficos, clínicos y de laboratorio, y se evaluó la actividad de la enfermedad. Se indagó exposición a factores de riesgo de toxoplasmosis. Las pruebas serológicas de anticuerpos IgM e IgG antitoxoplasma se evaluaron mediante ELISA.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En pacientes con LES se detectó una diferencia significativa de <span class="elsevierStyleItalic">T. gondii</span> IgM vs. controles (p = 0,03). En pacientes con AR y LES, <span class="elsevierStyleItalic">T. gondii</span> IgG mostró una diferencia significativa frente a los controles (34 [77,3%] p = 0,001 y 18 [64,3%] p = 0,03, respectivamente). No hay diferencia significativa en SSc vs. controles. Las anomalías congénitas fetales mostraron una diferencia significativa en los pacientes seropositivos para IgM en comparación con los pacientes seronegativos (p = 0,04). La exposición a los gatos mostró una diferencia significativa entre los pacientes seropositivos para IgM e IgG frente a los seronegativos (12 [80%] p = 0,02 y 34 [59,6] p = 0,04, respectivamente). No hubo diferencias significativas en pacientes seropositivos con respecto a antecedentes de aborto, manifestaciones neuropsiquiátricas, parámetros de actividad de la enfermedad (ESR, CRP) o diferentes regímenes de medicamentos.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La seropositividad a toxoplasma IgM se asocia con pacientes con LES. La seropositividad de IgG frente a <span class="elsevierStyleItalic">T. gondii</span> se asocia tanto con pacientes con AR como con LES. Sin embargo, la seropositividad a toxoplasma no tuvo asociación con pacientes con SSc. Se demostró una asociación entre anomalías congénitas fetales y seropositividad a IgM. Se sugirió un vínculo entre la exposición a los gatos como factor de riesgo y la toxoplasmosis entre los pacientes con ERA. La exploración del impacto de la toxoplasmosis en las ERA es una necesidad a través de ensayos controlados aleatorios.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Propósito" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ARD patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>82) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthy controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>61) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age/year</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.43<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.56<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">†</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.18<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><40 y<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (56.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (63.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.271 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>>40 y<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 (43.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (36.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Sex</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (8.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (14.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.243 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 (91.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (85.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Occupation</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Employed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 (74.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (65.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.252 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Non employed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (25.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (34.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Residence</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rural \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 (72) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (63.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.307 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Urban \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (36.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Socioeconomic status</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Low \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (53.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (65.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.267 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (45.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (34.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Neuro-psychiatric manifestations</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (31.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤0.001<a class="elsevierStyleCrossRef" href="#tblfn0020">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">ESR mm/h</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">§</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (5–100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (3–13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤0.001<a class="elsevierStyleCrossRef" href="#tblfn0020">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">CRP, mg/l</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">§</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5 (2–96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (1–6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤0.001<a class="elsevierStyleCrossRef" href="#tblfn0020">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Medication</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Corticosteroid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 (62.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>csDMARDs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MMF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (11.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>bDMARDs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Cats in the household</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 (52.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (37.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.080 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Raw milk products consumption</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">‡</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 (68.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (45.9) \t\t\t\t\t\t