Potential antitumor effects of short-chain fatty acids in breast cancer models.

The effects of short-chain fatty acids (SCFAs) have been explored against cancer due to the crosstalk between gut microbiota alterations and the immune system as a crucial role in cancer development. We evaluated the SCFAs effects in both in vitro and in vivo breast cancer models. In vitro, the SCFAs displayed contrasting effects on viability index, according to the evaluation of breast cancer cells with different phenotypes, human MCF-7, SK-BR-3, MDA-MD-231, or the mouse 4T1 lineage. Acetate displayed minimal effects at concentrations up to 100 mM. Alternatively, propionate increases or reduces cell viability depending on the concentration. Butyrate and valerate showed consistent time- and concentration-dependent effects on the viability of human or mouse breast cancer cells. The selective FFA2 4-CMTB or FFA3 AR420626 receptor agonists failed to overtake the SCFA actions, except by modest inhibitory effects on MDA-MB-231 and 4T1 cell viability. The FFA2 CATPB or FFA3 and ß-hydroxybutyrate receptor antagonists lacked significant activity on human cell lines, although CATPB reduced 4T1 cell viability. Butyrate significantly affected cell morphology, clonogenicity, and migration, according to the evaluation of MDA-MB-231 and 4T1 cells. A preliminary examination of in vivo oral effects of butyrate, propionate, or valerate, dosed in prophylactic or therapeutic regimens, on several parameters evaluated in an orthotopic breast cancer model showed a reduction of lung metastasis in post-tumor induction butyrate-treated mice. Overall, the present results indicate that in vitro effects of SCFAs did not rely on FFA2 or FFA3 receptor activation, and they were not mirrored in vivo, at least at the tested conditions. Overall, the present results indicate potential in vitro inhibitory effects of SCFAs in breast cancer, independent of FFA2 or FFA3 receptor activation, and, in the metastatic breast cancer model, the butyrate-dosed therapeutic regimen reduced the number of lung metastases.

Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

Effects of boric acid on alveolar sockets filling after dental extraction in rats.

PURPOSE: After extraction, dental alveolus filling aims to reduce bone loss and maintain the alveolus volume during patient rehabilitation. Boric acid (BA) is a boron-derived compound with osteogenic properties and an interesting candidate for alveoli filling. This study aims to investigate the osteogenic capacity of the local application of BA in dental socket preservation. METHODS: Thirty-two male Wistar rats were submitted to upper right incisor extraction and randomly divided into four groups (n = 8): control group (no intervention), BA (8 mg/kg) socket filling, bone graft (Cerabone®, Botiss, Germany), and BA + bone graft socket filling. Animals were euthanized 28 days after dental extraction. MicroCT and histological analysis were performed to evaluate the newly formed bone on the dental alveolus. RESULTS: MicroCT analysis demonstrated that bone volume fraction (BV/TV), bone surface (BS), bone surface/bone volume ratio (BS/BV), bone surface density (BS/TV), trabecular thickness (Tb.Th), total bone porosity (Po-tot), and total volume of pore space (Po.V(tot)) from BA and BA + bone graft rats were significantly different from the control group. Histological evaluation displayed a delayed bone repair in BA rats, with the presence of connective tissue and inflammatory infiltrate. However, the BA + bone graft group demonstrated histological aspects like the bone graft animals, with less organized osteoblasts, suggesting inferior bone repair. CONCLUSION: Osteogenic capacity did not depend on the BA local application after 28 days of dental extraction. The presence of inflammation in the BA group can represent toxicity induced by the substance dosage used.

Clinical characterisation of a multicentre nationwide cohort of patients with antisynthetase syndrome.

BACKGROUND: Antisynthetase syndrome (ASyS) is characterised by the association of inflammatory myopathy, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon (RP) or mechanic's hands (MH), with the presence of anti-aminoacyl-tRNA-synthetase antibodies (anti-ARS). It has been suggested that different anti-ARS may be associated with distinct clinical pictures. OBJECTIVE: To characterise the clinical and immunological features of a multicentric nationwide cohort of ASyS patients. METHODS: This is a multicentre retrospective cohort study including patients with ASyS from nine Portuguese rheumatology centres. Data on patients' demographics, signs and symptoms, laboratory results, pulmonary imaging findings and treatment with immunomodulators were collected. Comparison between patients with different anti-ARS antibodies was made using the Chi-square test for categorical variables and Student's t-test or Man-Whitney test for continuous variables, considering anti-Jo1 positive patients as the reference group. RESULTS: Seventy patients were included (70% female) with a median age in years at disease onset of 52 (15-75) years and median follow-up time of 3 years (range 0-32). The three most common clinical manifestations were ILD (n=53, 75.7%), followed by arthritis (n=43, 61.4%) and myositis (n=37, 52.9%). Forty-three patients were positive for anti-Jo1 (61.4%), 11 for anti-PL12 (15.7%), 10 for anti-PL7 (14.3%), 4 for anti-EJ (5.7%), and 2 for anti-OJ (2.9%) antibodies. Antibody co-positivity with anti-Ro52 antibodies was found in 15 patients (21.4%) and was more prevalent in anti-Jo1 patients. ILD prevalence was similar in the different anti-ARS subgroups, without statistically significant differences. Patients positive for anti-PL7 antibodies had significantly lower risk of presenting arthritis (p =< 0.05) and those positive for anti-PL-12 antibodies had a significantly lower risk of presenting myositis than the reference group of anti-Jo1 positive patients (p =< 0.05). RP was more frequently found in patients positive for anti-PL-12 than in anti-Jo1-positive patients (p =< 0.05). Malignancies were reported in four (5.7%) patients, none of whom were anti-Ro52-positive, and one of such patients had a double malignancy. Only three deaths were reported. Corticosteroids were the most frequently prescribed therapy and the use of immunosuppressive drugs was decided according to the type of predominant clinical manifestation. CONCLUSION: The three most common clinical manifestations were ILD, followed by arthritis and myositis. Patients positive for anti-PL7 antibodies had significantly lower risk of presenting arthritis and those positive for anti-PL-12 antibodies had a significantly lower risk of presenting myositis than the reference group of anti-Jo1 positive patients. RP was more frequently found in patients positive for anti-PL-12 than in anti-Jo1-positive patients. Corticosteroids were the most frequently prescribed therapy. These results are generally concordant with data retrieved from international cohorts.

Relações sociais e direitos na narrativa de adolescentes em cumprimento de medida socioeducativa / Social relations and rights in the narrative of teenagers in compliance with socio-educational measures / Relaciones sociales y derechos en la narrativa de adolescentes en cumplimiento de medidas socioeducativas

O artigo discute as relações intersubjetivas que atuam na vida de jovens em conflito com a lei e como tais relações os constituem como sujeitos de direitos. O ponto de partida foi a escuta compreensiva dos próprios adolescentes, em uma pesquisa qualitativa, realizada com jovens em regime de privação de liberdade. Tomou-se como objeto de pesquisa o processo de elaboração de uma obra escrita e ilustrada por adolescentes que cumprem medida socioeducativa. A pesquisa foi baseada em redações elaboradas por eles, no contexto do 4º Concurso de Redação da Defensoria Pública da União (DPU). Situações de violação de direitos foram identificadas no discurso dos sujeitos, organizadas em núcleos de significado da linguagem e discutidas à luz da Psicologia Histórico-cultural, estabelecendo-se um diálogo com Le Breton, Vigotski e autores que discutem vulnerabilidades e socioeducação.

The article discusses the intersubjective relationships that play in the lives of young people in conflict with the law and how such relationships constitute them as subjects of rights. The starting point was the comprehensive listening of the adolescents themselves, in a qualitative research, carried out with young people in a regime of deprivation of liberty. For this, the research object was the process of elaboration of a work written and illustrated by adolescents who fulfill a socio-educational measure, which was based on essays prepared by them, in the context of the 4th Essay Contest of the Public Defender's Office of the Union (DPU). Situations of violence and violation of rights, were identified in the subjects' discourse, organized into language meaning cores and discussed in the light of Socio-historical Psychology, establishing a dialogue with Le Breton, Vigotski and authors who discuss vulnerabilities and socio-education.

El artículo discute las relaciones intersubjetivas que actúan en la vida de los jóvenes en conflicto con la ley y cómo dichas relaciones los convierten en sujetos de derecho. El punto de partida fue la escucha integral de los propios adolescentes, en una investigación cualitativa, realizada con jóvenes en régimen de privación de libertad. Para ello, el objeto de investigación fue el proceso de elaboración de una obra escrita e ilustrada por adolescentes que cumplen una medida socioeducativa, la cual se basó en ensayos elaborados por ellos, en el marco del 4° Concurso de Ensayo de la Defensoría Pública de Unión (UPD). Fueron identificadas situaciones de violencia y violación de derechos en el discurso de los sujetos, organizadas en núcleos de sentido del lenguaje y discutidas a la luz de la Psicología Sociohistórica, entablando un diálogo con Le Breton, Vigotski y autores que discuten vulnerabilidades y socioeducación.

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.

Central and peripheral effects of environmental enrichment in a mouse model of arthritis.

This study analyzed whether environmental enrichment (EE) modulates the nociceptive and inflammatory responses in the mouse model of arthritis induced by Complete Freund's Adjuvant (CFA). Ninety male mice (C57BL/6-JUnib, 4-weeks-old; 20-25 g) were distributed into EE and standard (SE) groups. For EE, mice were kept in bigger cages using an alternation of materials to chew (wood and paper), for nesting (cotton), to use as hiding places (plastic tunnels), and for voluntary exercise (wheel running). Arthritis was induced by an injection of CFA (50 µL) into the right hind paw or saline solution in the control group. Separate groups received the anti-inflammatory drug dexamethasone (0.5 mg/kg; every 48 h). Inflammatory and pain measurements were performed from 1 to 35 days after CFA administration. EE per se reduced the acute paw edema formation and arthritis scores. The serum levels of tumor necrosis factor (TNF) were undetectable in any experimental groups. EE diminished the immunopositivity for the microglia marker IBA1 in the pre-frontal cortex, with slight changes for hippocampal GFAP-positive activated astrocytes. Finally, EE induced a marked increment of brain-derived nerve factor (BDNF) expression in the hippocampus, an effect that was fully prevented by dexamethasone. These data bring novel evidence on the peripheral and central effects of EE in a mouse arthritis model.

Gender differences in clinical features and outcomes of a Portuguese systemic sclerosis cohort.

Evidence for the role of sex in the clinical manifestations of systemic sclerosis (SSc) patients is emerging. Some multicenter cohorts have shown that male SSc patients have more severe disease and worse survival. To assess the differences in clinical manifestations and survival in Portuguese SSc patients according to gender. Data from male and female adult SSc patients included in the Rheumatic Diseases Portuguese Register (Reuma.pt) were analysed and compared. Survival was calculated for patients included in Reuma.pt. within the first two years of diagnosis (inception cohort). In total, 1054 adult patients with SSc were included, 12.5% males. No differences in demographic features and comorbidities were found between the sexes, except for a higher rate of cigarette smokers among men. Diffuse cutaneous SSc and anti-topoisomerase antibodies were more prevalent in males than females. Additionally, male patients presented significantly more myositis, interstitial lung disease and gastric involvement. There were no differences in the patterns of drug use between the sexes. During follow-up, more deaths were reported in men than women (12.1% vs 7.3%, p = 0.04). The overall 1-, 3-, and 5-year survivals from diagnosis of the inception cohort (N = 469) for men vs women were 96.4% vs 98.2%, 93% vs 95.9%, and 75.8% vs 93.2%, respectively, with statistically significant differences (p < 0.01). This study confirms the existence of gender differences in clinical and immunological SSc features. Although SSc is less common in men than women, men have a more severe expression of skin and internal organ involvement and worse survival. Key Points • There are differences in SSc disease manifestations between sexes. • Males more commonly have diffuse cutaneous SSc, anti-topoisomerase antibodies, pulmonary and musculoskeletal involvement. • In the inception cohort, men had worse survival rates than women.

Synthesis, Characterization, Antiproliferative Activity of Galloyl Derivatives and Investigation of Cytotoxic Properties in HepG2/C3A Cells.

BACKGROUND: Appropriate substituents in the galloyl group could lead to significant biological properties. OBJECTIVES: Novel galloyl-substituted compounds bearing 2-substituted-1, 3, 4-oxadiazol-5-yl, 5- substituted-1,2,4-triazol-3-yl, and carboxamide groups were synthesized and evaluated for their antiproliferative activity. Additionally, galloyl hydrazide (2) was evaluated by performing cytotoxicity, membrane integrity, cell cycle, and apoptosis assays in HepG2/C3A cells. METHODS: General procedure was used for the synthesis of galloyl-substituted (3-9, 11) and characterized by their spectroscopic data (1H and 13C NMR). The antiproliferative activity of all novel galloyl derivatives was evaluated against nine human tumors and one nontumoral cell line. Three response parameters (GI50, TGI, and LC50) were calculated. The cytotoxicity test was performed for the resazurin assay. The membrane integrity, cell cycle, and apoptosis assays were performed by flow cytometry. RESULTS: The substitution of the methoxy group of the galloyl ring system for a carboxamide group (3, 4, 5, and 6) produced compounds with moderate antitumoral activity, particularly 6, against six human cancer cell lines, K-562, PC-3, NCI-ADR/RES, OVCAR, 786-0 and NCI-H460, with GI50 values ≤ 9.45 µg/mL. Triazole derivatives 7 and 8 exhibited higher antitumoral activity toward OVCAR, MCF-7 and leukemia K-562 cell lines, exhibiting GI50 values less than 10 µg/mL. Compound 11 displayed significant activity against PC-3 (GI50 = 4.31 µg/mL), OVCAR (GI50 = 8.84 µg/mL) and K-562 (GI50 = 8.80 µg/mL) cell lines. Galloyl hydrazide (2) had cytotoxic activity in HepG2/C3A cells (IC50 = 153.7 µg/mL). In membrane permeability, cell count, cell cycle, and apoptosis assays, as determined using the IC50 of compound (2) in HepG2/C3A cells, increased membrane permeability, decreased cell count, altered cell cycle, and initial apoptosis was observed compared to the control group. CONCLUSION: Thus, our results showed for the first time the synthesis, antiproliferative activity, and cytotoxicity of galloyl-substituted compounds. Galloyl-substitution does not have a very strong synergistic effect in the inhibition of cancer cell proliferation compared with galloyl hydrazide (2). Compound 2 demonstrated promising activity in HepG2/C3A hepatocarcinoma cells.

Psychological symptoms and salivary inflammatory biomarkers in patients with dentofacial deformities: a case-control study.

Individuals with dentofacial deformities often display a low quality of life (QoL) through biological mechanisms that remain unraveled. In this case-control study, the salivary levels of cytokines, glutamate, and kynurenine metabolites were assessed in patients undergoing orthognathic surgery (OS), while correlating these parameters with QoL and psychological symptoms. Thirty-six patients were enrolled in control (under orthodontic treatment) and test (undergoing OS) groups, matched by age and sex. The QoL was assessed through the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Orthognathic Quality of Life Questionnaire (OQLQ). The psychological symptoms were evaluated by the Satisfaction with Life Scale, the Rosenberg Self-Esteem Scale (RSES), and the Depression, Anxiety, and Stress Scale-21 (DASS-21). The salivary levels of IL-1ß, IL-6, IL-10, glutamate, and kynurenine metabolites were evaluated. The OQLQ demonstrated increased QoL scores in the test group, regarding social aspects, facial esthetics, and function domains, without significant differences in respect to the other surveys. These patients displayed higher IL-1ß and glutamate levels; conversely, the kynurenine metabolites were unaltered. The glutamate levels positively correlated with the OQLQ function scores. The data brings novel evidence about the psychobiological features of patients with dentofacial deformities, showing salivary variations of inflammatory biomarkers in these individuals.

Targeting thymidine phosphorylase inhibition in human colorectal cancer xenografts.

Human thymidine phosphorylase (hTP) is overexpressed in several solid tumors and is commonly associated with aggressiveness and unfavorable prognosis. 6-(((1,3-Dihydroxypropan-2-yl)amino)methyl)-5-iodopyrimidine-2,4(1H,3H)-dione (CPBMF-223) is a noncompetitive hTP inhibitor, which has been described as a tumor angiogenesis inhibitor. The present study investigated the effects of CPBMF-223 in a xenograft tumor induced by human colorectal carcinoma cells (HCT-116). Additionally, CPBMF-223 capacity to reduce cell migration, its toxicological profile, and pharmacokinetic characteristics, were also evaluated. The intraperitoneal treatment with CPBMF-223 markedly prevented the relative tumor growth with an efficacy similar to that observed for 5-fluorouracil. Interestingly, number of vessels were significantly decreased in the treated groups. Moreover, CPBMF-223 significantly reduced the migration of cell line HCT-116. In the Ames assay and in an acute oral toxicity test, the molecule did not alter any evaluated parameter. Using the zebrafish toxicity model, cardiac and locomotor parameters were slightly changed. Regarding the pharmacokinetics profile, CPBMF-223 showed clearance of 9.42 L/h/kg after intravenous administration, oral bioavailability of 13.5%, and a half-life of 0.75 h. Our findings shed new light on the role of hTP in colorectal cancer induced by HCT-116 cell in mice, pointing out CPBMF-223 as, hopefully, a promising drug candidate.

Understanding the appetite modulation pathways: The role of the FFA1 and FFA4 receptors.

Pharmaconutrition is an area of current interest, especially concerning the advances in the pharmacology of nutrient-sensing receptors, as have been accomplished in the last 20 years. The family of free fatty acid (FFA) receptors is composed of four members, sequentially named as FFA1 to FFA4, which are activated by the short to long-chain fatty acids. The affinity of the FFA1 and FFA4 receptors for the omega-3 polyunsaturated fatty acids prompted pre-clinical and clinical investigations regarding their involvement in metabolic diseases. The main studies have been focused on the receptors' expression analyses, the featuring of knockout mice, and the assessment of selective synthetic ligands. These clearly have indicated a relevant role for FFA1 and FFA4 in the peripheral and central circuits for the regulation of energetic metabolism. This review article aimed to discuss the relevance of the FFA1 and FFA4 receptors in appetite-related complications, mainly related to obesity, cancer cachexia, and anorexia in the elderly, emphasizing whether their pharmacological modulation might be useful for the management of these disorders.

Saving more than R$ 85 billion of the Brazilian Social Security System: the case of the PRBI / Economía de más de R$ 85 mil millones en el Régimen General de Previsión Social de Brasil: el caso del PRBI / Economizando mais de R$ 85 bilhões ao Regime Geral de Previdência Social do Brasil: o caso do PRBI

Abstract Since 2016, the number of recipients of incapacity allowance in Brazil has been continuously falling. This article presents the program of incapacity benefits assessment (PRBI) to help understand the dynamics around incapacity allowance and similar benefits. The study shows that the PRBI can save more than R$ 85 billion of the budget allocated to social security in the country.

Resumen El número de beneficiarios de subsidios por incapacidad laboral ha disminuido drásticamente desde 2016. Este artículo muestra que el Programa para la Evaluación de Subsidios por Incapacidad Laboral (PRBI) es clave para entender esta dinámica y es responsable de una economía de más de R$ 85 mil millones para el Régimen General de Previsión Social de Brasil.

Resumo O número de benefícios de auxílio-doença vem caindo drasticamente desde 2016. Este artigo mostra que o Programa de Revisão dos Benefícios por Incapacidade (PRBI) é fundamental para entender essa dinâmica, e estima que o Programa seja responsável por uma economia de mais de R$ 85 bilhões ao Regime Geral de Previdência Social.

Targeting FFA1 and FFA4 receptors in cancer-induced cachexia.

Free fatty acid (FFA) receptors FFA1 and FFA4 are omega-3 molecular targets in metabolic diseases; however, their function in cancer cachexia remains unraveled. We assessed the role of FFA1 and FFA4 receptors in the mouse model of cachexia induced by Lewis lung carcinoma (LLC) cell implantation. Naturally occurring ligands such as α-linolenic acid (ALA) and docosahexaenoic acid (DHA), the synthetic FFA1/FFA4 agonists GW9508 and TUG891, or the selective FFA1 GW1100 or FFA4 AH7614 antagonists were tested. FFA1 and FFA4 expression and other cachexia-related parameters were evaluated. GW9508 and TUG891 decreased tumor weight in LLC-bearing mice. Regarding cachexia-related end points, ALA, DHA, and the preferential FFA1 agonist GW9508 rescued body weight loss. Skeletal muscle mass was reestablished by ALA treatment, but this was not reflected in the fiber cross-sectional areas (CSA) measurement. Otherwise, TUG891, GW1100, or AH7614 reduced the muscle fiber CSA. Treatments with ALA, GW9508, GW1100, or AH7614 restored white adipose tissue (WAT) depletion. As for inflammatory outcomes, ALA improved anemia, whereas GW9508 reduced splenomegaly. Concerning behavioral impairments, ALA and GW9508 rescued locomotor activity, whereas ALA improved motor coordination. Additionally, DHA improved grip strength. Notably, GW9508 restored abnormal brain glucose metabolism in different brain regions. The GW9508 treatment increased leptin levels, without altering uncoupling protein-1 downregulation in visceral fat. LLC-cachectic mice displayed FFA1 upregulation in subcutaneous fat, but not in visceral fat or gastrocnemius muscle, whereas FFA4 was unaltered. Overall, the present study shed new light on FFA1 and FFA4 receptors' role in metabolic disorders, indicating FFA1 receptor agonism as a promising strategy in mitigating cancer cachexia.

Remission and low disease activity matrix tools: results in real-world rheumatoid arthritis patients under anti-TNF therapy.

BACKGROUND: Remission/ low disease activity (LDA) are the main treatment goals in rheumatoid arthritis (RA) patients. Two tools showing the ability to predict golimumab treatment outcomes in patients with RA were published. OBJECTIVES: To estimate the real-world accuracy of two quantitative tools created to predict RA remission and low disease activity. METHODS: Multicenter, observational study, using data from the Rheumatic Diseases Portuguese Register (Reuma.pt), including biologic naïve RA patients who started an anti-TNF as first-line biologic and with at least 6 months of follow-up. The accuracy of two matrices tools was assessed by likelihood-ratios (LR), sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and area under the ROC curve (AUC). RESULTS: 674 RA patients under first-line anti-TNF (266 etanercept, 186 infliximab, 131 adalimumab, 85 golimumab, 6 certolizumab pegol) were included. The median (IQR) age was 53.4 (44.7-61.1) years and the median disease duration was 7.7 (3.7-14.6) years. The majority were female (72%). Most patients were RF and/or ACPA positive (75.5%) and had erosive disease (54.9%); 58.6% had comorbidities. At 6-months, 157 (23.3%) patients achieved remission (DAS28 ESR < 2.6) and 269 (39.9%) LDA (DAS28 ESR ≤ 3.2). Area under the curve for remission in this real-world sample was 0.756 [IC 95% (0.713-0.799)] and for LDA was 0.724 [IC 95% (0.686 -0.763)]. The highest LR (8.23) for remission state was obtained at a cut-off ≥ 67%, with high specificity (SP) (99.6%) but low sensitivity (SN) (3.2%). A better balance of SN and SP (65.6% and 73.9%, respectively) was observed for a cut-off >30%, with a LR of 2.51, PPV of 43.3% and NPV of 87.6%. CONCLUSION: In this population, the accuracy of the prediction tool was good for remission and LDA. Our results corroborate the idea that these matrix tools could be helpful to select patients for anti-TNF therapy.

Osteopoikilosis: case series from Portuguese Rheumatology Centers.

Osteopoikilosis (OPK) is a rare, hereditary, usually asymptomatic disease characterized by the presence of multiple, well-defined sclerotic lesions distributed in peri-articular locations, frequently diagnosed as an incidental finding. Differential diagnosis with osteoblastic metastases is fundamental. This article reports six cases of OPK diagnosed in Portuguese Rheumatology Centers.