Involvement of IL17A and IL17RA variants in interleukin-17A levels and disease activity in ulcerative colitis.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor (IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC.

Potential use of stem cell therapies for treating osteoarthritis and rheumatoid arthritis.

Arthritis, defined as a chronic inflammation often accompanied by swelling of one or more joints, encompasses more than 100 conditions that affect the joints, tissues around them as well as other connective tissues. This condition causes severe discomfort compromising the quality of life drastically, and thereby inflicts severe financial and social impact on the people affected. The incidence rate of arthritis is increasing all around the globe including the United States every year. In general, osteoarthritis (OA) affects more people in comparison to rheumatoid arthritis (RA). In the USA itself, more than 14 million people are affected by OA in comparison to 1.4 million people suffering from RA. In both conditions, elevated levels of proinflammatory cytokines have been recorded, this incidence generally precedes the cartilage degradation observed in the patients. The use of mesenchymal stem cells (MSCs) has proven to be a safe and efficient therapeutic option for treating many inflammation-rooted pathological conditions. Evidence suggests that MSCs down-regulate the effects of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1B, IL-2, and IL-17, and help restore the functions of immune cells. In addition, these cells promote the polarization of M2 phenotype macrophages, thus contributing to the suppression of the inflammatory process and consequentially to cartilage regeneration. Preclinical and clinical trials have proven the safety and effectiveness of this therapy, supported by the fact that these do not provoke any host immune response, and their influence on the cytokine profiles. An attempt to survey the results of stem cell therapy for treating arthritis has been carried out in this review.

The first report of leukocytoclastic vasculitis induced by once-weekly subcutaneous semaglutide.

INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations.

Differences in vocal brain areas and astrocytes between the house wren and the rufous-tailed hummingbird.

The house wren shows complex song, and the rufous-tailed hummingbird has a simple song. The location of vocal brain areas supports the song's complexity; however, these still need to be studied. The astrocytic population in songbirds appears to be associated with change in vocal control nuclei; however, astrocytic distribution and morphology have not been described in these species. Consequently, we compared the distribution and volume of the vocal brain areas: HVC, RA, Area X, and LMAN, cell density, and the morphology of astrocytes in the house wren and the rufous-tailed hummingbird. Individuals of the two species were collected, and their brains were analyzed using serial Nissl- NeuN- and MAP2-stained tissue scanner imaging, followed by 3D reconstructions of the vocal areas; and GFAP and S100ß astrocytes were analyzed in both species. We found that vocal areas were located close to the cerebral midline in the house wren and a more lateralized position in the rufous-tailed hummingbird. The LMAN occupied a larger volume in the rufous-tailed hummingbird, while the RA and HVC were larger in the house wren. While Area X showed higher cell density in the house wren than the rufous-tailed hummingbird, the LMAN showed a higher density in the rufous-tailed hummingbird. In the house wren, GFAP astrocytes in the same bregma where the vocal areas were located were observed at the laminar edge of the pallium (LEP) and in the vascular region, as well as in vocal motor relay regions in the pallidum and mesencephalon. In contrast, GFAP astrocytes were found in LEP, but not in the pallidum and mesencephalon in hummingbirds. Finally, when comparing GFAP astrocytes in the LEP region of both species, house wren astrocytes exhibited significantly more complex morphology than those of the rufous-tailed hummingbird. These findings suggest a difference in the location and cellular density of vocal circuits, as well as morphology of GFAP astrocytes between the house wren and the rufous-tailed hummingbird.

Assessment of radiological hazards from radioactivity natural of cement used in Dwellings in Rio de Janeiro, Brazil.

Brazil is the fourth largest cement consumer in the world and the largest producer in Latin America, around 1.3% of global production. The main inputs in the manufacture of cement are limestone and clay. Few studies have been carried out in the country on the risk of these materials used in civil construction. Therefore, the objective of this present work is to evaluate the radiological danger that they can present to society. Gamma spectrometry analysis on 16 samples of different brands of cement used as construction material in Rio de Janeiro (Brazil) was performed in this study, using an HPGe detector and the Genie 2000 data acquisition software. Samples were set to count for an accumulation time of 14,400 s (4 h) and all measurements were corrected to eliminate background and backscattering. Activity concentrations are determined for 226Ra was from (41.2 ± 1.6 to 174.9 ± 3.9) Bq kg-1, 232Th was from (15.7 ± 0.5 to 43.1 ± 0.7) Bq kg-1 and 40K was from (82.6 ± 7.2 to 254 ± 17) Bq kg-1. To assess radiological health risks: mean values of Radium Activity Equivalent 150.0 ± 3.4 Bq kg-1, Annual Gonadal Dose Equivalent 468 ± 11 µSv year-1 and Lifetime Excess Cancer Risk (ELCR) 2.42 ± 0.06 were calculated. Total Absorbed Dose Rates ranged from 72.2 ± 1.7 to 225.1 ± 5.2 nGy h-1. The damage to collective health was also estimated from the annual effective dose rates with an estimated total cost of damage to health of US$ 130 million. Values are generally within global limits reported by UNSCEAR.

2024 UPDATE: the Brazilian Diabetes Society position on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) in people with prediabetes or type 2 diabetes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world's population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. METHODS: The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. RESULTS AND CONCLUSIONS: The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium-glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.

The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Natural radioactivity in mineral phosphate fertilizers and its impacts on human health: an overview.

Humans are constantly exposed to radioactivity present in rocks, soils, and water, mainly from materials in the Earth's crust that contain chemical elements belonging to the radioactive series of uranium and thorium. An important anthropogenic source of these natural radioisotopes to the environment is fertilizers, widely used to increase agricultural productivity. Exposure to ionizing radiation can become a public health problem worldwide, since it is related to the development of different cancers in humans. The present study aimed to survey research on the radioactive content in different types of mineral phosphate fertilizers used around the world through a comprehensive review of the Scopus and Web of Science databases. About 80 scientific articles fit the purpose of this review. The concentration activity values found varied widely from one country to another, and there is no specific legislation that determines the maximum allowed limits of radioisotopes in these agricultural inputs. In addition, there are still uncertainties regarding the impact of natural radioactivity from fertilizers on human health, highlighting the need for further investigations on the subject.

Comparative effectiveness and cost-effectiveness of cardioprotective glucose-lowering therapies for type 2 diabetes in Brazil: a Bayesian network model.

BACKGROUND: The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. METHODS: We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. RESULTS: In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69-0.96)], GLP-1A [HR: 0.79 (95% CI 0.67-0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59-0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521-10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227-18,121) and Int$29,119 (95% CI: 23,811-35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. CONCLUSIONS: In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. TRIAL REGISTRATION: CRD42020194415.

Therapeutic Efficacy, Radiotoxicity and Abscopal Effect of BNCT at the RA-3 Nuclear Reactor Employing Oligo-Fucoidan and Glutamine as Adjuvants in an Ectopic Colon Cancer Model in Rats.

Boron neutron capture therapy (BNCT) is based on the preferential uptake of 10B compounds by tumors, followed by neutron irradiation. The aim of this study was to assess, in an ectopic colon cancer model, the therapeutic efficacy, radiotoxicity, abscopal effect and systemic immune response associated with (BPA/Borophenylalanine+GB-10/Decahydrodecaborate)-BNCT (Comb-BNCT) alone or in combination with Oligo-Fucoidan (O-Fuco) or Glutamine (GLN), compared to the "standard" BPA-BNCT protocol usually employed in clinical trials. All treatments were carried out at the RA-3 nuclear reactor. Boron biodistribution studies showed therapeutic values above 20 ppm 10B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCT was significantly smaller for all BNCT groups vs. SHAM (p < 0.05). The parameter "incidence of tumors that underwent a reduction to ≤50% of initial tumor volume" exhibited values of 62% for Comb-BNCT alone, 82% for Comb-BNCT+GLN, 73% for Comb-BNCT+O-Fuco and only 30% for BPA-BNCT. For BPA-BNCT, the incidence of severe dermatitis was 100%, whereas it was significantly below 70% (p ≤ 0.05) for Comb-BNCT, Comb-BNCT+O-Fuco and Comb-BNCT+GLN. Considering tumors outside the treatment area, 77% of Comb-BNCT animals had a tumor volume lower than 50 mm3 vs. 30% for SHAM (p ≤ 0.005), suggesting an abscopal effect of Comb-BNCT. Inhibition of metastatic spread to lymph nodes was observed in all Comb-BNCT groups. Considering systemic aspects, CD8+ was elevated for Comb-BNCT+GLN vs. SHAM (p ≤ 0.01), and NK was elevated for Comb-BNCT vs. SHAM (p ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reduced radiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect.

Co-application of citric acid and Nocardiopsis sp. strain RA07 enhances phytoremediation potentiality of Sorghum bicolor L.

This study investigated the combined effects of citric acid (CA) and Nocardiopsis sp. RA07 on the phytoremediation potential of lead (Pb)- and copper (Cu)-contaminated soils by Sorghum bicolor L. The strain RA07 was able to tolerate Pb and Cu, and exhibited plant growth-promoting features like siderophore production, indole-3-acetic acid (IAA) synthesis, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity and phosphate solubilization. The combined application of CA and strain RA07 significantly increased S. bicolor growth, chlorophyll content and antioxidant enzymatic activity, and decreased oxidative stress (hydrogen peroxide and malondialdehyde content) under Pb and Cu stress circumstances as compared to individual treatments (i.e., CA and strain RA07). Furthermore, the combined application of CA and RA07 significantly enhanced S. bicolor ability to accumulate Pb and Cu by 64.41% and 60.71% in the root and 188.39% and 125.56% in the shoot, respectively, as compared to the corresponding uninoculated plants. Our results indicate that inoculation of Nocardiopsis sp. together with CA could be a useful practical approach to mitigate Pb and Cu stress on plant growth and increase the effectiveness of phytoremediation in Pb- and Cu-polluted soils.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection.

The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD.

How are rheumatologists from Argentina managing patients with arthralgias suspicious for progressing to rheumatoid arthritis?

Patients with arthralgias who could be at risk of progressing to rheumatoid arthritis (RA) represent a clinical challenge. Recommendations for their management and treatment are lacking. The purpose of the present study was to determine how Argentinean rheumatologists deal with these patients. We developed an anonymous ad hoc survey which was sent to 522 Argentinean rheumatologists. The RA study group of our Argentinean Rheumatology National Society assisted in forwarding the surveys to its members via the internet (e-mail or WhatsApp). The findings of the collected data are presented as descriptive statistics. The questionnaires were completed by 255 rheumatologists (overall response rate of 48.9%), and 97.6% confirmed that their practices had received medical consultations to rule out RA in patients with arthralgias. Ultrasound (US) was the method of first choice (93.7%) as part of the evaluation of these patients. For those in whom US power Doppler signal was present in at least one joint, 93.7% of the participants would start treatment and methotrexate was the first choice (58.1%). In patients with tenosynovitis but no synovitis on US, most rheumatologists would start treatment (89.4%), being NSAIDs the drug of first choice (52.3%). Argentinean rheumatologists evaluate patients with imminent RA and treat them based on their clinical judgment and findings from the US evaluation of affected joints; the drug of first choice for these patients among these rheumatologists was methotrexate. Despite published data of recent clinical trials, recommendations for the management and treatment of these patients are necessary.

Blockage of the IL-31 Pathway as a Potential Target Therapy for Atopic Dermatitis.

Atopic dermatitis (AD), a pruritic, inflammatory chronic disease with multifactorial pathogenesis, has been a therapeutic challenge. Novel target treatments aim to reduce not only the immunologic dysfunction and microbiome dysbiosis but also the recovery of the damaged skin barrier. The current review focuses on the interleukin 31 (IL-31) pathway and AD and offers an overview of the current clinical studies with monoclonal antibodies blocking this cascade. Pruritus, the key symptom of AD, has substantial participation of the IL-31 complex and activation of relevant signaling pathways. Epidermal keratinocytes, inflammatory cells, and cutaneous peripheral nerves express the interleukin-31 receptor α-chain (IL-31RA), upregulated by Staphylococcus aureus toxins or Th2 cytokines involved in AD. Nemolizumab is a humanized monoclonal antibody that antagonizes IL-31RA, inhibiting the IL-31 cascade and therefore contributing to reducing the pruritus and inflammation and recovering the damaged skin barrier in AD patients. Phases 2 and 3 clinical trials with nemolizumab in AD show a suitable safety profile, with a fast, efficient, and sustained reduction of pruritus and severity scores, especially when associated with topical treatment. Deciphering the full interplay of the IL-31 pathway and AD may expand the potential of nemolizumab as a targeted therapy for AD and other pruritic conditions.

Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE.

OBJECTIVES: Evaluate the importance of treatment sequencing in SELECT-COMPARE, assessing potential differences between starting upadacitinib or adalimumab therapy following inadequate MTX response. METHODS: Patients from SELECT-COMPARE were randomized to upadacitinib 15 mg once daily, placebo or adalimumab 40 mg. Per protocol, patients with <20% improvement in tender or swollen joint counts (weeks 14, 18, 22) or failure to achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) at week 26 were blindly switched from upadacitinib to adalimumab or vice versa. Treatment outcomes, including clinical remission/LDA, physical function, pain and a novel combined endpoint for deep response, were evaluated through 48 weeks and corresponding time-averaged response rates determined. Data were analysed by initial randomized group regardless of any subsequent switch in therapy. RESULTS: This post hoc analysis included 651 patients initially randomized to upadacitinib (of whom 252 switched to adalimumab) and 327 patients initially randomized to adalimumab (of whom 159 switched to upadacitinib). At week 48, patients randomized to either therapy demonstrated similar achievement of most treatment endpoints. Greater improvements in the total time spent in a lower disease state were observed for initial upadacitinib vs initial adalimumab therapy across most clinical and patient-reported outcomes through 48 weeks, and the median time to DAS28(CRP) <2.6/≤3.2 occurred 6-8 weeks earlier among those randomized to upadacitinib. CONCLUSION: Following a modified treat-to-target strategy, rates of CDAI remission/LDA and DAS28(CRP) <2.6/≤3.2 at 48 weeks were similar, regardless of starting therapy. However, patients initially receiving upadacitinib reached treatment targets more quickly and spent more time in clinical targets over the initial 48 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02629159.

Productive diagnosis offrog culture in the state of Rio de Janeiro / Diagnóstico produtivo da ranicultura no estado do Rio de Janeiro

Brazilian frog farming has a history of production that began in the state of Rio de Janeiro in 1935. Over the years, this activity has spread throughout Brazil, with technological advances that have improved the productivity and health of enterprises. However, structuring the production chain has presented moments of growth and decline, culminating in low production compared with other aquaculture activities. Despite efforts focused on restructuring the chain, data on enterprises and their actors remain scarce. To obtain information on the current scenario of frog farming in the state of Rio de Janeiro, in this study, an online survey of data on frog producers in Rio de Janeiro was conducted. In general, frog farming in Rio de Janeiro has not shown substantial improvements in terms of structuring. Its dynamics are still linked to lowproduction, family run enterprises, little insertion into the market, and not being formalized, encompassing aspects related to fiscal, environmental, and health issues. Therefore, the restructuring process of the frog chain in the state depends on overcoming the bottlenecks mentioned in this study. These predominantly refer to the availability of information on the relevant aspects of management and regularization of production.(AU)

A ranicultura brasileira apresenta um histórico de produção que se iniciou no estado do Rio de Janeiro em 1935. Com o passar dos anos essa atividade se difundiu para todo o Brasil, apresentando avanços tecnológicos que melhoraram o manejo sanitário e a produtividade dos empreendimentos. Contudo, a estruturação da cadeia produtiva apresentou momentos de crescimento e declínio, culminando com uma baixa produção em comparação com outras atividades aquícolas. Apesar dos esforços focados na reestruturação da cadeia, ainda são escassos dados sobre os empreendimentos e seus atores. Com o objetivo de obter informações acerca do cenário atual da ranicultura no estado do Rio de Janeiro, o presente trabalho executou levantamento de dados referentes aos produtores de rã fluminense por meio de formulário online. De uma maneira geral, a ranicultura no Rio de Janeiro não conseguiu apresentar grandes melhorias em termos de estruturação. Sua dinâmica ainda está atrelada a empreendimentos com baixa produção, familiar, pouca inserção no mercado e não formalizados, englobando aspectos relacionados às questões fiscais, ambientais e sanitárias. Assim, o processo de reestruturação da cadeia ranícola no estado depende da superação dos gargalos apontados neste estudo, principalmente referentes à disponibilização de informação acerca dos aspectos de manejo e regularização da produção.(AU)

Gastrointestinal parasites in bullfrogs (Lithobates catesbeianus) in aquaculture production units in the Mexican central highlands / Parasitos gastrointestinais em rãs-touro (Lithobates catesbeianus) em unidades de produção aquícola do planalto central do México

In Mexico, intensive production of bullfrogs is one of the most important aquaculture activities, due to growing demand for their meat. Frogs can be hosts for several parasites that negatively affect their development and health. The objective of this study was to identify the presence of intestinal parasites in bullfrogs in aquaculture production units. Eighteen bullfrogs aquaculture production units were selected, and 20 animals (n=360) from each farm. Fecal samples were obtained by mucosal scraping and processed using the concentration method. The overall prevalence of intestinal parasites was 70.5%, and all farms had frogs infected by some species of parasite. Two species of parasites were identified: Eimeria sp. and Strongyloides sp. Significant differences were found regarding parasite prevalence between males and females (73.8% vs 58.8%) and regarding tibia length (5.5 vs 6.1 cm) and weight (168 vs 187 g) between parasitized and non-parasitized frogs. In conclusion, the present study showed a high prevalence of intestinal parasites, and morphometric alterations (weight, snout-cloaca length, radio-ulna length, tibia length and distance between parotid glands) were identified in the parasitized animals. These results provided useful information that will enable establishment of adequate control measures to help minimize the adverse effects of these parasites.(AU)

No México, a produção intensiva de rãs-touro é uma das atividades mais relevantes da aquicultura devido à sua crescente demanda. As rãs podem ser hospedeiras de vários parasitos que afetam negativamente seu desenvolvimento e sua saúde animal. O objetivo deste trabalho é identificar a presença de parasitas gastrointestinais (IPs) em rãs de boi em unidades de produção aquícola. Foram selecionadas 18 unidades de produção aquícola de rãs-touro, e de cada unidade 20 animais (n=360). Amostras fecais foram obtidas por raspagem de mucosas e processadas pelo método de concentração. A prevalência geral de IPs foi de 70,5%, todas as fazendas foram infectadas com algum parasita. Duas espécies de parasitas Eimeria sp. e Strongyloides sp. foram identificadas; encontrando-se diferenças significativas na prevalência entre machos e fêmeas (73,8% vs 58,8%), comprimento da tíbia (5,5 vs 6,1 cm) e peso (168 vs 187 g) entre rãs parasitadas e não parasitadas. Em conclusão, o presente estudo mostrou uma alta prevalência e alterações morfométricas (peso, comprimento do ronco-cloaca, comprimento do rádio-ulna, comprimento da tíbia e distância entre as glândulas parótidas) todas identificadas nos animais parasitados. Esses resultados mostram informações relevantes que permitirão o estabelecimento de medidas de controle adequadas para ajudar a minimizar os efeitos adversos desses parasitas.(AU)

Condición física e inflamatoria antes de una intervención quirúrgica mayor abdominal / Physical and inflammatory condition before major abdominal quirurgical intervention

Introducción: El desacondicionamiento físico se asocia con disminución en la capacidad cardiorrespiratoria, aumento en el contenido de grasa corporal, e imbalances en respuesta inflamatoria, todos ellos factor de riesgo frente a la agresión de una intervención quirúrgica mayor. El valor de consumo de oxígeno (VO2max), el índice de masa corporal (IMC) y los valores plasmáticos de citoquinas de pacientes programados para una intervención quirúrgica mayor abdominal a menudo no se tienen en cuenta en la valoración prequirúrgica. Objetivo: Determinar la condición física e inflamatoria de pacientes que se trataron con una intervención quirúrgica mayor abdominal. Métodos: Investigación cuantitativa, descriptiva. Muestra por conveniencia de pacientes que se trataron con una intervención quirúrgica mayor abdominal en dos hospitales de Manizales (Colombia). Previo a la intervención, se midió VO2max, el IMC y valores de citoquinas. Resultados: Participaron en el estudio 6 hombres y 48 mujeres. Los valores promedio del VO2max se categorizaron como bajos. Se encontraron valores altos de IMC, del receptor antagonista de IL-1 (IL-1 Ra) y del factor neutrotrófico derivado del cerebro (BDNF). No se hallaron diferencias significativas en los valores promedio de VO2max, de IL-1Ra y de BDNF entre los grupos. Los pacientes programados para intervención quirúrgica ginecológica y gastrointestinal tuvieron sobrepeso y los programados para intervención quirúrgica bariátrica fueron obesos mórbidos. Conclusión: Pacientes programados para una intervención quirúrgica mayor abdominal presentan valores bajos de VO2max para la edad y altos de IMC. Se hallaron valores altos de IL-1Ra y de BDNF asociadas a obesidad y a posible antiinflamación(AU)

Introduction: Physical deconditioning is associated with, a decrease in cardiorespiratory capacity, an increase in body fat content and imbalances in the inflammatory response, all of which are risk factors for the aggression of a major surgical intervention. The oxygen consumption value (VO2max), body mass index (BMI), and plasma cytokine values of patients scheduled for major abdominal surgery are often not taken into account in the presurgical evaluation. Objective: To determine the physical and inflammatory condition of patients who were treated with a major abdominal surgery. Methods: Quantitative, descriptive research. Convenience sample of patients who underwent major abdominal surgery in two hospitals in Manizales (Colombia). Prior to the intervention, VO2max, BMI and cytokine values were measured. Results: 6 men and 48 women participated in the study. Average VO2max values were categorized as low. High values of BMI, IL-1 receptor antagonist (IL-1 Ra) and brain derived neutrotrophic factor (BDNF) were found. No significant differences were found in the mean VO2max, IL-1Ra and BDNF values between the groups. Patients scheduled for gynecological and gastrointestinal surgery were overweight and those scheduled for bariatric surgery were morbidly obese. Conclusion: Patients scheduled for major abdominal surgery have low VO2max values for age and high BMI. High IL-1Ra and BDNF values were found associated with obesity and possible anti-inflammation(AU)

Sinus Node Artery Occlusion During Cardiac Denervation Procedures.

Cardioneural ablation is a novel treatment for functional bradycardia. However, the risk of acute complications is still unknown. The aim of this case report is to describe acute occlusion of the sinus node artery after cardiac denervation procedures in 2 patients and to encourage measures to prevent it, such as evaluating the aortic angulation in older patients before the procedure and by monitoring signs of sinus failure during ablation in patients with electroanatomical maps showing a constricted aspect of the right atrium. (Level of Difficulty: Advanced.).