The impact of integrase inhibitors on the development of hepatic steatosis and fibrosis in HIV-monoinfected patients

Introdução: A Non-alcoholic Fatty Liver Disease (NAFLD) tem uma elevada prevalência nos doentes com infeção pelo VIH. Uma vez que os inibidores da integrase (INSTIs) são usados a nível mundial e têm sido associados a ganho de peso, é importante determinar o seu efeito no desenvolvimento de NAFLD e Non-alcoholic Steatohepatitis (NASH) nestes doentes. O objetivo deste estudo foi determinar o impacto dos INSTIs no risco de desenvolver esteatose e fibrose hepáticas no doente com infeção pelo VIH, através do uso do Hepatic Steatosis Index (HSI), do Fibrosis-4 Index (FIB-4), do BARD score e do NAFLD Fibrosis Score (NFS). Métodos: Foi realizado um estudo observacional de coorte retrospetivo unicêntrico em doentes com infeção pelo VIH que nunca tinham realizado terapêutica antirretroviral (TAR) e que iniciaram INSTIs entre dezembro de 2019 e janeiro de 2022. Os dados foram recolhidos na baseline, aos 6 e aos 12 meses após o início da terapêutica. As características demográficas, clínicas e laboratoriais e os índices de esteatose e fibrose hepáticas foram comparados entre a baseline e a última visita, aos 12 meses. Modelos de regressão linear foram realizados de modo a analisar as associações entre os dados analíticos na baseline e a variação dos índices hepáticos ao longo dos 12 meses de seguimento. Os modelos foram realizados com e sem ajuste para a idade e para o sexo. Resultados: 99 doentes foram incluídos no estudo. Oitenta e dois por cento eram do sexo masculino e a mediana de idades era 36 anos. Foi observado um aumento significativo do índice de massa corporal, do HDL, da contagem de plaquetas, da albumina e da creatinina e uma diminuição significativa dos níveis de AST. O HSI não demonstrou diferenças estatisticamente significativas durante o seguimento (p=0.114). Foi observada uma diminuição significativa do FIB-4 (p=0.007) e do NFS (p=0.002). O BARD score mostrou um aumento significativo (p=0.006). No modelo de regressão linear, foi demonstrada uma associação negativa significativa entre o VIH RNA e a variação do FIB-4 (β= -0.08, 95% CI [-0.16 to -0.00], p=0.045), sugerindo que cargas mais elevadas de VIH RNA na baseline se associam com uma maior diminuição do FIB-4. Conclusão: Os INSTIs parecem não demonstrar impacto na esteatose hepática, embora tenham sido associados a um aumento significativo do índice de massa corporal. Isto pode ser explicado pelo efeito direto do uso de regimes terapêuticos com dolutegravir e/ou pelo "return-to-health effect" observado com o início da TAR. Por fim, os INSTIs foram associados a uma redução do risco de fibrose hepática nos doentes com monoinfeção pelo VIH, possivelmente devido ao seu efeito na supressão vírica.Background: Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among patients with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs in the development of liver steatosis and fibrosis in the patient with HIV infection, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). Methods: We performed a monocentric, retrospective cohort study in HIV-monoinfected cART-naïve patients that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. Results: 99 patients were included in our study. Eighty-two percent were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p=0.114). We observed a significant decrease in FIB-4 (p=0.007) and NFS (p=0.002). BARD score showed a significant increase (p=0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (β= -0.08, 95% CI [-0.16 to -0.00], p=0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. Conclusion: INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the "return-to-health effect" observed with cART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in HIV-monoinfected patients, possibly due to their effect on viral suppression

Food consumption and nutritional knowledge in athletes: a systematic literature review

Sports nutrition involves the application of nutritional principles to improve the performance of individuals who practice some sporting modality. The nutritional knowledge of the athlete is relevant, to acquire competences in the correct choice of food, in order to meet the daily energy needs. METHODS The objective of the systematic review is to evaluate the food consumption of athletes and their nutritional knowledge. The bibliographic research was carried out in the databases PubMed And Science Direct, According to the guidelines PRISMA and Collaboration Cochrane (Galvão, Pansani, & Harrad, 2015) for the period between 2008-2018. After applying the inclusion and exclusion criteria, 12 articles were selected from a total of 1130 articles. RESULTS The inadequacy of energy (Praz, Granges, Burtin, & Kayser, 2015) consumption and the carbohydrate (Coutinho, Porto, & Pierucci, 2016) intake deficit was 50% (n = 6) of the articles analyzed. Regarding protein (M. Sousa et al., 2016) and total saturated fat consumption, 25% (n = 3), showed excessive consumption according to recommendations. In the micronutrient intake there was a deficit of vitamins and minerals in 42% (n = 5) of the articles. In the water intake, the prevalence of inadequacy was 33% (n = 4). Regarding food frequency, there was a low intake of fruits and vegetables, at least 42% (n = 5) of the articles and cereals in 33% (n = 4). About nutritional knowledge, the articles that evaluate it (n = 3): 67% (n = 2) have investigated that the Average nutritional knowledge index was higher than 50% (Alaunyte, Perry, & Aubrey, 2015), verifying a statistically significant association between food consumption and nutritional knowledge (p < 0.05). CONCLUSIONS The obtained results allowed the observation that most of the athletes do not have an adequate diet for their respective sport practice. It is imperative to reinforce research on the nutritional knowledge of athletes.The authors thank to FCT-Portugal and the ERDF through the program PT2020, the funding granted to CIMO (UID /AGR/00690/2013).info:eu-repo/semantics/publishedVersio

Combining exercise with education based on transformative learning principles in fibromyalgia patients: a case series

Proceeding de trabalho apresentado no 7th World, 7 a 10 de maio, Congress of the World Institute of Pain, Maastricht, Holand

Negative modulation of human osteoclastogenesis by antiepileptic drugs

Bone is constantly being molded and shaped by the action of osteoclasts and osteoblasts. A proper equilibrium between both cell types metabolic activities is required to ensure an adequate skeletal tissue structure, and it involves resorption of old bone and formation of new bone tissue. It is reported that treatment with antiepileptic drugs (AEDs) can elicit alterations in skeletal structure, in particular in bone mineral density. Nevertheless, the knowledge regarding the effects of AEDs on bone cells are still scarce, particularly on osteoclastic behaviour. In this context, the aim of this study was to investigate the effects of five different AEDs on human osteoclastic cells. Osteoclastic cell cultures were established from precursor cells isolated from human peripheral blood, and were maintained in the absence (control) or in the presence of 10-8-10-4 M of different AEDs (valproate, carbamazepine, gabapentin, lamotrigine and topiramate). Cell cultures were characterized throughout a 21-day period for tartrate-resistant acid phosphatase (TRAP) activity, number of TRAP+ multinucleated cells, presence of cells with actin rings and expressing vitronectin and calcitonin receptors, and apoptosis rate. Also, the involvement of several signaling pathways on the cellular response was addressed. All the tested drugs were able to affect osteoclastic cell development, although with different profiles on their osteoclastogenic modulation properties. Globally, the tendency was to inhibit the process. Furthermore, the signaling pathways involved in the process also seemed to be differentially affected by the AEDs, suggesting that the different drugs may affect osteoclastogenesis through different mechanisms. In conclusion, the present study showed that the different AEDs had the ability to negatively modulate the osteoclastogenesis process, shedding new light towards a better understanding of how these drugs can affect bone tissue

ADENOPATIA CERVICAL COMO MANIFESTAÇÃO DE CANCRO DO CÓLON

Introduction: Colorectal cancer is one of the most frequent cancers worldwide, being the third most common cancer diagnosed and corresponding to the second cause of death by cancer. Approximately 25% of patients have already disseminated disease at the time of diagnosis. Case Report: We present the case of a 68-year-old female patient presented with complaints of cervical mass. She was then submitted to a biopsy of the cervical adenopathy that revealed metastatic adenocarcinoma tissue with probable gastrointestinal origin. A work-up was performed and revealed a sigmoid colon adenocarcinoma. Due to associated morbidities she was submitted to supportive treatment. Discussion: This case demonstrates the singularity of metastatic pattern in colon carcinoma. The mechanism of distant lymph node metastases in colorectal cancer still remains uncertain, nevertheless this represents an advanced stage of the disease that bears a poor prognosis. Conclusion: Few reports in the literature showed a good outcome with primary tumor excision and adjuvant chemotherapy but this decision should be discussed in a multidisciplinary team in order to decide the best treatment option for each patient.Introdução: O cancro colorectal é um dos cancros mais frequentes a nível mundial, sendo o terceiro cancro mais frequentemente diagnosticado e corresponde à segunda causa de morte por cancro. Cerca de 25% dos doentes apresentam doença disseminada à data de diagnóstico. Caso Clínico: Os autores apresentam o caso de uma doente de 68 anos, do sexo feminino, que se apresentou com queixas de uma tumefacção cervical. Foi posteriormente submetida a biópsia excisional que revelou a presença de metástase de adenocarcinoma provavelmente intestinal. Foi realizado o estudo complementar com identificação de um adenocarcinoma do cólon sigmoide. Devido às morbilidades associadas foi oferecido tratamento de suporte. Discussão: Este caso representa a singularidade do padrão de metastização do cancro do cólon. O mecanismo de metastização ganglionar à distância não se encontra totalmente esclarecido, no entanto, representa um estadio de doença avançado com um mau prognóstico associado. Conclusão: Alguns casos na literatura demonstraram bons resultados com a excisão do tumor primário seguida de quimioterapia adjuvante, esta decisão deve ser realizada por uma equipa multidisciplinar de forma a avaliar a melhor opção terapêutica para cada doente

Differential effects of antiepileptic drugs on human bone cells

Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.info:eu-repo/semantics/publishedVersio

Staphylococcus aureus inactivation in a non-ready-to-eat sausage during maturation: a dynamic model

The aim of this study was to model the effect of annatto (Bixa orellana) extract against S. aureus (SA) in a Portuguese non-ready-to-eat meat product (alheira sausage) during maturation. Alheira batter was prepared with 0.0%, 0.5%, 1.0%, or 1.5% of lyophilised annatto extract and stuffed in pre-washed natural casings following inoculation with SA, then hung in a climatic-controlled chamber at 10 °C for 13 days. For every treatment, a dynamic model was adjusted and adequately fitted to all survival curves with residuals and root mean square errors between 0.0008–0.0016 and 0.029–0.040, respectively, producing significant parameter estimates. Therefore, the addition of annatto extracts significantly shortened the shoulder phase and decreased the time to achieve one log reduction, which, in practical terms, corresponded to up to 1.35 [SE = 0.08] log CFU/g reduction by the end of the 13-day maturation.U. Gonzales-Barron would like to thank the national funding by FCT, through the institutional scientific employment program-contract.info:eu-repo/semantics/publishedVersio

Microbial deterioration of lamb meat of portuguese origin as affected by its intrinsic properties

In Portugal, sheep and goat meat production constitutes 2.8% of the total meat production, with a self-sufficiency of ~82%. The main autochthonous sheep breeds exploited for meat production are Churra-Galega-Bragançana (CGB) and Bordaleira-de-Entre-Douro-e-Minho (BEDM), whose quality must be optimised in order to ensure adequate income levels for sheep producers. The study aimed to characterise the evolution of spoilage microorganisms in refrigerated vacuum-packed (VP) lamb meat from BEDM and CGB breeds; and elucidate how intrinsic properties of meat can affect its microbial spoilage. Meat from BEDM breed presented higher (p<.0001) populations of mesophiles, lactic acid bacteria, Pseudomonas spp. and psychrotrophic bacteria, since its higher ultimate pH (means: 5.77 for BEDM vs. 5.58 for CGB) accelerated spoilage rate (p<.0001). While water activity and protein content were not found to modulate microbial deterioration (p>0.05), the growth of spoilage bacteria was found to be exacerbated by higher moisture (p<.0001) and higher ash content (p<0.001). By contrast, a higher fat content retarded (p<.0001) the growth of spoilage bacteria in VP lamb meat. In order to extend the shelf-life of Portuguese-origin lamb meat, animal handling must be enhanced to minimise pre-slaughter stress, and a carcass classification system should be adopted towards the selection of fatter animals and chilled carcasses of optimal ultimate pH.info:eu-repo/semantics/publishedVersio

Atmospheric plasma and UV polymerisation for developing sustainable anti-adhesive polyethylene terephthalate (PET) surfaces

Enhancing the hydrophilicity of polymeric materials is an important step for achieving anti-adhesiveness. Thus, in this study, atmospheric plasma as a pre-treatment was combined with a UV grafting process to obtain a durable surface modification on polyethylene terephthalate (PET). The most promising conditions for the atmospheric plasma process were found to be 15 kW power and 4 m/min speed, leading to a contact angle reduction from 70 ± 6° to approximately 30°. However, it was observed that these values increased over time due to the ageing and washing of the PET surface, ultimately causing it to recover its initial contact angle. Therefore, the plasma-pre-treated PET samples were further modified through a UV grafting process using sodium acrylate (NaAc) and 3-sulfopropyl acrylate potassium salts (KAc). The grafted acrylate PET samples exhibited contact angles of 8 ± 3° and 28 ± 13° for NaAc and KAc, respectively, while showing durability in ageing and washing tests. The dry film thicknesses for both samples were found to be 28 ± 2 μm. Finally, the anti-adhesive properties of the NaAc- and KAc-treated surfaces were evaluated using an Escherichia coli expressing YadA, an adhesive protein from Yersinia. The modified PET surfaces were highly effective in reducing bacterial adhesion by more than 90%.This work was supported by the ViBrANT project, which received funding from the EU Horizon 2020 Research and Innovation Programme under Marie Sklowdowska-Curie (grant agreement no. 765042), and the Portuguese Foundation for Science and Technology (FCT) (grant number UIDB/04469/2020).info:eu-repo/semantics/publishedVersio