A study protocol for a randomized controlled trial of an anti-inflammatory nutritional intervention in patients with fibromyalgia

BackgroundThis study aims to analyze the effects of a potentially anti-inflammatory nutritional intervention in disease assessment parameters, inflammatory markers, and quality of life of fibromyalgia (FM) patients.MethodsA sample of 100 female patients diagnosed with FM, followed up at Portuguese Institute of Rheumatology (IPR) in Lisbon, is being randomly allocated in two groups. Patients in the intervention group are adopting an anti-inflammatory diet, characterized by the exemption of the intake of foods containing gluten, dairy, sugar, and ultra-processed foods, during 3months. During the first month, a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) diet is implemented, along with the anti-inflammatory diet, followed by the reintroduction of all fruits and vegetables over a consecutive period of 2months. Patients in the control group are adopting a diet based on general recommendations for healthy eating. The outcomes are pain, fatigue, quality of sleep, quality of life, gastrointestinal symptoms, and inflammation. Before and after the 3months intervention, and also 1month after beginning the intervention, the following questionnaires are applied: Revised Fibromyalgia Impact Questionnaire, visual analog pain scale, Brief Pain Inventory,visual analog scale from a list of common gastrointestinal and extraintestinal symptoms in FM, Short Form 36, Fatigue Severity Survey, and Pittsburg Sleep Quality Index. Ultra-sensitive serum C-reactive protein, eritrocyte sedimentation rate, and interleukin-8 are determined. Age, physical activity, anthropometric parameters, and body composition are being collected. Student's t test will assess the association between the disease evaluation parameters, the inflammatory markers, and the dietary interventions.DiscussionThe results of this study are expected to determine whether a change in patient nutrition helps to alleviate symptoms, which would optimize medical intervention.Trial registrationwww.ClinicalTrials.gov NCT04007705. Registered on July 5, 2019

An anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols diet improved patient reported outcomes in fibromyalgia: A randomized controlled trial

Background: Fibromyalgia (FM) has been associated with dysbiosis and low-grade inflammation. Studies have reported that diet influences clinical features in FM. Objective: To evaluate the effect of an anti-inflammatory and low fermentable oligo, di, and monosaccharides and polyols (FODMAP) diet on clinical outcomes of patients with FM. Methods: This two arms Randomized Controlled Trial (NCT04007705) included 46 female patients with FM. The intervention group (n = 22) adopted an anti-inflammatory diet for 3 months, excluding gluten, dairy, added sugar, and ultra-processed foods, along with a low FODMAPs diet in the first month. The control group (n = 24) followed general healthy eating recommendations. Both diets were applied by a certified dietitian. Before and after the intervention, participants were assessed regarding pain, fatigue, gastrointestinal symptoms, quality of sleep, and quality of life, through the Revised Fibromyalgia Impact Questionnaire (FIQR), Visual Analogue Pain Scale (VAS), Visual Analog Scale from gastrointestinal symptoms (VAS GI), Brief Pain Inventory (BPI), Pittsburg Sleep Quality Index (PSQI), Fatigue Severity Survey (FSS), and The Short Form Health Survey (SF-36). A blood sample was collected and high-sensitive C-Reactive Protein and Erythrocyte Sedimentation Rate were quantified. Paired Samples t-test/Wilcoxon and independent samples t-test/Mann-Whitney were used to compare variables between groups. Results: After intervention, there was an improvement in intervention group scores of FIQR (p = 0.001), VAS (p = 0.002), BPI (p = 0.011), FSS (p = 0.042), VAS_GI (p = 0.002), PSQI (p = 0.048), and SF36 (p = 0.045) compared to control group. Inflammatory biomarkers (hs-CRP, ESR) did not change in both groups. The intervention was beneficial in the intervention group, regardless of age, disease duration, body mass index variation, and body fat change between baseline and post-intervention. Conclusion: An anti-inflammatory and low-FODMAP diet improved clinical features in patients with FM and may be useful as a complement to pharmacological therapy

A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status

Background: Comorbidity and socioeconomic status (SES) may be related among cancer patients. Method : Population-based cancer registry study among 72 153 patients diagnosed during 1997-2006. Results : Low SES patients had 50% higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity. Conclusion : This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions

Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis

Background: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. Methods: Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. Results: All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. Conclusion: These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) grant ref. PTDC/SAU-FCF/104347/2008, under the scope of ‘Programa Operacional Temático Factores de Competitividade’ (COMPETE) of ‘Quadro Comunitário de Apoio III’ and co-financed by the Fundo Europeu De Desenvolvimento Regional (FEDER). Ricardo Amorim was recipient of the fellowship SFRH/BD/98002/2013, from Fundação para a Ciência e a Tecnologia (FCT Portugal).info:eu-repo/semantics/publishedVersio

Synthesis and anti-HSV-1 evaluation of new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines

Background: Herpes simplex virus type-1 (HSV-1) is the primary cause of facial lesions (mouth, lips, and eyes) in humans. The widespread use of acyclovir and nucleoside analogues has led to emergence of HSV strains that are resistant to these drugs. Recently, non-nucleoside anti-HSV compounds have received considerable attention. 1,6-Naphthyridines are a class of heterocyclic compounds that exhibit a broad spectrum of biological activities such as inhibitor of HIV-1 integrase, HCMV, FGF receptor-1 tyrosine kinase, and the enzyme acetylcholinesterase. We previously reported the synthesis, SAR studies, and evaluation anti-HSV-1 activity of 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines. In the course of our search for new 1,6-naphthyridines derivatives with potential activity against HSV-1, we have synthesized and evaluated new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines (1a-k) and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines (2a-c). Results: A known synthetic approach was used for preparing new 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines (1a-k) and 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines (2a-c), starting from ethyl 4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (7). All compounds were identified by FTIR, 1H NMR, and mass spectrometry. The antiviral effect on HSV-1 virus replication was determined. Conclusions: The compounds 1d, 1f, 1g, and 1h exhibited the highest anti-HSV-1 activity. In general, 3H-benzo[b]pyrazolo[3,4-h]-1,6-naphthyridines were more effective inhibitors than their corresponding 3H-pyrido[2,3-b]pyrazolo[3,4-h]-1,6-naphthyridines. The compound 1h reduced the virus yield in 91% at 50 μM and exhibited a low cytotoxicity (CC50 600 μM)

Antenatal glucocorticoid treatment induces adaptations in adult midbrain dopamine neurons, which underpin sexually dimorphic behavioral resilience

We demonstrated previously that antenatal glucocorticoid treatment (AGT, gestational days 16-19) altered the size and organization of the adult rat midbrain dopaminergic (DA) populations. Here we investigated the consequences of these AGT-induced cytoarchitectural disturbances on indices of DA function in adult rats. We show that in adulthood, enrichment of striatal DA fiber density paralleled AGT-induced increases in the numbers of midbrain DA neurons, which retained normal basal electrophysiological properties. This was co-incident with changes in (i) striatal D2-type receptor levels (increased, both sexes); (ii) D1-type receptor levels (males decreased; females increased); (iii) DA transporter levels (males increased; females decreased) in striatal regions; and (iv) amphetamine-induced mesolimbic DA release (males increased; females decreased). However, despite these profound, sexually dimorphic changes in markers of DA neurotransmission, in-utero glucocorticoid overexposure had a modest or no effect on a range of conditioned and unconditioned appetitive behaviors known to depend on mesolimbic DA activity. These findings provide empirical evidence for enduring AGT-induced adaptive mechanisms within the midbrain DA circuitry, which preserve some, but not all, functions, thereby casting further light on the vulnerability of these systems to environmental perturbations. Furthermore, they demonstrate these effects are achieved by different, often opponent, adaptive mechanisms in males and females, with translational implications for sex biases commonly found in midbrain DA-associated disorders

Monitoring biological wastewater treatment processes: Recent advances in spectroscopy applications

Biological processes based on aerobic and anaerobic technologies have been continuously developed to wastewater treatment and are currently routinely employed to reduce the contaminants discharge levels in the environment. However, most methodologies commonly applied for monitoring key parameters are labor intensive, time-consuming and just provide a snapshot of the process. Thus, spectroscopy applications in biological processes are, nowadays, considered a rapid and effective alternative technology for real-time monitoring though still lacking implementation in full-scale plants. In this review, the application of spectroscopic techniques to aerobic and anaerobic systems is addressed focusing on UV--Vis, infrared, and fluorescence spectroscopy. Furthermore, chemometric techniques, valuable tools to extract the relevant data, are also referred. To that effect, a detailed analysis is performed for aerobic and anaerobic systems to summarize the findings that have been obtained since 2000. Future prospects for the application of spectroscopic techniques in biological wastewater treatment processes are further discussed.The authors thank the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge the financial support to Daniela P. Mesquita and Cristina Quintelas through the postdoctoral Grants (SFRH/BPD/82558/2011 and SFRH/BPD/101338/2014) provided by FCT - Portugal.info:eu-repo/semantics/publishedVersio