Early morphological and neurochemical changes of the bed nucleus of stria terminalis (BNST) in gestational protein-restricted male offspring.

BACKGROUND: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear. AIM: The present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring. METHODS: Dams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography. RESULTS: Serum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blot analysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes.

Molecular sensitization profile to grass and olive pollens in Portugal.

Summary: Background. Grass and olive pollens have overlapping pollination periods and are common allergens in the Iberian Peninsula. The objective is to determine the sensitization pattern to major Phleum pratense and Olea europaea pollens in the Portuguese population with pollen allergic rhinitis (AR) using molecular allergen diagnosis (MAD). Methods. Seasonal AR patients (≥ 12 years), with positive skin prick tests (SPT) to Phleum and Olea were recruited from 16 centers. Using ALEX2, specific IgE to Phl p1, Phl p2, Phl p5, Phl p6, Phl p7, Phl p 12, Ole e1, Ole e7 and Ole e9 were determined. Immunoblotting of Olea allergic patients was performed. Results. Included 175 patients (55.4% female; mean age 31.6 ± 13.3 years; 85.7% adults; 40% asthmatic, Coast 28%/Inland 72% and North 29.1%/Centre 20.6%/South 50.3%). Considering Phleum MAD, 85.7% were sensitized to Phl p1, 45.7% to Phl p2, 50.3% to Phl p5, 45.7%, to Phl p6, 10.9% to Phl p7 and 22.9% to Phl p12. Sensitization to Ole e1 was found in 56.6%, to Ole e7 in 1.7% and Ole e9 in 3.4% patients. Sensitization to Phl p7 was more frequent in asthmatics (17.4% vs 6.6%; p = 0.044). Sensitization to Phl p5, Phl p6, Phl p12 and Ole e1 was more frequent in inland. Regarding sensitization patterns: 53.1% patients were sensitized to both species genuine´ sIgE, 38.3% to Phleum and 3.4% only to Olea species' sIgE. Immunoblotting of Olea allergic patients showed a high intensity band that may correspond to Ole e12. Conclusions. MAD showed "genuine" Grass and Olea sensitization in approximately 50% of our patients.

Dupilumab in patients with atopic dermatitis: assessing treatment response, clinical features and potential biomarkers in real-life.

Summary: Background. The clinical and pathophysiological heterogeneity of atopic dermatitis (AD) endophenotypes is associated with wide diversity in response to therapy. The aim of this study was to evaluate the response to dupilumab in a group of AD patients and identify clinical/immunological features associated with different patterns of response. Methods. A retrospective observational study was performed, including 30 adults with AD who completed 12 months treatment with dupilumab, in a Portuguese Immunoallergology Department. Demographic, clinical, and immunological data were analyzed, including total serum IgE, sensitization to aeroallergens, peripheral eosinophilia and inflammatory biomarkers (sedimentation rate, C-reactive protein and lactate dehydrogenase-LDH). Patients who achieved EASI-75/EASI ≤ 7, SCORAD-75/SCORAD ≤ 24, NRS-pruritus ≤ 4 or DLQI≤5 at 6 months of treatment were considered responders and those that achieved all these goals at 16 weeks were considered super-responders. Results. Clinical evaluation revealed a significant reduction in median SCORAD, EASI, DLQI, NRS-pruritus and NRS-sleep over 12 months on dupilumab (p less than 0.01), in parallel with decrease in serum Th2 pathway biomarkers and LDH. All patients responded to dupilumab, and 26.7% were super-responders, supporting that dupilumab is highly effective in moderate to severe Th2-high AD. Conclusions. In this cohort, none of the evaluated biomarkers at baseline were associated with a better/earlier clinical response to dupilumab. Dupilumab treatment for 52 weeks resulted in a significant and sustained reduction in blood levels of total IgE and allergen-specific IgE to aeroallergens. The potential long-term clinical benefit of these effects, even after discontinuing dupilumab therapy in patients with AD, should be explored to a greater extent.

World trends in publication for maxillofacial and dental trauma in the elderly.

Aging may increase the risk of maxillofacial and dentoalveolar trauma (MDT). This review assessed global trends in scientific publications on MDT in the elderly. Six databases were searched. Studies about MDT in the elderly (≥60 years old) were included in two text mining stages (S1 and S2). In S1, all studies with elderly subjects were included, while in S2 only studies in which the elderly were assessed in a separate set of data or in a subanalysis by age groups were included. In S1, relevant data were mined using VantagePoint™ software. In S2, data were descriptively analyzed. There were 2265 studies at S1 and 110 at S2. The publication dates spanned from 1963 to 2023. In S1, the most cited keywords and terms were aged (n = 1872), male (n = 1839), female (n = 1777), "mandible fracture" (n = 460), "orbit fracture" (n = 362), and "maxilla fracture" (n = 118). Thirty authors published 10 or more articles with visible collaboration networks. There was a progressive increase in publications, especially in Europe (n = 150). In S2, most studies were case reports/case series (n = 62). The primary etiology was accidental falls (n = 84), the most affected region was the middle third of the face (n = 65), and dental trauma was rarely reported (n = 15). Cone Beam computed tomography was the most used diagnostic tool (n = 67). Of the 81 articles that addressed therapy, 52 opted for surgical treatment. Although there has been an increase in the number of articles on MDT over the years, studies with the elderly population as a specific study group are still needed. Accidental falls were the most reported etiology, while the middle third of the face and the mandible were the anatomic region and bone most affected, respectively. The high number of case reports indicates the need for improvement in the available scientific evidence about MDT in the elderly.

Delayed postoperative reactions to metamizole: a diagnostic challenge.

Summary: Background. Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed drug hypersensitivity reactions. Due to its favorable pharmacokinetic characteristics, metamizole is widely used in the postoperative period for pain control. Methods. Retrospective study of patients referred for allergological study between January 2012 and June2022 for postoperative hypersensitivity reactions. Clinical and diagnostic data were collected through review of patients' medical records. Twenty patients with postoperative hypersensitivity reactions were referred, of which 10 presented delayed reactions. We analyzed the results of skin prick, intradermal and patch tests performed with an intravenous metamizole solution as well as provocation tests performed with metamizole and acetylsalicylic acid. Cross-reactivity to non-steroidal anti-inflammatory drugs was excluded by confirmation of clinical tolerance to non-steroidal anti-inflammatory drugs or by acetylsalicylic acid provocation test. Results. In 7 of the 10 patients a delayed reaction to metamizole was diagnosed. These reactions were characterized as maculopapular exanthema, occurring in multiple postoperative settings. Skin tests were negative, except in one patient with late mild erythema in the ipsilateral upper limb and no reaction at the site of intradermal injection. Delayed hypersensitivity was demonstrated by late positive metamizole provocation tests. Conclusions. This study demonstrated that for a correct diagnosis a high degree of suspicion about possible delayed hypersensitivity drug reactions to metamizole in the postoperative setting is needed. In the investigation, provocation test with metamizole was decisive for diagnostic confirmation.

Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs on a pediatric Portuguese cohort.

Summary: Background. Non-steroidal anti-inflammatory drugs (NSAID)/analgesics (paracetamol) are among the most common causes of drug hypersensitivity reactions in children, with a reported prevalence of around 0.3% in the pediatric population. Paracetamol and ibuprofen are the most commonly reported culprits in the pediatric population. Our objective was to describe the allergy workup to NSAID/paracetamol of a pediatric population monitored in an allergy outpatient clinic. Methods. Retrospective observational study by consulting the medical records of patients evaluated in a pediatric outpatient clinic with history of NSAID/paracetamol, between January 2016 to August 2022. Results. A total of 43 patients have been evaluated for NSAID/paracetamol suspected allergy: 53.5% females, mean age of 9.8 ± 5.1 years, 47.7% atopic. The drugs reported as culprits were: ibuprofen (75.6%), paracetamol (17.8%), metamizole (4.4%) and naproxen (2.2%) and clinical manifestations were mainly urticaria/angioedema and maculopapular exanthema. Skin tests were performed in 7 patients: paracetamol (n = 5) and metamizole (n = 2), which were all negative. Fourty-six drug provocation tests were performed: 28 with the culprit drug and 18 with an alternative one; only 2 were positive (ibuprofen - culprit NSAID group): one immediate periorbital angioedema and one delayed lip edema with oropharyngeal tightness. Conclusions. The investigation of allergy to NSAID/paracetamol in children remains a challenge. In our population, ibuprofen was the most common NSAID reported. There were only 2 (4.3%) mild reactions on DPT. We could allow the use of the culprit NSAID/analgesic in 11 patients and an alternative one in 9 patients. This study highlights the importance of DPT in children for a correct diagnosis of NSAID hypersensitivity and selection of an alternative drug.

Suppressing star formation in quiescent galaxies with supermassive black hole winds.

Quiescent galaxies with little or no ongoing star formation dominate the population of galaxies with masses above 2 × 10(10) times that of the Sun; the number of quiescent galaxies has increased by a factor of about 25 over the past ten billion years (refs 1-4). Once star formation has been shut down, perhaps during the quasar phase of rapid accretion onto a supermassive black hole, an unknown mechanism must remove or heat the gas that is subsequently accreted from either stellar mass loss or mergers and that would otherwise cool to form stars. Energy output from a black hole accreting at a low rate has been proposed, but observational evidence for this in the form of expanding hot gas shells is indirect and limited to radio galaxies at the centres of clusters, which are too rare to explain the vast majority of the quiescent population. Here we report bisymmetric emission features co-aligned with strong ionized-gas velocity gradients from which we infer the presence of centrally driven winds in typical quiescent galaxies that host low-luminosity active nuclei. These galaxies are surprisingly common, accounting for as much as ten per cent of the quiescent population with masses around 2 × 10(10) times that of the Sun. In a prototypical example, we calculate that the energy input from the galaxy's low-level active supermassive black hole is capable of driving the observed wind, which contains sufficient mechanical energy to heat ambient, cooler gas (also detected) and thereby suppress star formation.

Treatment of fruit processing wastewater by electrochemical and activated persulfate processes: Toxicological and energetic evaluation.

A fruit processing wastewater was submitted to different advanced oxidation processes, namely, electro-Fenton (EF), electrochemical oxidation (EO), activated persulfate (PS), and combined EF/PS. The performance of the treatment processes, at different experimental conditions, regarding organic load removal, biodegradability increment, toxicity reduction, and specific energy consumption (Esp), was evaluated. At the experimental conditions studied, EO led to the treated solutions with the highest biodegradability increment, from 0.24 to 0.48, and toxicity reduction towards Daphnia magna, from 5.8 to 1.5 toxic units, without requiring the addition of chemicals. Nevertheless, the highest chemical oxygen demand (COD) removals were obtained for EF and combined EF/PS treatments. For the electrochemical processes, an increase in COD removal rate with applied current density (j) was observed. However, the increase in j substantially raised the Esp. In PS treatment, COD removals above 80% were only achieved for high amounts of added persulfate and iron, which led to less biodegradable and more toxic solutions. Combined EF/PS attained the lowest Esp values, mainly due to the conductivity increase originated by the persulfate and iron salts addition. Besides the disadvantage of the chemicals added, this combined treatment led to treated solutions with very acidic pH and significant iron content.

Subcutaneous immunotherapy with aeroallergens: safety profile assessment.

SUMMARY: Introduction. Severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT) are rare but local reactions (LR) are common. We aimed to characterize the type of reactions and safety profile. Methods. Retrospective analysis of medical record from patients under SCIT between 2013-2016. Results. Total of 7372 SCIT injections in 323 patients: 52% female; mean age 30 years (SD 13); mean treatment time 19 months (SD 13). There were 57 patients (17.6% of population, 70% female) with at least one adverse reaction, for 93 reactions described (1.3% injections). There were 79 LR (1.1% injections) in 46(14.2%) patients: 36 in build-up, 43 in maintenance. There were 14 SR (0.19% injections) in 12(3.7%) patients: 12 in build-up, 2 in maintenance. All SR were grade 1. The majority of reactions were caused by mite SCIT (69.9%). Conclusions. SCIT is safe and well tolerated, with no report of SR grade > 1.

Hereditary angioedema: 24 years of experience in a Portuguese Reference Center.

Summary: Hereditary angioedema (HAE) poses a high burden of disease, being its epidemiological and clinical data heterogeneous among countries, with no recent published studies concerning Portuguese patients. Therefore, we aimed to raise awareness of HAE and to contribute to clinical knowledge. An observational, descriptive, retrospective, and cross-sectional study was performed, that included a cohort of 126 patients followed in a single Portuguese Center. We observed a high prevalence of HAE-C1-INH type II (45.2% of patients). Most HAE patients (67.4%) presented the initial manifestations of the disease before adulthood, at a mean age of 12.6 ± 8.4 years. However, we found a long delay in HAE diagnosis, especially in those without family history (mean 20.7 ± 17.3 years). Stress was the most common trigger, followed by trauma and infection. Symptoms involving different systems were increasingly reported with increased disease duration. Cutaneous symptoms (95.0%) were more frequent, followed by gastrointestinal (80.7%), and respiratory symptoms (50.4%). HAE symptoms led to abdominal surgery in 22 (17.5%) patients and induced laryngeal edema requiring intubation/tracheostomy in 8 (6.3%) patients. Most patients were under long-term prophylaxis, mainly with attenuated androgens (62.7% of patients).The correct distinction between HAE and other common causes of angioedema is critical, allowing reduction of diagnostic delay, improvement of adequate management, and ultimately improving outcomes and quality of life of HAE patients.

Abuse among Portuguese older people at a time of economic crisis recovery: findings from the Harmed study.

This study aimed to assess the prevalence of abuse against Portuguese older people after an economic crisis and to assess how it has influenced health. A cross-sectional study was carried out including 677 older adults (≥60 years) during 2017. Results show that overall, 23.9% of older people reported being a victim of abuse in the last 12 months. The prevalence of psychological abuse was 19.9%, financial abuse 5.8%, physical abuse 2.5% and sexual abuse 1.9%. Older people who report abuse were more likely to have perceived insufficient income and low social support. The abuse was also significantly associated with poor health status and depressive symptoms. Even in an auspicious period, more than a fifth of older people experiences abuse which is associated with social and health vulnerabilities. These results support that an investment should be made in terms of policies toward an age-friendly environment.

North African dust intrusions and increased risk of respiratory diseases in Southern Portugal.

The study of dust intrusions in Portugal is still a subject on which little investigation has been made, especially in terms of their effects. Thus, this work aims to achieve two goals: firstly, to characterize the dust intrusions in the study area; and secondly, to evaluate the possible statistical association between the dust intrusion days and hospital admissions due to respiratory diseases. Dust intrusions in Portugal are prevalent during the summer season. During this season, the dust plumes tend to cover broader areas than in the other seasons and they have origin in the North African countries. In the study area for the period between 2005 and 2015, the relative risk of urgent hospitalizations due to respiratory diseases was 12.6% higher during dust intrusion days. In order to obtain this statistical association, a Distributed Lag Nonlinear Model was developed. With this work, we expect to help the development of further studies regarding North African dust intrusions in Portugal, more precisely their effects on human health.

Feasibility of using magnetic nanoparticles in water disinfection.

Disinfection is a crucial step during the water treatment process due to the significant risks of water contamination with human and animal excreta. The development of innovative disinfection technologies that can be applied at water point of use, avoiding contamination problems in water distribution systems and reservoirs, are needed. Thus, the present work aimed at assessing the disinfection efficiency of iron oxide magnetic nanoparticles (MNPs) modified with different compounds, such as carbon nanotubes, copper and silver, in water solutions contaminated with bacteria. Kinetic and influence of nanoparticles concentration experiments, performed with Escherichia coli, allowed to define the optimal reaction conditions to apply in batch experiments (1 min of contact time and 50 mg/mL of MNPs). During these experiments, CuFeO/CNT, C-FeO@CVD750 and 5% Ag/FeO were selected as the most efficient presenting log reduction values of 2.99, 1.50 and 2.11, respectively; however, experiments performed with Staphylococcus aureus suspension and a mixed bacterial suspension (E. coli + S. aureus) allowed to observe a slight decrease in nanomaterials efficiency, which was more evident for C-FeO@CVD750 and 5% Ag/FeO materials achieving efficiencies of 94 and 83% (corresponding log reductions of 1.26 and 0.77, respectively). CuFeO/CNT nanoparticles proved to be the most efficient material for both bacteria removal presenting an efficiency of 99% (corresponding log reduction of 1.99) for the mixed bacterial suspension. These nanoparticles proved to have great stability over successive experiments, and the low leaching values of the metals present in their composition after reaction proved the resistance and efficiency of these magnetic nanoparticles.

Impact of compliance to chemoradiation on long-term outcomes in squamous cell carcinoma of the anus: results of a post hoc analysis from the randomised phase III ACT II trial.

BACKGROUND: Concurrent chemoradiation is standard-of-care for patients with squamous cell carcinoma of the anus. Poor compliance to chemotherapy, radiotherapy treatment interruptions and unplanned breaks may impact adversely on long-term outcomes. METHODS: The ACT II trial recruited 940 patients with localised squamous cell carcinoma of the anus, and assigned patients to mitomycin (week 1) or cisplatin (weeks 1 and 5), with fluorouracil (weeks 1 and 5) and radiotherapy (50.4 Gy in 28 fractions over 38 days). This post hoc analysis examined the association between baseline factors (age, gender, site, T stage and N stage), and compliance to treatment (radiotherapy and chemotherapy), and their effects on locoregional failure-free survival, progression-free survival (PFS) and overall survival (OS). Compliance was categorised into groups. Radiotherapy: six groups according to total dose and overall treatment time (OTT). Chemotherapy: three groups (A = per-protocol; B = dose reduction or delay; C = omitted). RESULTS: A total of 931/940 patients were assessable for radiotherapy and 936 for chemotherapy compliance. Baseline glomerular filtration rate <60 ml/min and cisplatin were significantly associated with poor week 5 compliance to chemotherapy (P = 0.003 and 0.02, respectively). Omission of week 5 chemotherapy was associated with significantly worse locoregional failure-free survival [hazard ratio (HR) 2.53 (1.33-4.82) P = 0.005]. Dose reductions/delays or omission of week 5 chemotherapy were associated with significantly worse PFS {HR: 1.56 [95% confidence interval (CI): 1.18-2.06], P = 0.002 and HR: 2.39 (95% CI: 1.44-3.98), P = 0.001, respectively} and OS [HR: 1.92 (95% CI: 1.41-2.63), P < 0.001 and HR: 2.88 (95% CI: 1.63-5.08), P < 0.001, respectively]. Receiving the target radiotherapy dose in >42 days is associated with worse PFS and OS [HR: 1.72 (95% CI: 1.17-2.54), P =0.006]. CONCLUSION: Poor compliance to chemotherapy and radiotherapy were associated with worse locoregional failure-free survival, PFS and OS. Treatment interruptions should be minimised, and OTT and total dose maintained. CLINICAL TRIAL NUMBER: ISRCTN 26715889.

Atopic Dermatitis Host and Environment Model: Revisiting Therapeutic Options.

Summary: Atopic Dermatitis affects both children and adults and is a serious health concern in many countries. AD is a complex disease with host and environmental factors underlying its pathology. Its treatment is multidimensional reflecting the diverse nature of its triggers and includes emollients, topical steroids and calcineurin inhibitors among others. Immunological dysfunction can be addressed broadly with systemic immunosupressors and specifically with monoclonal antibodies. Dupilumab, which targets IL-4 and IL-13 was granted approval for treatment of moderate-to-severe AD. Biologics targeting IgE/Th2 pathways may have its role in patients with overlapping AD and asthma. Psychological distress can exacerbate symptoms and is associated with increased severity of AD. Environmental triggers, such as, allergens can be addressed in selected cases with allergic immunotherapy. In this paper, we discuss AD treatment and propose a new step-by-step approach aiming at maintaining disease control and improving quality of life.

Subcutaneous immunotherapy with aeroallergens Evaluation of adherence in real life.

Summary: Introduction. Adherence in allergen immunotherapy is crucial for its efficacy. At least 3 years of treatment are recommended for achieving a long-term modifying effect. Objectives. To assess patient's adherence and to identify determinant factors for allergen subcutaneous immunotherapy (SCIT) suspension in patients with respiratory allergy. Methods. Retrospective analysis of the medical record of patients submitted to SCIT between January 2013 and December 2016 in our Department. Results. 323 patients were included: 52% female; mean age 30±13 years; average treatment time 19±13 months. 52 patients (16%) stopped SCIT: 54% female; mean age 30±9 years; average treatment time 12±6 months; 67% dropped the treatment during the 1st year, 27% in the 2nd and 6% during the 3rd year of treatment. Adherence rate determined was 77%. The most frequent reasons for withdrawal were due to economic reasons (47.9%), followed by patients' perception of no clinical improvement (23%) and change to sublingual immunotherapy (11.6%). Conclusion. Adherence rate in our study was 77%. Economic reasons were the main cause of abandonment in the first year, while the perception of non improvement was the main reason for abandonment in subsequent years. Adequate information on SCIT prescribing and rigorous monitoring of patients during the treatment can improve adherence.

IL4-10 fusion protein: a novel immunoregulatory drug combining activities of interleukin 4 and interleukin 10.

The objective of this study was to test the capacity of a newly developed fusion protein of interleukin 4 (IL-4) and IL-10 [IL4-10 fusion protein (FP)] to shift multiple pro-inflammatory pathways towards immune regulation, and to inhibit pro-inflammatory activity in arthritis models. The effects of IL4-10 FP in comparison with IL-4, IL-10 and IL-4 plus IL-10 on pro- and anti-inflammatory mediators, T cells and immunoglobulin (Ig) receptors in favour of immunoregulatory activity were studied. In addition, the capacity of IL4-10 FP to inhibit pro-inflammatory activity in ex-vivo and in-vivo arthritis models was investigated. IL4-10 FP robustly inhibited pro-inflammatory cytokine [IL-1ß, tumour necrosis factor (TNF)-α, IL-6 and IL-8] production in whole blood cultures, mediated by both the IL-10 and the IL-4 moiety. IL4-10 fusion protein induced IL-1 receptor antagonist (IL-1RA) production and preserved soluble TNF receptor (sTNFR) levels, strongly increasing IL-1RA/IL-1ß and sTNFR/TNF-α ratios. In addition, IL4-10 FP strongly inhibited T helper (Th) type 1 and 17 cytokine secretion, while maintaining FoxP3 expression and up-regulating Th2 activity. In addition, while largely leaving expression of activating Fc gamma receptor (FcγR)I, III and Fc epsilon receptor (FcεR) unaffected, it significantly shifted the FcγRIIa/FcγRIIb ratio in favour of the inhibitory FcγRIIb. Moreover, IL4-10 FP robustly inhibited secretion of pro-inflammatory cytokines by rheumatoid arthritis synovial tissue and suppressed experimental arthritis in mice, without inducing B cell hyperactivity. IL4-10 fusion protein is a novel drug, signalling cells to induce immunoregulatory activity that overcomes limitations of IL-4 and IL-10 stand-alone therapy, and therefore has therapeutic potential for inflammatory diseases such as rheumatoid arthritis.

Modulation of reactive oxygen levels and gene expression in sensitive and resistant tumoral cells by C-phyocyanin.

In this work we investigated the possible cellular changes induced by C-phycocyanin (C-PC) in erythroleukemic cells with (K562-Lucena and FEPS) and without (K562) the multidrug resistance (MDR) phenotype. The reactive oxygen levels (ROS) (evaluated by fluorimetry) were increased relative to the control in K562 and K562-Lucena cells treated with 100 µg/mL and were not increased in FEPS cells. The expression of the following genes related to resistance was evaluated by real-time PCR: COX2, ALOX5, ABCB1 and ABCC1. Treatment with 100 µg/mL of C-PC increased COX2 and ABCB1 expression in K562-Lucena cells and reduced expression of ALOX5 in K562-Lucena and FEPS cells. ROS levels appear to be involved in biological responses to C-PC in K562 and K562-Lucena cells, although expression of the genes studied here was only modified by C-PC in the K562-Lucena cell line. Thus, it is possible to suggest that C-PC modulates the expression of COX2 and ABCB1 for the K562-Lucena in a ROS-dependent manner and the expression of ALOX5 for the FEPS in a ROS-independent manner; however, more studies are needed to elucidate these mechanisms.

Total polyphenol intake, polyphenol subtypes and incidence of cardiovascular disease: The SUN cohort study.

BACKGROUND AND AIMS: Polyphenol-rich diets have been associated with reduced risk of cardiovascular disease (CVD). However, few prospective epidemiological studies have examined the relationship between classes of ingested polyphenols and risk of CVD. Our aim was to evaluate the association between polyphenol intake and risk of major cardiovascular events in a prospective Spanish cohort. METHODS AND RESULTS: We included 17,065 university graduates (60.7% women, mean age: 37.2 years, age range: 20-89) followed-up for a mean of 10.1 years. Polyphenol intake was assessed at baseline using a validated semi-quantitative 136-item food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for incident cardiovascular events (myocardial infarction, stroke or cardiovascular death). Cherries, chocolate, coffee, apples, and olives were the major sources of variability in polyphenol intake. Participants with higher flavonoids intake (fifth quintile) had a 47% lower incidence of cardiovascular events compared to those in the lowest quintile (HR: 0.53, 95% CI: 0.29-0.98; P for trend = 0.09) after adjusting for potential confounders. The results were non-significant for other polyphenol types. CONCLUSION: The intake of flavonoids showed an inverse association with risk of cardiovascular events in a prospective cohort of Spanish middle-aged adult university graduates. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT02669602 in Clinical Trials.

Does access to healthy food vary according to socioeconomic status and to food store type? an ecologic study.

BACKGROUND: The food environment can influence opportunities and barriers to food access. This study aimed to investigate whether access to healthy foods varies according to store types and the socioeconomic status of the users of the public health promotion program in Brazil, known as the Health Academy Program. METHODS: A total of 18 Health Academy Program centers were selected via simple conglomerate sampling. Health Academy Program users living up to 1 km from the food stores were evaluated (n = 2831). Their socioeconomic status was investigated via face-to-face interviews. The food stores were audited through direct observation. Variables included the community nutrition environment (type and location) and consumer nutrition environment (healthy food store index, involving variables such as availability, variety, and advertising of healthy and unhealthy products). Multiple linear regression analysis was performed to examine the association between access to healthy foods, socioeconomic status, and food store type. RESULTS: A total of 336 stores were investigated. The majority were specialty fruit and vegetable markets/stores or open-air food markets. Access to healthy food was only associated with the food store type. An increase of 1% in the availability of specialized fruits and vegetable markets or open-air food markets and supermarket raised healthy food store index values by 0.12 and 0.07, respectively. CONCLUSIONS: Public food supply policies aimed at improving the diet quality of the population and reducing inequality in access should prioritize the implementation of stores of better quality, such as specialty fruit and vegetable markets and open-air food markets.