IL-1 Receptor Contributes to the Maintenance of the Intestinal Barrier via IL-22 during Obesity and Metabolic Syndrome in Experimental Model.

Intestinal permeability and bacterial translocation are increased in obesity and metabolic syndrome (MS). ILC3 cells contribute to the integrity of intestinal epithelium by producing IL-22 via IL-1ß and IL-23. This study investigates the role of IL-1R1 in inducing ILC3 cells and conferring protection during obesity and MS. For this purpose, C57BL/6 wild-type (WT) and IL-1R1-deficient mice were fed a standard diet (SD) or high-fat diet (HFD) for 16 weeks. Weight and blood glucose levels were monitored, and adipose tissue and blood samples were collected to evaluate obesity and metabolic parameters. The small intestine was collected to assess immunological and junction protein parameters through flow cytometry and RT-PCR, respectively. The intestinal permeability was analyzed using the FITC-dextran assay. The composition of the gut microbiota was also analyzed by qPCR. We found that IL-1R1 deficiency exacerbates MS in HFD-fed mice, increasing body fat and promoting glucose intolerance. A worsening of MS in IL-1R1-deficient mice was associated with a reduction in the ILC3 population in the small intestine. In addition, we found decreased IL-22 expression, increased intestinal permeability and bacterial translocation to the visceral adipose tissue of these mice compared to WT mice. Thus, the IL-1R1 receptor plays a critical role in controlling intestinal homeostasis and obesity-induced MS, possibly through the differentiation or activation of IL-22-secreting ILC3s.

RELATIONSHIP BETWEEN RESIDUAL DIURESIS AND SARCOPENIA IN PATIENTS ON HEMODIALYSIS.

OBJECTIVE: To assess the association of residual diuresis with sarcopenia in patients with Chronic Kidney Disease (CKD) on hemodialysis. METHODS: Through a cross-sectional study, patients on hemodialysis were subjected to a Dual Energy Radiologic Absorption (DEXA) exam to record muscle mass. Based on the volume of urine collected in 24 hours, patients were classified as anuric (diuresis ≤ 100 mL/day) or non-anuric (diuresis > 100 mL/day). Functional performance was evaluated by Short Physical Performance Battery (SPPB) and muscle strength by handgrip strength and 5-repetition sit-to-stand test. The association between the absence of residual urine and the presence of sarcopenia, low SPPB, and low muscle strength was analyzed using a binary logistic regression model. RESULTS: Ninety-two patients, with a mean age of 54.4 years (95% CI 51.3 - 57.4) and with a mean diuresis volume of 476.3 mL/day (95% CI 320.4 - 632.2) were evaluated (48 anuric and 44 non-anuric). Anuric patients had a 2.77 (95% CI 1.14 - 6.73) times greater probability of sarcopenia and had a 3.55 (1.14 - 11.0) times greater probability of low SPPB, regardless of gender, age, and time on dialysis. Gender was the other associated variable for the presence of sarcopenia, with males having a 3.30 (95% CI 1.34 - 8.13) times higher risk. There were no associations with muscle strength. CONCLUSION: The absence of residual diuresis in patients on hemodialysis is associated with a higher risk of sarcopenia and low functional performance.

Market-driven fortification of vitamins and minerals in packaged foods targeted at children in Brazil.

This study aimed to characterise the market-driven fortification of vitamins and minerals in packaged foods targeted at children in Brazil. We analysed 535 food labels using data collected in a census-type method (n = 5620) of food labels in a Brazilian supermarket in 2013. Micronutrients declared in nutrition claims and the ingredients list (synthetic compounds) were considered to be added for commercial purposes. Analysis of the ingredients list and nutrition claims showed that market-driven fortification of vitamins and minerals was present in 27.1% of foods. The main vitamins and minerals were vitamins A, B complex, C, D, calcium, iron and zinc. The food groups 'Milk and dairy products' and 'Sugars, sugary foods and snacks' had the highest frequencies of micronutrients declared in the ingredients list. Calcium, iron, phosphorus, zinc and all vitamins, except B7, were found to be added for commercial purposes. Micronutrients were found to be commonly added to packaged foods as a marketing strategy directed at parents and their children. Future studies should assess the amount of vitamins and minerals added to packaged foods targeted at children and whether intakes of vitamins and minerals in children are potentially excessive.

A real-world cross-sectional study evaluating the role of an oral amino acid-based supplement in nutrient intake by preschoolers on a cow's milk elimination diet.

INTRODUCTION AND OBJECTIVES: Food allergy has several negative nutritional consequences and may persist beyond the first year of lives. This study aimed to assess the role of a complete oral amino acid-based supplement in the diet of children on cow's milk protein elimination diet because of food allergy. MATERIALS AND METHODS: This study included two groups of children aged 1-5 years paired by age and socioeconomic status: (1) study group, on cow's milk protein elimination diet plus an oral amino acid-based supplement, and (2) control group, on cow's milk protein elimination diet. Sociodemographic, clinical, anthropometric, and dietary data were obtained through online interviews. Two 24-h dietary recalls were collected on nonconsecutive days. Both groups comprised mostly boys. RESULTS: The study group presented lower values of body mass index. The frequency of feeding difficulties was similar between groups. The study group had a higher intake of energy, protein, carbohydrates, calcium, iron, zinc, phosphorus, magnesium, copper, selenium, vitamins D, E, B1, B2, B6, and B12, niacin, and folic acid compared to the control group. A higher proportion of children in the study group had adequate intake according to the recommendations made for energy, carbohydrates, iron, phosphorus, selenium, vitamins A, D, E, B1, B2, and B6, and folic acid. CONCLUSIONS: The use of a complete oral amino acid-based supplement has a positive effect on the diet quality of preschoolers on cow's milk elimination diet because of food allergy, promoting higher intake of energy, calcium, vitamin D, and other essential nutrients.

Modifications to the parasitological technique of Rugai increase the diagnostic sensitivity for strongyloidiasis.

Strongyloidiasis is a neglected tropical disease caused mainly by Strongyloides stercoralis, a nematode that can persist for decades in the human host with a very low parasitic burden and without specific symptoms. Hence, it is difficult to diagnose and control. Larval concentration and culture methods with fecal samples show higher sensitivity for the diagnosis of Strongyloides-infected individuals; however, these techniques are not routinely used, primarily due to the challenges associated with processing a substantial volume of fecal samples. In the current study, we comparatively evaluated the sensitivity and applicability of modifications made to the Rugai parasitological method for the diagnosis of strongyloidiasis in fecal samples of experimentally infected rats and in 68 individuals from an urban community close to Maceió, Brazil. The presence and quantity of parasite larvae in the feces were comparatively evaluated using different parasitological techniques. In the experimental model, we demonstrated that the modified Rugai technique (RMOD) allowed for significantly higher recovery of larvae than the original Rugai technique (RO). Moreover, the sediment was cleaner and easier to evaluate using optical microscopy. Compared to other parasitological techniques, such as agar-plate culture (A-PC) and spontaneous sedimentation (SS), the RMOD technique showed higher sensitivity in the detection of larvae in all infected groups and presented comparatively better performance, especially in rats with a low parasite burden. In the human population, among the 68 stool samples evaluated, Strongyloides larvae were detected in the feces of six individuals with an estimated prevalence of 8.82%. However, the performance of each parasitological method was remarkably different. SS identified Strongyloides larvae in only two individuals and A-PC in three, whereas RMOD was able to identify six infected individuals, resulting in sensitivities of 33.3%, 50%, and 100%, respectively. In conclusion, the modifications introduced to the Rugai technique resulted in improved sensitivity for the detection of Strongyloides spp. infections, especially in stool samples with a low parasite burden, in comparison with other routinely used parasitological techniques.

Reliability and validity of the Patient Generated Index (PGI) in patients with chronic kidney disease (CKD) on dialysis, a new approach to quality of life.

PURPOSE: To evaluate the test-retest reliability and validity of the Patient Generated Index (PGI) in individuals with Chronic Kidney Disease (CDK) undergoing hemodialysis. METHODS: Through a non-experimental study with repeated measures, PGI was applied twice to assess internal consistency and test-retest reliability. Correlations with the Kidney Disease Quality of Life Short Form (KDQOL-SF), the Human Activity Profile (HAP) questionnaire, the Social Participation Scale, and the Glittre ADL Test were used. RESULTS: 91 individuals with CKD were evaluated. There was high reliability for the PGI (ICC= 0.97) PGI correlated with KQDOL - SF in Functional Capacity r = 0.38 (p < 0.001), Emotional Well-Being r = 0.31 (p = 0.003), Social Aspect r = 0.22 (p = 0.036), Emotional Function r = 0.22 (p = 0.038) and Effect of Kidney Disease r = 0.21 (p = 0.042), and Physical scores r = 0.24 (p = 0.021)), Mental r = 0.21 (p = 0.05) and General r = 0.22 (p = 0.037) summarized. There was a significant correlation between PGI and HAP r = 0.40 (p < 0.001) and the Social Participation Scale r = -0.36 (p < 0.001). There was no correlation between the PGI and Glittre ADL scores r = 0.12 (p = 0.247). CONCLUSION: In adults receiving hemodialysis, the PGI proved to be an accurate and reliable instrument for the assessment of the quality of life from the perspective of the patient.IMPLICATIONS FOR REHABILITATIONAlthough hemodialysis treatment is associated with increased survival and symptom control, there is a significant change in the patient's lifestyle.In order to provide a more focused view of the individual, the Patient Generated Index (PGI) was created to evaluate the quality of life.PGI is reliable and correlates with KQDOL - SF and the Social Participation Scale in this population.

Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model.

Gut dysbiosis is linked to type 1 diabetes mellitus (T1D). Inulin (INU), a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how INU affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied INU's protective effects. Remarkably, STZ + INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared with STZ + SD mice. STZ + INU mice also had enhanced mucus production, abundant Bifidobacterium, Clostridium cluster IV, Akkermansia muciniphila, and increased fecal butyrate. In cecal lymph nodes, we observed fewer CD4+Foxp3+ regulatory T cells expressing CCR4 and more Foxp3+CCR4+ cells in pancreatic islets, with higher CCL17 expression. This phenotype was absent in CCR4-deficient mice on INU. INU supplementation effectively protects against experimental T1D by recruiting CCR4+ regulatory T cells via CCL17 into the pancreas and altering the butyrate-producing microbiota.

Optimization of the Erythrosine-mediated photodynamic therapy against Escherichia coli using response surface methodology.

BACKGROUND: The efficacy of photodynamic therapy (PDT) depends on the combination of light and a photosensitizer for inactivation of microorganisms. However, finding the ideal conditions for the factors involved in this technique is time and cost-consuming. The rotational composite central design (RCCD) is a tool that can be allied with PDT to achieve precise results within a shorter working time. METHODS: This study used the response surface methodology to optimize the parameters of PDT mediated by Erythrosine (ERY) and green light-emitting diodes (LED) in different Escherichia coli strains by applying RCCD. RESULTS: The RCCD predicted optimum values of ERY and light exposure on PDT. According to the experimental results, the light exposure time showed the most significant influence on the inactivation of the evaluated bacteria. The optimized operating conditions were validated in laboratory tests, and no viable cells were recovered with ERY at 116 µmol L-1 and 30 min of light (33.34 J cm2) for E. coli ATCC 25922, 108 µmol L-1 and 40 min (44.38 J cm2) for E. coli ATCC 35218, and 108 µmol L-1 and 29.3 min (32.5 J cm2) for E. coli O157:H7 EDL 933. CONCLUSION: The adjusted polynomial models provided accurate information on the combined effects of ERY and lighting time with green LED on PDT. The application of the RCCD, in addition to reducing the number of experiments, also allows for increased quantity and quality of the results. Therefore, surface response methodology combined with PDT is a promising approach to inactivate E. coli.

AT1 receptors modulate ethanol-induced loss of anticontractile effect of perivascular adipose tissue.

Ethanol consumption activates renin-angiotensin-aldosterone system (RAAS), which plays a major role in the pro-contractile and hypertensive effects linked to ethanol. We hypothesized that ethanol consumption induces loss of the anticontractile effect of perivascular adipose tissue (PVAT)through RAAS-mediated mechanisms. We examined the contribution of angiotensin II type 1 receptors (AT1R) to ethanol-induced PVAT dysfunction. With this purpose, male Wistar Hannover rats were treated with ethanol 20 % (in volume ratio) and/or losartan (antagonist of AT1R; 10 mg/kg/day, gavage) for 9 weeks. Losartan prevented the increase in blood pressure and the loss of the anticontractile effect of PVAT induced by ethanol consumption. PVAT dysfunction occurred after 3 and 9 weeks of treatment with ethanol in an endothelium-dependent manner. Blockade of AT1R prevented ethanol-induced reduction of adiponectin levels in PVAT from ethanol-treated rats. Functional assays revealed that ethanol impaired the anticontractile effect of PVAT-derived angiotensin (1-7) and endothelial nitric oxide (NO). In conclusion, AT1R are implicated in ethanol-induced loss of the anticontractile effect of PVAT. In PVAT, AT1R activation decreases the production of adiponectin, a PVAT-derived factor that promotes vasorelaxation in an endothelium-dependent manner. In the endothelium, AT1R favors the production of superoxide (O2•-) leading to a reduction in NO bioavailability. These responses impair the vasodilator action induced by PVAT-derived angiotensin (1-7), which occurs via Mas receptors located in endothelial cells. Ethanol-induced PVAT dysfunction favors vascular hypercontractility, a response that could contribute to the hypertensive state associated with ethanol consumption.

The Th2 Response and Alternative Activation of Macrophages Triggered by Strongyloides venezuelensis Is Linked to Increased Morbidity and Mortality Due to Cryptococcosis in Mice.

Cryptococcosis is a systemic mycosis that causes pneumonia and meningoencephalitis. Strongyloidiasis is a chronic gastrointestinal infection caused by parasites of the genus Strongyloides. Cryptococcosis and strongyloidiasis affect the lungs and are more prevalent in the same world regions, i.e., Africa and tropical countries such as Brazil. It is undeniable that those coincidences may lead to the occurrence of coinfections. However, there are no studies focused on the interaction between Cryptococcus spp. and Strongyloides spp. In this work, we aimed to investigate the interaction between Strongyloides venezuelensis (Sv) and Cryptococcus gattii (Cg) in a murine coinfection model. Murine macrophage exposure to Sv antigens reduced their ability to engulf Cg and produce reactive oxygen species, increasing the ability of fungal growth intracellularly. We then infected mice with both pathogens. Sv infection skewed the host's response to fungal infection, increasing lethality in a murine coinfection model. In addition to increased NO levels and arginase activity, coinfected mice presented a classic Th2 anti-Sv response: eosinophilia, higher levels of alternate activated macrophages (M2), increased concentrations of CCL24 and IL-4, and lower levels of IL-1ß. This milieu favored fungal growth in the lungs with prominent translocation to the brain, increasing the host's tissue damage. In conclusion, our data shows that primary Sv infection promotes Th2 bias of the pulmonary response to Cg-infection and worsens its pathological outcomes.

Prostatic Artery Embolization Using Polyethylene Glycol Microspheres: A 1-Year Follow-up Prospective Study Including 30 Patients.

PURPOSE: To evaluate safety and effectiveness of prostatic artery embolization (PAE) using polyethylene glycol (PEG) microspheres in patients with moderate-to-severe benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A single-center, prospective study of 30 patients who underwent PAE from August 2020 to December 2021 using PEG 400-µm microspheres was conducted. Patient evaluation data using International Prostate Symptom Score (IPSS), quality of life (QoL) score, prostate-specific antigen (PSA), peak urinary flow rate (Qmax), postvoid residual volume (PVR), and prostate volume (PV) at baseline and 3 and 12 months after PAE were obtained. RESULTS: Bilateral PAE was performed in all patients. One patient had early clinical failure (3.3%) and another presented with lower urinary tract symptoms (LUTSs) recurrence (3.3%) at the 12-month follow-up. Twenty-eight patients (93.3%) experienced significant and durable LUTS improvement. Mean absolute (and relative) improvement at 3 and 12 months were: IPSS, 14.6 points (-69%) for both; QoL, 3.3 points (-70%) and 3.5 points (-74%); Qmax, 6.3 mL/s (+78%) and 8.6 mL/s (+100%); PSA reduction, 1.2 ng/mL (-22%) and 1.0 ng/mL (-15%); PVR reduction, 48 mL (-56%) and 58.2 mL (-49%); PV reduction, 23.4 cm3 (-29%) and 19.6cm3 (-25%); (P < .05 for all). No major adverse events were observed. Minor adverse events included urinary tract infection (4/30, 13.3%), prostatic tissue elimination (3/30, 10%), penile punctiform ulcer (1/30, 3.3%), and urinary retention (1/30, 3.3%). CONCLUSIONS: PAE using PEG microspheres was observed to be effective with sustained LUTS improvement at the 12-month follow-up. The incidence of urinary infection and prostatic tissue elimination was higher than previously reported for other embolics.

AraC interacts with p75NTR transmembrane domain to induce cell death of mature neurons.

Cytosine arabinoside (AraC) is one of the main therapeutic treatments for several types of cancer, including acute myeloid leukaemia. However, after a high-dose AraC chemotherapy regime, patients develop severe neurotoxicity and cell death in the central nervous system leading to cerebellar ataxia, dysarthria, nystagmus, somnolence and drowsiness. AraC induces apoptosis in dividing cells. However, the mechanism by which it leads to neurite degeneration and cell death in mature neurons remains unclear. We hypothesise that the upregulation of the death receptor p75NTR is responsible for AraC-mediated neurodegeneration and cell death in leukaemia patients undergoing AraC treatment. To determine the role of AraC-p75NTR signalling in the cell death of mature neurons, we used mature cerebellar granule neurons' primary cultures from p75NTR knockout and p75NTRCys259 mice. Evaluation of neurite degeneration, cell death and p75NTR signalling was done by immunohistochemistry and immunoblotting. To assess the interaction between AraC and p75NTR, we performed cellular thermal shift and AraTM assays as well as Homo-FRET anisotropy imaging. We show that AraC induces neurite degeneration and programmed cell death of mature cerebellar granule neurons in a p75NTR-dependent manner. Mechanistically, Proline 252 and Cysteine 256 residues facilitate AraC interaction with the transmembrane domain of p75NTR resulting in uncoupling of p75NTR from the NFκB survival pathway. This, in turn, exacerbates the activation of the cell death/JNK pathway by recruitment of TRAF6 to p75NTR. Our findings identify p75NTR as a novel molecular target to develop treatments for counteract AraC-mediated cell death of mature neurons.

Qualitative menu labelling in university restaurants and its influence on food choices: A systematic review and synthesis without meta-analysis.

Qualitative menu labelling can be defined as descriptive or non-numerical interpretive labels (e.g. traffic light labelling, healthy food symbols, messages or ingredient lists). Qualitative information seems to have a positive influence on consumers' food choices, particularly in institutional food service establishments, such as in universities. The aim of this systematic review was to assess the influence of different formats of qualitative menu labelling on food choices in university restaurants. This systematic review was guided by the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) and Synthesis Without Meta-Analysis (SWiM) and conducted vote counting of studies based on the direction of effect. Studies were retrieved from Cochrane Library, Scopus, MEDLINE, LILACS, SciELO and Web of Science databases and reference lists of selected articles. Experimental and quasi-experimental studies were included. Two independent researchers searched and extracted the data and assessed the methodological quality using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. From the initial search (460 records), four papers were selected, plus one paper identified in a previous study and a further six from an update search, totalling 11 included studies, reporting 14 different interventions (n = 499 174). Types of interventions included the use of symbols and the inclusion of traffic light labelling. Outcomes of interest were food choice, expressed as mean, median or percent healthy food choices or purchases. Qualitative menu labels increased healthy food choices and/or purchase behaviour, with 10 of 12 interventions favouring the intervention (83%; 95%CI 55-95%; p = 0.0386). Most of the studies favouring the intervention used healthy food symbols for healthier foods or food components, alone or in association with another intervention and were of moderate and weak quality. These findings may serve as a basis for the implementation of nutrition information policies in university restaurants.

Nicotine exposure during breastfeeding alters the expression of endocannabinoid system biomarkers in female but not in male offspring at adulthood.

Early nicotine exposure compromises offspring's phenotype at long-term in both sexes. We hypothesize that offspring exposed to nicotine during breastfeeding show deregulated central and peripheral endocannabinoid system (ECS), compromising several aspects of their metabolism. Lactating rats received nicotine (NIC, 6 mg/Kg/day) or saline from postnatal day (PND) 2 to 16 through implanted osmotic minipumps. Offspring were analyzed at PND180. We evaluated protein expression of N-acylphosphatidylethanolamide-phospholipase D (NAPE-PLD), fatty acid amide hydrolase (FAAH), diacylglycerol lipase (DAGL), monoacylglycerol lipase (MAGL) and cannabinoid receptors (CB1 and/or CB2) in lateral hypothalamus, paraventricular nucleus of the hypothalamus, liver, visceral adipose tissue (VAT), adrenal and thyroid. NIC offspring from both sexes did not show differences in hypothalamic ECS markers. Peripheral ECS markers showed no alterations in NIC males. In contrast, NIC females had lower liver DAGL and CB1, higher VAT DAGL, higher adrenal NAPE-PLD and higher thyroid FAAH. Endocannabinoids biosynthesis was affected by nicotine exposure during breastfeeding only in females; alterations in peripheral tissues suggest lower action in liver and higher action in VAT, adrenal and thyroid. Effects of nicotine exposure during lactation on ECS markers are sex- and tissue-dependent. This characterization helps understanding the phenotype of the adult offspring in this model and may contribute to the development of new pharmacological targets for the treatment of several metabolic diseases that originate during development.

Xenogeneic mesenchymal stem cell biocurative improves skin wounds healing in diabetic mice by increasing mast cells and the regenerative profile.

Introduction: Diabetes mellitus (DM) is a chronic disease and a major cause of mortality and morbidity worldwide. The hyperglycemia caused by DM induces micro and macrovascular complications that lead, among other consequences, to chronic wounds and amputations. Cell therapy and tissue engineering constitute recent therapeutic alternatives to improve wound healing in diabetic patients. The current study aimed to analyze the effectiveness of biocuratives containing human mesenchymal stem cells (MSCs) associated with a hydrogel matrix in the wound healing process and related inflammatory cell profile in diabetic mice. Methods: Biocuratives containing MSCs were constructed by 3D bioprinting, and applied to skin wounds on the back of streptozotocin (STZ)-induced type 1 diabetic (T1D) mice. The healing process, after the application of biocuratives with or without MSCs was histologically analyzed. In parallel, genes related to growth factors, mast cells (MC), M1 and M2 macrophage profiles were evaluated by RT-PCR. Macrophages were characterized by flow cytometry, and MC by toluidine blue staining and flow cytometry. Results: Mice with T1D exhibited fewer skin MC and delayed wound healing when compared to the non-diabetic group. Treatment with the biocuratives containing MSCs accelerated wound healing and improved skin collagen deposition in diabetic mice. Increased TGF-ß gene expression and M2 macrophage-related markers were also detected in skin of diabetic mice that received MSCs-containing biocuratives. Finally, MSCs upregulated IL-33 gene expression and augmented the number of MC in the skin of diabetic mice. Conclusion: These results reveal the therapeutic potential of biocuratives containing MSCs in the healing of skin wounds in diabetic mice, providing a scientific base for future treatments in diabetic patients.

Establishing and characterizing a novel doxorubicin-resistant acute myeloid leukaemia cell line.

Drug resistance is a major setback in cancer treatment, thus models to study its mechanisms are needed. Our work aimed to establish and characterize a resistant cell line from a sensitive acute myeloid leukaemia (AML) cell line - HL60 - by treating the sensitive cells with increasing concentrations of doxorubicin. We confirmed (cell viability assays) that the established subline, HL60-CDR, was resistant to doxorubicin for at least 30 days without drug treatment. The HL60-CDR cells were also resistant to three other drugs (cisplatin, etoposide and daunorubicin), exhibiting a multidrug resistant (MDR) profile. We verified (Western Blotting) that the MDR cells do not express drug efflux pumps, nor present altered expression of apoptotic proteins, when compared with the parental cell line. HL60-CDR cells presented alterations in the cell cycle profile, and in the expression levels of proteins involved in DNA repair mechanisms and drug metabolism, when compared with their drug sensitive counterpart. Proteomic analysis revealed that HL60-CDR cells presented an upregulation of proteins involved in oncogenic pathways, such as TSC2, PDPK1, Annexin A2, among others. Overall, we established an AML MDR subline - HL60-CDR - which presents several resistance mechanisms, providing an in vitro model to test new compounds to circumvent MDR in AML.

Levels of adherence to contemporary antiretroviral regimens and the likelihood of viral suppression: a cohort study in a Brazilian metropolis.

Levels of adherence to antiretroviral therapy (ART) can affect the likelihood of viral suppression differentially among ART regimens. In this prospective cohort conducted in Belo Horizonte, Brazil, we included 354 individuals who initiated ART containing tenofovir disoproxil fumarate/lamivudine/efavirenz in fixed-dose combination (TDF/3TC/EFV) or tenofovir disoproxil fumarate/lamivudine associated with dolutegravir (TDF/3TC + DTG). Viral suppression (viral load <50 copies/mL) was evaluated within six months of follow-up at different adherence levels and by therapeutic regimen. Adherence was measured by the Proportion of Days Covered (PDC) and classified into low (≤84%), intermediate (85-89%) or high (≥90%). The association between viral suppression, adherence levels, and other explanatory variables was analyzed using chi-square and multivariable logistic regression. Viral suppression was achieved by 76.0% of individuals and was more frequent among those who achieved higher levels of adherence (high adherence: 79.3%, intermediate: 71.4% and low: 45.2%), those on TDF/3TC + DTG, and those who had viral load ≤100,000 copies/mL at the onset of treatment (p < 0.05). Moreover, individuals on TDF/3TC + DTG had an approximately 90% probability of achieving viral suppression at intermediate adherence levels. These results add new insights on the possibility of lower adherence levels for contemporary antiretroviral regimens currently used as first-line therapy worldwide.

Adaptação de receitas culinárias de um programa de intervenção em habilidades culinárias para indivíduos com diabetes tipo 2: um estudo de viabilidade / Culinary recipes adaptation to a cooking skills intervention program for individuals with type 2 diabetes: a feasibility study

Introdução: Hábitos alimentares saudáveis e habilidades culinárias podem contribuir no tratamento de diabetes mellitus tipo 2. Objetivo: Este estudo visou adaptar nutricionalmente, testar e avaliar qualitativamente as características sensoriais de receitas culinárias para sua aplicação em um programa de intervenção culinária para indivíduos com diabetes tipo 2, denominado Nutrição e Culinária na Cozinha. Método: O programa Nutrição e Culinária na Cozinha é uma intervenção com oficinas culinárias práticas focadas na promoção das habilidades culinárias. As modificações das receitas foram baseadas no índice glicêmico dos ingredientes, depois testadas e discutidas por especialistas em nutrição por meio de oficinas de consenso. Realizaram-se grupos focais com indivíduos com diabetes tipo 2 para avaliar e discutir as características sensoriais das receitas culinárias. Resultados: As adaptações das receitas para atender à população com diabetes tipo 2 incluíram a substituição de arroz por couve-flor e macarrão por abobrinha, além do uso de frutas e especiarias em receitas doces em substituição a ingredientes com açúcares de adição e/ou edulcorantes Essas mudanças foram aprovadas pelos indivíduos com diabetes tipo 2. Conclusão: As receitas culinárias adaptadas poderão ser utilizadas em orientações dietéticas e em intervenções culinárias para promover hábitos alimentares que contribuam para o controle glicêmico.

Introduction: Healthy eating habits and cooking skills can contribute to the treatment of type 2 diabetes mellitus (T2DM). Objective: This study aimed to adapt, test, and qualitatively evaluate the sensory characteristics of food recipes for their application in a culinary intervention program for individuals with type 2 diabetes, called Nutrition and Culinary in the Kitchen. Methods: Nutrition and Culinary in the Kitchen is an intervention program with hands-on cooking classes focused on promoting cooking skills. Recipes' modifications were based on the glycemic index of ingredients, then tested and discussed by nutrition experts in consensus workshops. Individuals with type 2 diabetes assessed and discussed the sensory characteristics of recipes in focus groups. Results: Recipes adaptations to suit type 2 diabetes population included replacement of rice by cauliflower and pasta by zucchini, and the use of fruits and spices in sweet recipes instead of using added sugar ingredients and/or non-caloric sweeteners. Those changes were positively accepted by the individuals with type 2 diabetes. Conclusion: The adapted culinary recipes can be used in dietary guidelines and in cooking interventions to promote eating habits that contribute to glycemic control.

CD18 controls the development and activation of monocyte-to-macrophage axis during chronic schistosomiasis.

Schistosomiasis is a neglected tropical disease caused by worms of the genus Schistosoma spp. The progression of disease results in intense tissue fibrosis and high mortality rate. After egg deposition by adult worms, the inflammatory response is characterized by the robust activation of type 2 immunity. Monocytes and macrophages play critical roles during schistosomiasis. Inflammatory Ly6Chigh monocytes are recruited from the blood to the inflammatory foci and differentiate into alternatively activated macrophages (AAMs), which promote tissue repair. The common chain of ß2-integrins (CD18) regulates monocytopoiesis and mediates resistance to experimental schistosomiasis. There is still limited knowledge about mechanisms controlled by CD18 that impact monocyte development and effector cells such as macrophages during schistosomiasis. Here, we show that CD18low mice chronically infected with S. mansoni display monocyte progenitors with reduced proliferative capacity, resulting in the accumulation of the progenitor cell denominated proliferating-monocyte (pMo). Consequently, inflammatory Ly6Chigh and patrolling Ly6Clow monocytes are reduced in the bone marrow and blood. Mechanistically, low CD18 expression decreases Irf8 gene expression in pMo progenitor cells, whose encoded transcription factor regulates CSFR1 (CD115) expression on the cell surface. Furthermore, low CD18 expression affects the accumulation of inflammatory Ly6Chigh CD11b+ monocytes in the liver while the adoptive transference of these cells to infected-CD18low mice reduced the inflammatory infiltrate and fibrosis in the liver. Importantly, expression of Il4, Chil3l3 and Arg1 was downregulated, CD206+PD-L2+ AAMs were reduced and there were lower levels of IL-10 in the liver of CD18low mice chronically infected with S. mansoni. Overall, these findings suggest that CD18 controls the IRF8-CD115 axis on pMo progenitor cells, affecting their proliferation and maturation of monocytes. At the same time, CD18 is crucial for the appropriate polarization and function of AAMs and tissue repair during chronic schistosomiasis.

Avaliação da qualidade de vida de pacientes renais crônicos submetidos à hemodiálise ­ casos da Santa Casa de Caridade de Diamantina / Quality of life assessment of chronic kidney patients undegoing hemodialysis ­ Cases of Santa Casa in caridade / Evaluación de la calidad de vida de los pacientes con insuficiencia renal crónica sometidos a hemodiálisis - casos de la Santa Casa de Caridade de Diamantina

Contexto: A doença renal crônica representa um sério problema de saúde pública, devido aos crescentes índices de morbimortalidade, e que associado à rotina de sessões de hemodiálise, promove alterações na qualidade de vida dos indivíduos com esta condição. Objetivo: Avaliar os fatores relacionados à qualidade de vida de pacientes renais crônicos em tratamento hemodialítico. Desenho e local: Estudo transversal, quantitativo, composto por 52 pacientes em hemodiálise no hospital Santa Casa de Caridade de Diamantina, Diamantina (MG), em 2017. Métodos: Foram utilizados dois questionários: socioeconômico-demográfico e o instrumento Kidney Disease and Quality of life Short Form. Os dados referentes à qualidade de vida foram analisados pelo programa elaborado e disponibilizado pelo Working Group. Resultados: Como fatores relacionados à baixa qualidade de vida foram encontrados: situação ocupacional (33,65 ± 26,71), peso da doença renal (49,28 ± 21,58), funcionamento físico (53,37 ± 22,39), saúde geral (54,71 ± 27,19) e função emocional (58,97 ± 26,23); em relação à boa qualidade de vida foram encontrados: função sexual (80,17 ± 22,46), função cognitiva (80,26 ± 35,32), satisfação do paciente (83,33 ± 20,51) e estímulo por parte da equipe de diálise (91,59 ± 29,17). Discussão: Por comparação aos trabalhos realizados em Goiânia (2006), Indaiatuba (2009), Mogi das Cruzes (2014) e ao presente estudo (2017) verificaram escores semelhantes na maioria das dimensões avaliadas, a exemplo das funções social e satisfação do paciente. Conclusão: A qualidade de vida apresentou-se como boa na maioria das dimensões avaliadas, entretanto, os fatores determinantes da baixa qualidade de vida reforçam a ideia da implementação de estratégias da equipe de saúde para melhorar a expectativa de vida desses pacientes.

Chronic kidney disease represents a serious public health problem, due to the increasing rates of morbidity and mortality, which, associated with the routine of hemodialysis sessions, promotes changes in the quality of life of individuals with this condition. Objective: To evaluate factors related to the quality of life of chronic renal patients undergoing hemodialysis. Design and location: Cross-sectional, quantitative study, composed of 52 hemodialysis patients at the Santa Casa de Caridade hospital in Diamantina, Diamantina (MG), in 2017. Methods: Two questionnaires were used: socioeconomic-demographic and the Kidney Disease and Quality of instrument life Short Form. Data on quality of life were analyzed using the program developed and made available by the Working Group. Results: As factors related to low quality of life were found: occupational situation (33.65 ± 26.71), weight of kidney disease (49.28 ± 21.58), physical functioning (53.37 ± 22.39), general health (54.71 ± 27.19) and emotional function (58.97 ± 26.23); in relation to good quality of life, sexual function (80.17 ± 22.46), cognitive function (80.26 ± 35.32), patient satisfaction (83.33 ± 20.51) and stimulation on the part were found of the dialysis team (91.59 ± 29.17). Discussion: Comparing the studies carried out in Goiânia (2006), Indaiatuba (2009), Mogi das Cruzes (2014) and the present study (2017) found similar scores in most of the dimensions evaluated, such as social functions and patient satisfaction. Conclusion: Quality of life was shown to be good in most of the dimensions evaluated, however, the determinants of low quality of life reinforce the idea of implementing health team strategies to improve the life expectancy of these patients.

Antecedentes: La enfermedad renal crónica representa un grave problema de salud pública, debido a las crecientes tasas de morbilidad y mortalidad, y la asociada a la rutina de sesiones de hemodiálisis, promueve cambios en la calidad de vida de los individuos con esta condición. Objetivo: Evaluar los factores relacionados con la calidad de vida de los pacientes renales crónicos en tratamiento hemodialítico. Diseño y entorno: Estudio transversal, cuantitativo, compuesto por 52 pacientes en hemodiálisis en el hospital Santa Casa de Caridade de Diamantina, Diamantina (MG), en 2017. Métodos: Se utilizaron dos cuestionarios: socioeconómico-demográfico y el instrumento Kidney Disease and Quality of life Short Form. Los datos relativos a la calidad de vida fueron analizados por el programa preparado y puesto a disposición por el Grupo de Trabajo. Resultados: Como factores relacionados con la baja calidad de vida se encontraron: la situación laboral (33,65 ± 26,71), la carga de la enfermedad renal (49,28 ± 21,58), el funcionamiento físico (53,37 ± 22,39), la salud general (54,71 ± 27,19) y la función emocional (58,97 ± 26,23); en relación con la buena calidad de vida se encontraron: la función sexual (80,17 ± 22,46), la función cognitiva (80,26 ± 35,32), la satisfacción del paciente (83,33 ± 20,51) y el estímulo del equipo de diálisis (91,59 ± 29,17). Discusión: En comparación con los estudios realizados en Goiânia (2006), Indaiatuba (2009), Mogi das Cruzes (2014) y el presente estudio (2017) se encontraron puntuaciones similares en la mayoría de las dimensiones evaluadas, como las funciones sociales y la satisfacción del paciente. Conclusión: La calidad de vida se presentó como buena en la mayoría de las dimensiones evaluadas, mientras que los factores determinantes de la baja calidad de vida refuerzan la idea de la implementación de estrategias del equipo de salud para mejorar las expectativas de vida de los pacientes.