Lipids, Gut Microbiota, and the Complex Relationship with Alzheimer's Disease: A Narrative Review.

Alzheimer's Disease (AD) is a multifactorial, progressive, and chronic neurodegenerative disorder associated with the aging process. Memory deficits, cognitive impairment, and motor dysfunction are characteristics of AD. It is estimated that, by 2050, 131.5 million people will have AD. There is evidence that the gastrointestinal microbiome and diet may contribute to the development of AD or act preventively. Communication between the brain and the intestine occurs through immune cells in the mucosa and endocrine cells, or via the vagus nerve. Aging promotes intestinal dysbiosis, characterized by an increase in pro-inflammatory pathogenic bacteria and a reduction in anti-inflammatory response-mediating bacteria, thus contributing to neuroinflammation and neuronal damage, ultimately leading to cognitive decline. Therefore, the microbiota-gut-brain axis has a significant impact on neurodegenerative disorders. Lipids may play a preventive or contributory role in the development of AD. High consumption of saturated and trans fats can increase cortisol release and lead to other chronic diseases associated with AD. Conversely, low levels of omega-3 polyunsaturated fatty acids may be linked to neurodegenerative diseases. Unlike other studies, this review aims to describe, in an integrative way, the interaction between the gastrointestinal microbiome, lipids, and AD, providing valuable insights into how the relationship between these factors affects disease progression, contributing to prevention and treatment strategies.

Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Alzheimer's disease (AD) comprises 60-70% of diagnosed dementia cases, and is characterized by the deposition of ß-amyloid peptide and the formation of neurofibrillary tangles of tau protein. Resveratrol is a neuroprotective agent acting in the prevention of redox impairment in addition to exerting anti-apoptotic actions on brain cells. An ability to reduce neuronal damage in patients with AD has been suggested by preclinical studies. OBJECTIVES: The aim of this systematic review was to investigate the evidence in the published literature from studies that evaluated the effects of supplementation with resveratrol, alone or in a solution with glucose and malate (RGM), on the functional and cognitive performance of patients with AD, as assessed by validated instruments. METHODS: A systematic literature search was performed in MEDLINE, CENTRAL, Embase, CINAHL, Web of Science, and Scopus databases including articles published up to August 2021. Randomized, placebo-controlled, clinical trials that reported cognitive and functional performance, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Cooperative Study of Alzheimer's Disease-Activities of Daily Living (ADCS-ADL), or the Mini Mental State Examination (MMSE), in AD patients treated with resveratrol, alone or as RGM, were included. RESULTS: After 1855 studies were identified, 24 RCTs underwent full-text review, with 20 studies excluded because they did not meet the inclusion criteria. Thus, four RCTs were included in the qualitative analyses. The findings demonstrate that there are still few studies in humans, but they showed that this polyphenol acts in the delay of cognitive impairment in patients with AD, when administered alone or in combination with glucose and malate. CONCLUSIONS: Supplementation with resveratrol seems to influence the progressive cognitive and functional decline in AD patients, when compared with a placebo group. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021229234.

Do Genetic Polymorphisms Affect Fetal Hemoglobin (HbF) Levels in Patients With Sickle Cell Anemia Treated With Hydroxyurea? A Systematic Review and Pathway Analysis.

Hydroxyurea has long been used for the treatment of sickle cell anemia (SCA), and its clinical effectiveness is related to the induction of fetal hemoglobin (HbF), a major modifier of SCA phenotypes. However, there is substantial variability in response to hydroxyurea among patients with SCA. While some patients show an increase in HbF levels and an ameliorated clinical condition under low doses of hydroxyurea, other patients present a poor effect or even develop toxicity. However, the effects of genetic polymorphisms on increasing HbF levels in response to hydroxyurea in patients with SCA (Hb SS) have been less explored. Therefore, we performed a systematic review to assess whether single-nucleotide polymorphisms (SNPs) affect HbF levels in patients with SCA treated with hydroxyurea. Moreover, we performed pathway analysis using the set of genes with SNPs found to be associated with changes in HbF levels in response to hydroxyurea among the included studies. The systematic literature search was conducted on Medline/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science. Seven cohort studies were included following our inclusion and exclusion criteria. From the 728 genetic polymorphisms examined in the included studies, 50 different SNPs of 17 genes were found to be associated with HbF changes in patients with SCA treated with hydroxyurea, which are known to affect baseline HbF but are not restricted to them. Enrichment analysis of this gene set revealed reactome pathways with the lowest adjusted p-values and highest combined scores related to VEGF ligand-receptor interactions (R-HSA-194313; R-HSA-195399) and the urea cycle (R-HSA-70635). Pharmacogenetic studies of response to hydroxyurea therapy in patients with SCA are still scarce and markedly heterogeneous regarding candidate genes and SNPs examined for association with HbF changes and outcomes, suggesting that further studies are needed. The reviewed findings highlighted that similar to baseline HbF, changes in HbF levels upon hydroxyurea therapy are likely to be regulated by multiple loci. There is evidence that SNPs in intron 2 of BCL11A affect HbF changes in response to hydroxyurea therapy, a potential application that might improve the clinical management of SCA. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=208790).

The Role of the Mediterranean Dietary Pattern on Metabolic Control of Patients with Diabetes Mellitus: A Narrative Review.

Diabetes mellitus (DM) is a metabolic disorder characterised by hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism. Several studies demonstrated that foods typical of the Mediterranean diet (MedDiet), including vegetables, fruits, oilseeds, extra virgin olive oil and fish, can promote health benefits for individuals at risk of or with type 2 diabetes (T2DM). In this review, we summarised randomised clinical trials, cohort studies, meta-analyses and systematic reviews that evaluated the effects of the MedDiet on metabolic control of T2DM. The data suggest that the MedDiet influences cardiovascular risk factors, including blood pressure, lipid profile, insulin resistance, inflammation and glucose metabolism, in T2DM patients. In conclusion, the MedDiet appears to protect patients from macro- and microangiopathy and should be considering in the management of diabetic patients.

microRNAs associated to anthracycline-induced cardiotoxicity in women with breast cancer: A systematic review and pathway analysis.

BACKGROUND: Cardiotoxicity is a common and serious adverse effect of anthracycline therapy in breast cancer patients. The current criteria for cardiotoxicity are based on imaging and cardiac biomarkers. However, there is a need for new biomarkers to help with early diagnosis. MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in the regulation of gene expression. Several miRNAs have been associated with cardiovascular diseases and are biomarkers under investigation for cancer treatment-related cardiotoxicity. METHODS: We performed a systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Web of Science and Embase, until April 2020. Cohort studies that reported miRNA biomarkers in breast cancer patients with anthracycline-induced cardiotoxicity and non-cardiotoxicity patients were included. Moreover, we searched the miRTarBase for experimentally validated miRNA-target interactions. RESULTS: Among the 209 studies retrieved, five fulfilled the inclusion criteria. Let-7f, miR-1, miR-20a, miR-126 and miR-210 were validated in two population-based cohorts. The pro-angiogenic miRNAs let-7f, miR-20a, miR-126 and miR-210 were significantly down-regulated in epirubicin-cardiotoxicity when compared to the non-cardiotoxicity group. miR-1 has been shown to provide diagnostic and prognostic information in the setting of myocardial infarction, but changes in its levels are controversial in doxorubicin-treated breast cancer patients with cardiotoxicity. Reactome pathways relevant to cardiotoxicity were found from the target genes for let-7f, miR-1, miR-20a, miR-126 and miR-210 at miRTarBase. CONCLUSION: The data suggest that let-7f, miR-1, miR-20a, miR-126 and miR-210 are associated with anthracycline-based cardiotoxicity during chemotherapy in breast cancer patients.

Determination of glycemic index of enteral formulas used in clinical practice.

Glycemic Index (GI) is a measure of carbohydrate quality and is recognised as a valid and reproducible method of classifying carbohydrate foods according to its effects on postprandial glycaemia. In this randomised crossover trial (RBR-7rjx3k) we determined the GI of nine enteral formulas, following the Food and Agriculture Organisation/World Health Organisation method. Forty healthy participants were included in the study (85% female mean age 27.1 ± 6.7 years). GI of the enteral formulas ranged from 40.5 to 85.2; four formulas had high GI (Nutrienteral 1.5®, Novasource GI Control®, Diamax®, Isosource Soya®), two intermediate GI (Fresubin 1.2 HP Fibre®, Nutrison Energy Multifiber 1.5®) and three low GI (Trophic 1.5®, Glucerna®, Novasource GC HP®). The GI coefficient of variation ranged from 22.9% to 83.6%. The effect of the enteral formulas with low GI in glycemic control of patients with enteral nutrition prescription needs to be test in future studies.

Subjective Global Assessment Can Be Performed in Critically Ill Surgical Patients as a Predictor of Poor Clinical Outcomes.

BACKGROUND: There is limited evidence on the applicability of subjective global assessment (SGA) in critically ill patients, despite its good performance in diagnosing undernutrition in clinical and surgical patients. Our aim was to evaluate the association between SGA and anthropometric measures and the performance of SGA in predicting clinical outcomes and mortality in critically ill surgical patients. METHODS: This observational prospective study was carried out with patients admitted to the surgical intensive care unit (SICU) of a Brazilian hospital. Nutrition assessment comprised anthropometric measures (weight and height for body mass index [BMI] calculation, mid-arm circumference [MAC] and calf circumference [CC]), and the SGA. Patients were followed up until hospital discharge for measurement of the following outcomes: length of stay (LOS), SICU LOS, and hospital mortality. RESULTS: This study included 76 surgical patients admitted to an SICU (64.9% males; 87% white ethnicity; mean age, 60.36 ± 16.24 years). According to the SGA, the prevalence of undernutrition was 60.5% (moderate undernutrition = 38.2%; severe undernutrition = 22.4%), and well-nourished 39.0%. Patients with severe undernutrition had lower values of current weight, BMI, MAC, and CC compared with well-nourished patients. The presence of undernutrition increased the risk of LOS >31 days by 2.57 (1.38-4.77) times, but it was not associated with mortality. CONCLUSIONS: Patients with severe undernutrition had lower current weight, BMI, MAC, and CC compared with well-nourished patients. Undernutrition did not increase the risk of death; however, it did increase the relative risk for a longer hospital stay by 2.5.