Correlation between Genomic Variants and Worldwide COVID-19 Epidemiology.

COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved over time with distinct transmissibility subvariants from ancestral lineages. The clinical manifestations of the disease vary according to their severity and can range from asymptomatic to severe. Due to the rapid evolution to a pandemic, epidemiological studies have become essential to understand and effectively combat COVID-19, as the incidence and mortality of this disease vary between territories and populations. This study correlated epidemiological data on the incidence and mortality of COVID-19 with frequencies of important SNPs in GWAS studies associated with the susceptibility and mortality of this disease in different populations. Our results indicated significant correlations for 11 genetic variants (rs117169628, rs2547438, rs2271616, rs12610495, rs12046291, rs35705950, rs2176724, rs10774671, rs1073165, rs4804803 and rs7528026). Of these 11 variants, 7 (rs12046291, rs117169628, rs1073165, rs2547438, rs2271616, rs12610495 and rs35705950) were positively correlated with the incidence rate, these variants were more frequent in EUR populations, suggesting that this population is more susceptible to COVID-19. The rs2176724 variant was inversely related to incidence rates; therefore, the higher the frequency of the allele is, the lower the incidence rate. This variant was more frequent in the AFR population, which suggests a protective factor against SARS-CoV-2 infection in this population. The variants rs10774671, rs4804803, and rs7528026 showed a significant relationship with mortality rates. SNPs rs10774671 and rs4804803 were inversely related to mortality rates and are more frequently present in the AFR population. The rs7528026 variant, which is more frequent in the AMR population, was positively related to mortality rates. The study has the potential to identify and correlate the genetic profile with epidemiological data, identify populations that are more susceptible to severe forms of COVID-19, and relate them to incidence and mortality.

Brain and serum lipidomic profiles implicate Lands cycle acyl chain remodeling association with APOEε4 and mild cognitive impairment.

Introduction: At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (ε4) in a cholesterol and phospholipid transporter, Apolipoprotein E (APOEε4), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD. Methods: We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis. Results: Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and APOEε4 carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired APOEε4 carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-ß (Aß) load and tau tangle pathologies. Discussion: Our studies highlight the critical differences in acyl chain remodeling in brain tissue from APOEε4 carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both APOEε4 carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention.

Standardization use of the international classification of functioning, disability and health in the determination of health status in patients with post-acute COVID-19 syndrome.

PURPOSE: To propose a standardized method for the use of the International Classification of Functioning, Disability and Health (ICF) to describe the health status in Post-Acute COVID-19 Syndrome (PACS) and investigate interrater agreement in the linking process in instruments and clinical exams using the ICF categories. MATERIALS AND METHODS: Cross-sectional and interrater agreement study that followed the Guidelines for Reporting Reliability and Agreement Studies. Two raters performed the linking coding process in instruments of quality of life, anxiety and depression, fatigue and pulmonary function, inspiratory muscle strength and cardiopulmonary exercise testing. The codes were qualified by standards defined to each instrument and exams. RESULTS: The instrument with the lowest Cohen's Kappa coefficient was anxiety and depression (k = 0.57). Forty ICF codes were linked to clinical instruments and exams. The fatigue instrument presented a higher degree of disability by the qualification process, from severe to complete, in the linked codes. CONCLUSION: The study presents a standardized method for the assessment of the health status of patients with PACS through ICF. Restriction in work performance, socialization and family relationships as well as disabilities in physical endurance, fatigue and exercise tolerance were found in the sample. The agreement between the raters was moderate to perfect, demonstrating that the method can be reproducible.

The body structures and functions, environmental factors, activities and participation in a person's environment are determinant aspects of his health.Ways to measure these aspects are key to assessing health not only as absence of disease, so the International Classification of Disability and Functional Health demonstrates the ability to fully describe health.This study proposes a standardization in the use of the tool to facilitate usability in clinical practice.

Orange passion fruit (Passiflora caerulea L.) as a new raw material for acetic fermentation: evaluation of organic acids and phenolic profile, in vitro digestion, and biological activities.

BACKGROUND: This study evaluated for the first time the potential of orange passion fruit as a base for alcoholic and acetic fermentations, with a view to assessing its profile of organic acids and polyphenols, in vitro digestion, and biological activities. RESULTS: In terms of aliphatic organic acids, malic acid was the majority in the wine (3.19 g L-1), while in the vinegar, it was acetic acid (46.84 g L-1). 3,4-Dihydroxybenzoic acid (3,4-DHB) was the major phenolic compound in the wine and vinegar samples (3443.93 and 2980.00 µg L-1, respectively). After the in vitro gastrointestinal simulation stage, the wine showed high bioaccessibility for the compounds sinipaldehyde (82.97%) and 2,4-dihydroxybenzoic acid (2,4-DHBA, 81.27%), while the vinegar exhibited high bioaccessibility for sinipaldehyde (89.39%). Through multivariate analysis, it was observed that 3,4-DHB was highly concentrated in the different digested fractions obtained from the wine. In contrast, in the vinegar, the stability of isorahmenetin and Quercetin 3-o-rhamnoside was observed during the in vitro digestion simulation. Lastly, the vinegar stood out for its inhibition rates of α-amylase (23.93%), α-glucoside (18.34%), and angiotensin-converting enzyme (10.92%). In addition, the vinegar had an inhibitory effect on the pathogenic microorganisms Salmonella enteritidis, Escherichia coli, and Listeria monocytogenes. CONCLUSION: Orange passion fruit has proved to be a promising raw material for the development of fermented beverages. Therefore, this study provides an unprecedented perspective on the use and valorization of orange passion fruit, contributing significantly to the advancement of knowledge about fermented products and the associated nutritional and functional possibilities. © 2024 Society of Chemical Industry.

Non-hemorrhagic imaging markers of cerebral amyloid angiopathy in memory clinic patients.

INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35). DISCUSSION: Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. HIGHLIGHTS: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.

Investigating the correlation between genotype and phenotype in Prader-Willi syndrome: a study of 45 cases from Brazil.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis. RESULTS: We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles. CONCLUSIONS: The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study's findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS.

[Program for Integral Assistance to Women's Health, 40 years of history: interview with Ana Maria Costa]. / Programa de Assistência Integral à Saúde da Mulher, 40 anos de uma história: entrevista com Ana Maria Costa.

The interview marks the 40th anniversary of the Programa de Assistência Integral à Saúde da Mulher (Program for Integral Assistance to Women's Health), and aims to revisit the history of this innovative health policy, the context in which it was created and the generation that took it forward, from the narrative of a key person, Ana Maria Costa, who played a leading role in the process of its creation, from conception to the elaboration of its final text. Launched in 1983, the policy was a pioneer in proposing and incorporating the principles of universality, equity and integrality, which would be the foundations of the Sistema Único de Saúde, and introducing the perspective of women's reproductive rights.

A entrevista marca os 40 anos do Programa de Assistência Integral à Saúde da Mulher e tem como objetivo revisitar a história dessa política de saúde inovadora, do contexto em que foi criada e da geração que a levou adiante, a partir da narrativa de uma pessoa-chave, Ana Maria Costa, que protagonizou o processo de sua criação, desde a concepção até a elaboração de seu texto final. Lançada em 1983, a política foi pioneira em propor e incorporar os princípios de universalidade, equidade e integralidade, que seriam os fundamentos do Sistema Único de Saúde, e introduzir a perspectiva dos direitos reprodutivos das mulheres.

Abundance of Leishmania (Kinetoplastida: Trypanosomatidae) vectors in Baldim, a municipality in the Espinhaço Range Biosphere Reserve in Brazil.

Leishmaniasis is a zoonoses caused by protozoan parasites belonging to the Leishmania genus that is transmitted to humans through the bite of previously infected phlebotomine sandflies (Diptera:Psychodidae:Phlebotominae). In Brazil, 2 types of leishmaniasis are endemic, tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL). In Baldim, a municipality in the Espinhaço Range Biospere Reserve (ERBR), 5 autochthonous cases of TL, and one autochthonous case of VL were reported from 2017 to 2022. Owing to the lack of data on entomological fauna, we surveyed the occurrence and distribution of phlebotomine sandflies that could act as Leishmania vectors, as well as natural Leishmania infection. During 1 year, 918 sandfly specimens belonging to 12 species were collected. The predominant species was Lutzomyia longipalpis (Lutz & Neiva, 1912) (32.0%), a proven VL agent, followed by Evandromyia evandroi (Costa Lima & Antunes, 1936) (20.7%), Evandromyia cortelezzii (Brèthes, 1923) (17.0%), Nyssomyia whitmani (Antunes & Coutinho, 1939) (12.2%), and Nyssomyia intermedia (Lutz & Neiva, 1912) (10.5%), all putative or proven TL agents. Seasonal fluctuations and endo-exophilic behavior were delineated for the main phlebotomine sandflies. The population of Lu. longipalpis was higher during the coolest and driest months, although different profiles were noted for the other species. Natural Leishmania infection was not detected in any of the 197 phlebotomine sandfly females analyzed. The results were compared with those previously obtained in other municipalities belonging to the ERBR. The presence of Leishmania vectors and human cases of leishmaniasis indicate a risk of Leishmania transmission in the region.

Cellulose acetate scaffold coated with a hydroxyapatite/graphene oxide nanocomposite for application in tissue engineering.

The objective of this study was to synthesize and characterize porous Cellulose Acetate (CA) scaffolds using the electrospinning technique and functionalize the surface of the scaffolds obtained through the dip-coating method with a Hydroxyapatite (HA) nanocomposite and varying concentrations of graphene oxide (GO) for application in tissue engineering regeneration techniques. The scaffolds were divided into four distinct groups based on their composition: 1) CA scaffolds; 2) CAHAC scaffolds; 3) CAHAGOC 1.0% scaffolds; 4) CAHAGOC 1.5% scaffolds. Scaffold analyses were conducted using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy, Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS), and in vitro cell viability assays (WST). For the biological test analysis, Variance (two-way) was used, followed by Tukey's post-test (α = 0.05). The XRD results revealed the predominant presence of CaP phases in the CAHAC, CAHAGOC 1.0%, and CAHAGOC 1.5% groups, emphasizing the presence of HA in the scaffolds. FTIR demonstrated characteristics of cellulose and PO4 bands in the groups containing HA, confirming the presence of CaP in the synthesized materials, as also indicated by XRD. Raman spectroscopy showed the presence of D and G bands, consistent with GO, confirming the successful incorporation of the HAGO nanocomposite into the scaffolds. The micrographs displayed overlapping electrospun fibers, forming the three-dimensional structure in the produced scaffolds. It was possible to observe hydroxyapatite crystals filling some of these pores, creating a suitable structure for cell adhesion, proliferation, and nutrition, as corroborated by the results of in vitro tests. All scaffolds exhibited high cell viability, with significant cell proliferation. Even after 48 h, there was a slight reduction in the number of cells, but a noteworthy increase in cell proliferation was evident in the CAHAGOC 1.5% group after 48 h (p < 0.05). In conclusion, it can be affirmed that the produced scaffolds demonstrated physical and biological characteristics and properties capable of promoting cell adhesion and proliferation. Therefore, they represent significant potential for application in tissue engineering, offering a new perspective regarding techniques and biomaterials applied in regenerative therapies.

Histological biomarkers and microbiological parameters of an estuarine fish from the Brazilian Amazon coast as potential indicators of risk to human health.

This study aimed to isolate and identify pathogenic bacteria in the intestinal tract, skin, and muscles of Sciades herzbergii; detect histopathological changes in the gill and liver; and use these biomarkers for the assessment of potential risks to human health. Fish were sampled during the rainy and dry seasons at two points in São Marcos Bay, Maranhão, Brazil: Ilha dos Caranguejos (IC) and Porto Grande (PG). Isolation and quantification were carried out using COLItest®. Colonies were subjected to identification and phenotypic investigation of antimicrobial resistance using Vitek®. Gill and liver samples were subjected to routine histological examination. The results indicated the presence of Klebsiella pneumoniae and Escherichia coli, the latter of which showed phenotypic resistance to norfloxacin and gentamicin. Fish caught at PG exhibited more extensive gill and liver damage than fish caught at IC. The findings suggest that histological changes in target organs of S. herzbergii may be influenced by infection with pathogenic bacteria.

An open computational toolbox to analyze multi- and single-unit sympathetic nerve activity in microneurography.

Microelectrode recordings from human peripheral and cranial nerves provide a means to study both afferent and efferent axonal signals at different levels of detail, from multi- to single-unit activity. Their analysis can lead to advancements both in diagnostic and in the understanding of the genesis of neural disorders. However, most of the existing computational toolboxes for the analysis of microneurographic recordings are limited in scope or not open-source. Additionally, conventional burst-based metrics are not suited to analyze pathological conditions and are highly sensitive to distance of the microelectrode tip from the active axons. To address these challenges, we developed an open-source toolbox that offers advanced analysis capabilities for studying neuronal reflexes and physiological responses to peripheral nerve activity. Our toolbox leverages the observation of temporal sequences of action potentials within inherently cyclic signals, introducing innovative methods and indices to enhance analysis accuracy. Importantly, we have designed our computational toolbox to be accessible to novices in biomedical signal processing. This may include researchers and professionals in healthcare domains, such as clinical medicine, life sciences, and related fields. By prioritizing user-friendliness, our software application serves as a valuable resource for the scientific community, allowing to extract advanced metrics of neural activity in short time and evaluate their impact on other physiological variables in a consistent and standardized manner, with the final aim to widen the use of microneurography among researchers and clinicians.

Influence of morbidity, early nutritional intake, and total energy: protein ratio on longitudinal extrauterine growth restriction of very preterm newborns at term-equivalent age: an observational study.

To evaluate the influence of early nutritional intake on the growth pattern of very preterm infants. This was an observational study including 109 newborns (< 32 weeks gestational age). Perinatal morbidities, nutritional therapy (first four weeks of life), and weight, length, and head circumference (HC) growth at term-equivalent age were evaluated. Growth restriction was defined as a difference > 1.2 SD between the birth and term age measurements. Growth restriction at term-equivalent age: 52.3% (weight), 42.9% (length), and 22% (HC). Morbidities were positively correlated with nutrition therapy and negatively correlated with the total energy provision: protein ratio. The duration of parenteral nutrition, the time to reach full enteral feedings, and the total energy provision: protein ratio were significantly correlated. Nutrient intake influenced weight, length, and HC growth, and cumulative energy deficit was significantly associated with HC growth restriction.   Conclusion: Perinatal morbidities interfere with nutritional therapy and early nutrient intake, leading to insufficient energy and energy provision: protein ratio for growth. What is Known: • The intake of macronutrients early in life, mainly protein, is important for the optimal growth of pretem infants. • The severity of morbidities and low gestational ages impact the nutritional management of preterm infants. What is New: • The number of morbidities, reflecting the severity of the neonatal clinical course, had a detrimental effect on the nutritional therapy and nutrients intake. • The inadequate energy provision per gram of protein ratio was significantly associated with growth restriction in all growth measures at the second week of life, persisting for head circumference up to the fourth week, highlighting the importance of its measurement, as it could be a precocious sign of development risk.

Optimization of Biodiesel Production Process Using MoO3 Catalysts and Residual Oil: A Comprehensive Experimental 23 Study.

The study aimed to utilize MoO3 catalysts, produced on a pilot scale via combustion reaction, to produce biodiesel from residual oil. Optimization of the process was conducted using a 23 experimental design. Structural characterization of the catalysts was performed through X-ray diffraction, fluorescence, Raman spectroscopy, and particle size distribution analyses. At the same time, thermal properties were examined via thermogravimetry and differential thermal analysis. Catalytic performance was assessed following process optimization. α-MoO3 exhibited a monophasic structure with orthorhombic phase, whereas α/h-MoO3 showed a biphasic structure. α-MoO3 had a larger crystallite size and higher crystallinity, with thermal stability observed up to certain temperatures. X-ray fluorescence confirmed molybdenum oxide predominance in the catalysts, with traces of iron oxide. Particle size distribution analyses revealed polymodal distributions attributed to structural differences. Both catalysts demonstrated activity under all conditions tested, with ester conversions ranging from 93% to 99%. The single-phase catalyst had a long life cycle and was reusable for six biodiesel production cycles. The experimental design proved to be predictive and significant, with the type of catalyst being the most influential variable. Optimal conditions included α-MoO3 catalyst, oil/alcohol ratio of 1/15, and a reaction time of 60 min, resulting in high biodiesel conversion rates and showcasing the viability of MoO3 catalysts in residual oil biodiesel production.

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population.

Radiotherapy is focused on the tumor but also reaches healthy tissues, causing toxicities that are possibly related to genomic factors. In this context, radiogenomics can help reduce the toxicity, increase the effectiveness of radiotherapy, and personalize treatment. It is important to consider the genomic profiles of populations not yet studied in radiogenomics, such as the indigenous Amazonian population. Thus, our objective was to analyze important genes for radiogenomics, such as ATM, TGFB1, RAD51, AREG, XRCC4, CDK1, MEG3, PRKCE, TANC1, and KDR, in indigenous people and draw a radiogenomic profile of this population. The NextSeq 500® platform was used for sequencing reactions; for differences in the allelic frequency between populations, Fisher's Exact Test was used. We identified 39 variants, 2 of which were high impact: 1 in KDR (rs41452948) and another in XRCC4 (rs1805377). We found four modifying variants not yet described in the literature in PRKCE. We did not find any variants in TANC1-an important gene for personalized medicine in radiotherapy-that were associated with toxicities in previous cohorts, configuring a protective factor for indigenous people. We identified four SNVs (rs664143, rs1801516, rs1870377, rs1800470) that were associated with toxicity in previous studies. Knowing the radiogenomic profile of indigenous people can help personalize their radiotherapy.

Aging-dependent mitochondrial bioenergetic impairment in the skeletal muscle of NNT-deficient mice.

Overall health relies on features of skeletal muscle that generally decline with age, partly due to mechanisms associated with mitochondrial redox imbalance and bioenergetic dysfunction. Previously, aged mice genetically devoid of the mitochondrial NAD(P)+ transhydrogenase (NNT, encoded by the nicotinamide nucleotide transhydrogenase gene), an enzyme involved in mitochondrial NADPH supply, were shown to exhibit deficits in locomotor behavior. Here, by using young, middle-aged, and older NNT-deficient (Nnt-/-) mice and age-matched controls (Nnt+/+), we aimed to investigate how muscle bioenergetic function and motor performance are affected by NNT expression and aging. Mice were subjected to the wire-hang test to assess locomotor performance, while mitochondrial bioenergetics was evaluated in fiber bundles from the soleus, vastus lateralis and plantaris muscles. An age-related decrease in the average wire-hang score was observed in middle-aged and older Nnt-/- mice compared to age-matched controls. Although respiratory rates in the soleus, vastus lateralis and plantaris muscles did not significantly differ between the genotypes in young mice, the rates of oxygen consumption did decrease in the soleus and vastus lateralis muscles of middle-aged and older Nnt-/- mice. Notably, the soleus, which exhibited the highest NNT expression level, was the muscle most affected by aging, and NNT loss. Additionally, histology of the soleus fibers revealed increased numbers of centralized nuclei in older Nnt-/- mice, indicating abnormal morphology. In summary, our findings suggest that NNT expression deficiency causes locomotor impairments and muscle dysfunction during aging in mice.

Circadian ABCG2 Expression Influences the Brain Uptake of Donepezil across the Blood-Cerebrospinal Fluid Barrier.

Donepezil (DNPZ) is a cholinesterase inhibitor used for the management of Alzheimer's disease (AD) and is dependent on membrane transporters such as ABCG2 to actively cross brain barriers and reach its target site of action in the brain. Located in the brain ventricles, the choroid plexus (CP) forms an interface between the cerebrospinal fluid (CSF) and the bloodstream, known as the blood-CSF barrier (BCSFB). Historically, the BCSFB has received little attention as a potential pathway for drug delivery to the central nervous system (CNS). Nonetheless, this barrier is presently viewed as a dynamic transport interface that limits the traffic of molecules into and out of the CNS through the presence of membrane transporters, with parallel activity with the BBB. The localization and expression of drug transporters in brain barriers represent a huge obstacle for drug delivery to the brain and a major challenge for the development of therapeutic approaches to CNS disorders. The widespread interest in understanding how circadian clocks modulate many processes that define drug delivery in order to predict the variability in drug safety and efficacy is the next bridge to improve effective treatment. In this context, this study aims at characterizing the circadian expression of ABCG2 and DNPZ circadian transport profile using an in vitro model of the BCSFB. We found that ABCG2 displays a circadian pattern and DNPZ is transported in a circadian way across this barrier. This study will strongly impact on the capacity to modulate the BCSFB in order to control the penetration of DNPZ into the brain and improve therapeutic strategies for the treatment of AD according to the time of the day.

Gastrointestinal bleeding in patients with COVID-19: an integrative review.

INTRODUCTION: In 2020, the world suffered a major impact from the COVID-19 pandemic, especially due to the high transmissibility of the virus. It is a disease that predominates with respiratory manifestations, but there is involvement of the gastrointestinal tract, causing symptoms ranging from mild to more severe. Highlighting gastrointestinal bleeding, it is a symptom resulting from the involvement of the SARS-CoV-2 virus described by several reports and case series. METHODS: through an integrative literature review, of a qualitative nature, works that corresponded to the eligibility criteria were selected, totaling 16 articles included in this review. RESULTS: of the patients who manifested gastrointestinal symptoms associated with the disease, common comorbidities and clinical manifestations were identified, in addition to therapies used to treat the infection, which were predisposing factors for the development of gastrointestinal bleeding. CONCLUSION: The presence of gastrointestinal bleeding in patients with COVID-19 is established in the literature, since the pathophysiological mechanisms of the disease directly affect the GIT. Early recognition of symptoms and suspicion of gastrointestinal involvement allows better management of patients and complications.

Cost-effectiveness analysis of a cardio-oncology rehabilitation framework compared to an exercise intervention for cancer survivors with high cardiovascular risk.

BACKGROUND: A cardio-oncology rehabilitation model among cancer survivors showed superior results comparing to a community-based exercise intervention. However, questions remain about its cost-effectiveness. AIMS: To assess the cost-effectiveness of a center-based cardiac rehabilitation (CBCR) program when compared to usual care encompassing a community-based exercise training (CBET), among cancer survivors with high cardiovascular risk. METHODS: The CORE study was a single-center, prospective, randomized controlled trial; 80 adult cancer survivors with previous exposure to cardiotoxic cancer treatment and/or with previous cardiovascular disease were assigned (1:1 ratio) to an 8-week CBCR or CBET, twice/week. Cost-effectiveness was a pre-specified secondary endpoint. Outcomes included healthcare resource use and costs, quality-adjusted life-years (QALYs) and cost-effectiveness; incremental cost-effectiveness ratio (ICER) was computed from a societal perspective. RESULTS: 75 patients completed the study (CBCR N=38; CBET N=37). The CBCR had significantly higher cost per patient (477.76 ± 39.08€) compared to CBET group (339.32 ± 53.88€), with a significant between-group difference 138.44€ (95% CI, 116.82 to 160.05€, p<0.01). A between-group difference by 0.100 points in QALYs was observed, favouring the CBCR (95% CI, -0.163 to -0.037, p=0.002). When CBCR was compared with CBET, the ICER was €1,383.24 per QALY gained; at a willingness-to-pay threshold of €5,000 per QALY, the probability of CBCR being cost-effective was 99.9% (95% CI, 99.4 to 100.0). CONCLUSION: The CORE trial shows that a CBCR is a cost-effective intervention in the management of cancer survivors with high cardiovascular risk, reinforcing the potential benefits of this multidisciplinary approach in supportive care of this specific subset of cancer patients.

The CORE study was a randomized clinical trial including 80 cancer survivors with high cardiovascular risk; an 8-week cardio-oncology rehabilitation framework promoted superior results on cardiorespiratory fitness (peak oxygen consumption) and quality of life, but questions remained about the cost-effectiveness of this option. This study findings suggest that: a center-based cardiac rehabilitation proved to be cost-effective, when compared to usual care encompassing community-based exercise training the value-added of a comprehensive approach delivered in an oncological setting reinforce the potential benefits of including this intervention in supportive care of a specific subset of cancer patients, within existing contemporary cardiac rehabilitation resources and infrastructures.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

Adherence to the Mediterranean Diet, Sodium and Potassium Intake in People at a High Risk of Dementia.

Adequate sodium and potassium intake, along with adherence to the Mediterranean diet (MedDiet), are key factors for preventing hypertension and cerebrovascular diseases. However, data on the consumption of these nutrients within the MedDiet are scarce. This cross-sectional study aims to assess the association between MedDiet adherence and sodium/potassium intake in the MIND-Matosinhos randomized controlled trial, targeting Portuguese adults at a high risk of dementia. Good adherence to the MedDiet was defined using the Portuguese Mediterranean Diet Adherence Screener questionnaire (≥10 points), and both sodium/potassium intakes were estimated from 24-hour urine collections. The association between MedDiet adherence and these nutrients' intake (dichotomized by the median) was quantified by calculating odds ratios (OR) and respective 95% confidence intervals (95% CI) using a logistic regression. A total of 169 individuals (60.9% female; median age: 70 years; range: 36-85 years) were included. Good adherence to the MedDiet was observed among 18.3% of the sample. After adjusting for sex, age, education and using antihypertensive drugs, good MedDiet adherence was associated with higher sodium (OR = 3.11; 95% CI: 1.27-7.65) and potassium intake (OR = 9.74; 95% CI: 3.14-30.26). Increased adherence to the MedDiet may contribute to a higher potassium intake but seems to have limited effects on the adequacy of sodium levels.