MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training.

Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.

Local trade, spatial occurrence and conservation of hypostomus soniae (siluriformes, loricariidae), an ornamental fish endemic to the tapajos river, Brazil.

Hypostomus soniae is a small sized armored catfish endemic to the Tapajos River basin and ranked as one of the most exploited ornamental fish in the Santarem export marketplace. This study aims to evaluate distributional patterns of Hypostomus soniae and contribute to the species conservation in the face of development of the ornamental fish trade in the Amazon region. We compiled data associated with geographic coordinates in public repositories, supplemented with original field records. We compared our data to published records in the literature and museum collections to check for accuracy. To investigate the fishery and commercialization of H. soniae, we conducted interviews with ornamental fish stakeholders from the local trade. We also made direct observations in the fishing sites and export facilities in Santarem. A cluster analysis of the geolocation data was carried out to explore the spatial distribution patterns. The volume of captures and exportation of H. soniae decreased during the period 2020-2023. The occurrence of H. soniae was associated with annual rainfall ranging from 2,000 mm to 2,500 mm and concentrated in two municipalities of the State of Mato Grosso and two of the Para State. The species distribution area has been threatened, unfortunately, by fishermen who do not respect the laws that support artisanal fishing in the Amazon.

An African moral approach against the perverted faculty argument: Ukama, partiality and homophobia in Africa.

In Africa, homosexuality is routinely understood as a form of immoral behaviour. This has great implications for the physical and psychological well-being of homosexuals in Africa. One of the reasons why homosexuals are sometimes understood to be behaving immorally is because it is believed that same-sex relations are unnatural. I think that this conception of unnatural is grounded on the perverted faculty argument, although this is not often expressed in such terms. In this article, I will develop a concept of natural grounded on the concept of Ukama. I will show that despite Ukama implying a functional conception of nature, just like in the perverted faculty argument, it does not imply that homosexuality is immoral.

Addressing exploitation and inequities in open science: A relational perspective.

There are concerns that participation in open science will lead to various forms of exploitation - of researchers and scholars in low-income countries and under-resourced institutions. This article defends a contrary thesis and demonstrates the exact ways the underexplored notions of communal relationships, human dignity and social justice - and the normative principles to which they give rise - grounded in African philosophy can usefully address critical concerns regarding exploitation in the sharing of research resources to facilitate open partnership/collaboration and reuse. Further research is required to study the specific roles different institutions can play in facilitating open practice and contribute towards establishing effective structures that can enhance equity and balance unfavourable power asymmetries.

A Sino-African perspective and the morality of procreation.

Current studies of anti/-natalism have been carried out mainly in the context of western philosophy. In this article, we offer a pro-natalist view based on Confucian and Afro-communitarian philosophy (Sino-African ethics). Grounded in this Sino-African perspective, we uphold that there is, at least, one reason to believe that not only is it morally permissible to procreate, but also that on some occasions, procreating is what morality prescribes. Specifically, we contend that, from a Sino-African perspective, procreating sometimes is the best way to fulfil duties of reciprocity and care towards our parents.

Anticancer Activity of Chalcones and Its Derivatives: Review and In Silico Studies.

Chalcones are direct precursors in the biosynthesis of flavonoids. They have an α,ß-unsaturated carbonyl system which gives them broad biological properties. Among the biological properties exerted by chalcones, their ability to suppress tumors stands out, in addition to their low toxicity. In this perspective, the present work explores the role of natural and synthetic chalcones and their anticancer activity in vitro reported in the last four years from 2019 to 2023. Moreover, we carried out a partial least square (PLS) analysis of the biologic data reported for colon adenocarcinoma lineage HCT-116. Information was obtained from the Web of Science database. Our in silico analysis identified that the presence of polar radicals such as hydroxyl and methoxyl contributed to the anticancer activity of chalcones derivatives. We hope that the data presented in this work will help researchers to develop effective drugs to inhibit colon adenocarcinoma in future works.

Justifying a morally permissible breach of contract: kantian ethics, nozickian justice, and vaccine patents.

Although some have argued that COVID-19 vaccine patents are morally justified, a broader argument on the morality of breaching contracts is necessary. This article explores the ethics of breaching unfair contracts and argues that it is morally justified to breach contracts with pharmaceutical companies concerning vaccine patents. I offer two arguments to support this view. Firstly, contracts may be breachable in some situations. The ones I point out are that contracts can be broken when the costs of not violating vaccine patents are too high or when the process for agreement is not fair, or when an urgent ethical issue needs to be addressed and it is possible to compensate the other party for their loss. Secondly, I argue that because the contracts with the pharmaceutical companies do not treat people as ends in themselves, there is no moral obligation to respect them.

The type of SARS-CoV-2 vaccine influences serological response in kidney transplant recipients.

Vaccination is a promising strategy to control the ongoing pandemic; however, solid organ recipients tend to develop a weaker immune response to vaccination. Anti-spike SARS-CoV-2 antibodies titers were measured 2-4 weeks post-vaccination completion in 131 KT patients without previous infection. Demographic, clinical, and laboratorial parameters were analyzed to identify which factors contributed to seroconversion. Factors that influenced seroconversion, that occurred in 76 patients (58%), were longer time post-transplant, immunosuppression without an antiproliferative drug and vaccination with mRNA vaccines. Patients who received mRNA vaccines had significantly higher rates of seroconversion compared with adenovirus vector vaccines (67% vs 33%, P < .001) and higher anti-spike IgG titers. These findings reinforce the need to discuss the vaccination strategy in this population, including a third dose with a mRNA vaccine.

Racism without racists and consequentialist life-maximizing approaches to triaging.

Consequentialist life-maximizing approaches to triaging prescribe that everyone ought to have an equal chance of living a typical lifespan, through the saving more life-years (or saving most lives) principle, which emphasizes the youngest-first principle and in some cases a lottery approach, often at the expense of the old and the sick. Although this approach has already been criticized by several bioethicists, this article provides a different kind of criticism to the life-cycle viewpoint, one that has not yet been explored at length; namely, we contend that the life-maximizing approach entails a form of racism without racists in its attitude towards Black people. More specifically, we contend that by neglecting the idea that current societies are not post-racial, it privileges White individuals and disadvantages Black people in the triaging process, curtails equal opportunities for Black people, reinforces white normativity, and neglects African culture. We end the article by pointing towards an Afro-communitarian relational triaging approach that does not face the same difficulties as consequentialist life-maximizing approaches do.

Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior.

Stressful life events are major environmental risk factors for anxiety disorders, although not all individuals exposed to stress develop clinical anxiety. The molecular mechanisms underlying the influence of environmental effects on anxiety are largely unknown. To identify biological pathways mediating stress-related anxiety and resilience to it, we used the chronic social defeat stress (CSDS) paradigm in male mice of two inbred strains, C57BL/6NCrl (B6) and DBA/2NCrl (D2), that differ in their susceptibility to stress. Using a multi-omics approach, we identified differential mRNA, miRNA and protein expression changes in the bed nucleus of the stria terminalis (BNST) and blood cells after chronic stress. Integrative gene set enrichment analysis revealed enrichment of mitochondrial-related genes in the BNST and blood of stressed mice. To translate these results to human anxiety, we investigated blood gene expression changes associated with exposure-induced panic attacks. Remarkably, we found reduced expression of mitochondrial-related genes in D2 stress-susceptible mice and in exposure-induced panic attacks in humans, but increased expression of these genes in B6 stress-susceptible mice. Moreover, stress-susceptible vs. stress-resilient B6 mice displayed more mitochondrial cross-sections in the post-synaptic compartment after CSDS. Our findings demonstrate mitochondrial-related alterations in gene expression as an evolutionarily conserved response in stress-related behaviors and validate the use of cross-species approaches in investigating the biological mechanisms underlying anxiety disorders.

Lower Limb Dynamic Activity Significantly Reduces Foot Skin Perfusion: Exploring Data with Different Optical Sensors in Age-Grouped Healthy Adults.

INTRODUCTION: The human lower limb is widely used as a model to study in vivo microcirculatory physiology and pathophysiology. It is a preferential target for critical comorbidities (overweight, diabetes, and peripheral vascular disease). Movement and activity are consistently regarded as beneficial, but the related adaptive physiology is still poorly understood. Our goal was to better identify the foot microcirculatory changes after a regular walking gait activity in healthy subjects of different ages. METHODS: Twelve healthy participants of both sexes, with normal BMI and Ankle-Brachial Index, were selected and grouped according to age - group I (21.0 ± 1 y.o.) and group II (55.8 ± 3 y.o.). The protocol involved 2 phases of 5-min duration each - phase 1, a static standing position, and phase 2, 5-min walking with a comfortable pace on a pre-established circuit. Perfusion changes were assessed in the dorsal region of both feet before (baseline, phase 1) and after (phase 2) the gait period by noninvasive optical technologies - laser Doppler flowmetry (LDF), photoplethysmography, and polarized spectroscopy (PSp). Comparative statistics were performed with a 95% confidence level. RESULTS: All instruments detected an asymmetric nonsignificant perfusion between right and left feet during rest in all participants with values in females consistently lower than men. Older participants exhibited lower baseline values than the younger group. Gait evoked a perfusion reduction in all participants relative to phase 1 detected with all technologies, with statistically significant changes recorded with LDF (group I, p = 0.033, and group II, p = 0.028) and PSp (group II, p = 0.041). Furthermore, LDF revealed that gait significantly reduced perfusion velocity in the older group (p = 0.003). Corresponding changes in the younger group were present but discrete. Recovery to baseline levels was also slower in the older group. DISCUSSION/CONCLUSIONS: Our results confirm that perfusion is age dependent and demonstrate the clinical relevance of simple dynamic activities such as gait. This reduction of the dorsal foot perfusion occurs in depth, being more pronounced with the movement intensity, suggesting a wide application potential in early diagnostics as for rehabilitation.

Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis.

BACKGROUND: Interstitial fibrosis, tubular atrophy (IFTA), and glomerulosclerosis are indicators of irrecoverable kidney injury. Modern machine learning (ML) tools have enabled robust, automated identification of image structures that can be comparable with analysis by human experts. ML algorithms were developed and tested for the ability to replicate the detection and quantification of IFTA and glomerulosclerosis that renal pathologists perform. METHODS: A renal pathologist annotated renal biopsy specimens from 116 whole-slide images (WSIs) for IFTA and glomerulosclerosis. A total of 79 WSIs were used for training different configurations of a convolutional neural network (CNN), and 17 and 20 WSIs were used as internal and external testing cases, respectively. The best model was compared against the input of four renal pathologists on 20 new testing slides. Further, for 87 testing biopsy specimens, IFTA and glomerulosclerosis measurements made by pathologists and the CNN were correlated to patient outcome using classic statistical tools. RESULTS: The best average performance across all image classes came from a DeepLab version 2 network trained at 40× magnification. IFTA and glomerulosclerosis percentages derived from this CNN achieved high levels of agreement with four renal pathologists. The pathologist- and CNN-based analyses of IFTA and glomerulosclerosis showed statistically significant and equivalent correlation with all patient-outcome variables. CONCLUSIONS: ML algorithms can be trained to replicate the IFTA and glomerulosclerosis assessment performed by renal pathologists. This suggests computational methods may be able to provide a standardized approach to evaluate the extent of chronic kidney injury in situations in which renal-pathologist time is restricted or unavailable.

A new species of Hoplias malabaricus species complex (Characiformes: Erythrinidae) from the Crepori River, Amazon basin, Brazil.

A new species belonging to the Hoplias malabaricus complex from the Amazon basin, Brazil, is described. The new species is characterized by 15-16 predorsal scales, 37-39 lateral-line scales, 5 scales from dorsal fin to lateral line, 38-39 vertebrae, iii-iv, 7-8 anal-fin rays, ii-iv, 12-15 caudal-fin rays, last vertical series of scales on the base of caudal-fin rays forming a straight line, 6-7 dark bands in anal fin and no distinctive dark bands or blotches on flanks. The new species is also distinguished from other congeners of the H. malabaricus species-group by means of landmark-based morphometrics and DNA Barcoding (Cytochrome c Oxidase I gene). An identification key to species of the H. malabaricus species complex is provided.

Food Ingredients Derived from Lemongrass Byproduct Hydrodistillation: Essential Oil, Hydrolate, and Decoction.

Essential oil (EO), hydrolate, and nondistilled aqueous phase (decoction) obtained from the hydrodistillation of lemongrass byproducts were studied in terms of their potential as food ingredients under a circular economy. The EO (0.21%, dry weight basis) was composed mainly of monoterpenoids (61%), the majority being citral (1.09 g/kg). The minimal inhibitory concentrations (MIC) of lemongrass EO against Escherichia coli, Salmonella enterica, and Staphylococcus aureus, were 617, 1550, and 250 µg/mL, respectively. This effect was dependent on the citral content. Particularly for Gram-negative bacteria, a synergism between citral and the remaining EO compounds enhanced the antimicrobial activity. The polymeric material obtained from the nondistilled aqueous phase was composed of phenolic compounds (25% gallic acid equivalents) and carbohydrates (22%), mainly glucose (66 mol%). This polymeric material showed high antioxidant activity due to bound phenolic compounds, allowing its application as a functional dietary fiber ingredient. Matcha green tea formulations were successfully mixed with lemongrass hydrolate containing 0.21% EO (dry weight basis) with 58% of monoterpenoids, being citral at 0.73 g/kg, minimizing matcha astringency with a citrus flavor and extending the product shelf life. This holistic approach to essential oils' hydrodistillation of Cymbopogon citratus byproducts allows for valorizing of the essential oil, hydrolate, and decoction for use as food ingredients.

Kinetics of torquetenovirus DNA load in a recent kidney transplant recipient with mild SARS-CoV-2 infection and a failed antibody response.

Kidney transplant (KT) recipients are at an increased risk for severe COVID-19 because of their immunosuppressed state. A 42-year-old KT patient was diagnosed with COVID-19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 became negative 48 days after detection. SARS-CoV-2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID-19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID-19.

Screening the dermatological potential of plectranthus species components: antioxidant and inhibitory capacities over elastase, collagenase and tyrosinase.

A series of Plectranthus spp. plant extracts (aqueous, acetonic, methanolic and ethyl acetic) obtained from eight different species, and previously isolated compounds (ranging from polyphenols, diterpenes and triterpenes), were assayed for in vitro inhibition of the skin-related enzymes tyrosinase, collagenase and elastase, and for studying their antioxidant properties. The ethyl acetic extracts of P. grandidentatus and P. ecklonii registered the highest antioxidant activity, whereas acetonic, methanolic and ethyl acetic extracts of P. ecklonii, P. grandidentatus, P. madagascariensis and P. saccatus concerning the enzymatic inhibition assays revealed high anti-tyrosinase and anti-collagenase activities. From the isolated compounds tested, abietane diterpenes and triterpenes were highly active against tyrosinase and elastase activity. Overall, the experimental results showed the powerful antioxidant and inhibitory action on skin-related enzymes tyrosinase, collagenase and elastase of Plectranthus spp. extracts and/or isolated compounds, supporting their further research as bioactive metabolites against skin sagging and hyperpigmentation in cosmetic and pharmaceutical formulations.

Injustice for the sake of public health: Freeing prisoners in Portugal during the COVID-19 pandemic.

This case study analysis looks at Portuguese policy during the COVID-19 pandemic whereby convicts were freed for the sake of public health. I defend this policy negatively by refuting the argument that suggested it involved various forms of injustice.

Model invariance of the Motor Competence Assessment (MCA) from early childhood to young adulthood.

The Motor Competence Assessment (MCA) is an innovative instrument to assess motor competence along the lifespan. The MCA model and normative values were recently established from the age of 3-to-23 years old. The purpose of this study was to validate MCA from early childhood to young adulthood.One thousand participants representing four age groups (3-6, 7-10, 11-16, 17-22 years) with 250 participants each, were assessed. Invariance of the MCA model along the age groups - configural, metric and structural - was tested using multigroup CFA.The MCA model showed to fit well all age groups. The multigroup unconstrained model showed a very good fit (NFI=0.99; TLI=0.99; CFI=0.99; RMSEA=0.03). A formal test for the invariance of loading coefficients returned a non-satisfactory goodness-of-fit adjustment and a significant difference with the unconstrained model (Δχ2 = 539.57; Δdf = 18; p= .00) . The structural invariance testing did not show formal invariance between factor correlations (Δχ2 = 73.04; Δdf = 9; p= .00) but the fit of the model was acceptable (above 0.96 and a RMSEA of 0.05), indicating that correlation values inter factors are stable.This study adds information for the validation of the MCA as a useful instrument for assessing motor competence throughout the life cycle.

Feasibility of using death certificates for studying place of death in Latin America.

OBJECTIVE: This paper assesses the availability and quality of death certificate data in Latin America and the feasibility of using these data to study place of death and associated factors. METHODS: In this comparative study, we collected examples of current official death certificates and digital data files containing information about all deaths that occurred during 1 year in 19 Latin American countries. Data were collected from June 2019 to May 2020. The records for place of death and associated variables were studied. The criteria for data quality were completeness, number of ill-defined causes of death and timeliness. RESULTS: All 19 countries provided copies of current official death certificates and 18 of these registered the place of death. Distinguishing among hospital or other health care institution, home and other was possible for all countries. Digital data files with death certificate data were available from 12 countries and 1 region. Three countries had data considered to be of high quality and seven had data considered to be of medium quality. Categories for place of death and most of the predetermined factors possibly associated with place of death were included in the data files. CONCLUSIONS: The quality of data sets was rated medium to high in 10 countries. Hence, death certificate data make it feasible to conduct an international comparative study on place of death and the associated factors in Latin America.