Lipidome remodeling in response to nutrient replenishment requires the tRNA modifier Deg1/Pus3 in yeast.

In the yeast Saccharomyces cerevisiae, the absence of the pseudouridine synthase Pus3/Deg1, which modifies tRNA positions 38 and 39, results in increased lipid droplet (LD) content and translational defects. In addition, starvation-like transcriptome alterations and induced protein aggregation were observed. In this study, we show that the deg1 mutant increases specific misreading errors. This could lead to altered expression of the main regulators of neutral lipid synthesis which are the acetyl-CoA carboxylase (Acc1), an enzyme that catalyzes a key step in fatty acid synthesis, and its regulator, the Snf1/AMPK kinase. We demonstrate that upregulation of the neutral lipid content of LD in the deg1 mutant is achieved by a mechanism operating in parallel to the known Snf1/AMPK kinase-dependent phosphoregulation of Acc1. While in wild-type cells removal of the regulatory phosphorylation site (Ser-1157) in Acc1 results in strong upregulation of triacylglycerol (TG), but not steryl esters (SE), the deg1 mutation more specifically upregulates SE levels. In order to elucidate if other lipid species are affected, we compared the lipidomes of wild type and deg1 mutants, revealing multiple altered lipid species. In particular, in the exponential phase of growth, the deg1 mutant shows a reduction in the pool of phospholipids, indicating a compromised capacity to mobilize acyl-CoA from storage lipids. We conclude that Deg1 plays a key role in the coordination of lipid storage and mobilization, which in turn influences lipid homeostasis. The lipidomic effects in the deg1 mutant may be indirect outcomes of the activation of various stress responses resulting from protein aggregation.

Immune status, well-being and gut microbiota in military supplemented with synbiotic ice cream and submitted to field training: a randomised clinical trial.

Strenuous physical activity, sleep deprivation and psychological stress are common features of military field training. The present study aimed to evaluate the effects of supplementation with a synbiotic ice cream on salivary IgA, gastrointestinal symptoms, well-being indicators and gut microbiota in young military participants undergoing field training. Sixty-five military completed the study: one group was supplemented for 30 d with synbiotic ice cream containing: 2·1 × 108 CFU/g for Lactobacillus acidophilus LA-5 and 2·7 × 109 CFU/g for Bifidobacterium animalis BB-12 and 2·3 g of inulin in the 60 g of ice cream at manufacture, and the other with a placebo ice cream. Volunteers were evaluated at pre-supplementation (baseline), post-supplementation and after a 5-d military training. Bifidobacterium and Lactobacillus genera were measured in stool samples and both showed a higher differential abundance post-supplementation and training. Salivary IgA and gastrointestinal symptoms decreased at post-training in both groups (P < 0·05; main effect of time); however, supplementation with synbiotic did not mitigate this effect. Tenseness and sleepiness were decreased in the synbiotic-treated group, but not in the placebo group at post-military training (P = 0·01 and 0·009, respectively; group × time effect). The other well-being indicators were not affected by the synbiotic supplementation. In conclusion, 30 d of synbiotic ice cream supplementation containing inulin, L. acidophilus LA-5 and B. animalis BB-12 favourably modulated gut microbiota and improved tenseness and sleepiness in healthy young military undergoing a 5-d field training. These improvements may be relevant to this population as they may influence the decision-making process in an environment of high physical and psychological stress.

Identification of caffeic acid and rutin by UHPLC MS/MS and antioxidant activity of Commelina erecta Lineu. in cell culture.

The Commelina erecta L. (C. erecta) also known as erva-de-santa-luzia is reported by local population to have medical properties against some pathological conditions. In this study, two extracts of C. erecta leaves (aqueous and ethanolic) were phytochemically analysed and evaluated for their in-vitro antioxidant activities by DPPH, TBARS, NO assays and cell viability assays. The ultra-high performance liquid chromatography followed by tandem mass spectrometry analysis showed the presence of rutin and caffeic acid in aqueous and ethanolic extract. The total polyphenols in aqueous and ethanolic extracts found were 142.7 ± 3.0 and 123.1 ± 5.8 µg/mL of GAE, respectively. The ethanolic extract (5 mg/mL) inhibits TBARS by 33.8%, and the aqueous extract (5 mg/mL) exhibited scavenger property against nitric oxide derivatives to an extent of 77.8%. In cell culture, both extracts improved cell survivability under H2O2 induced oxidative stress. Thus, C. erecta extract is a good candidate to become a phytotherapic medicine.

Association of testosterone with estrogen abolishes the beneficial effects of estrogen treatment by increasing ROS generation in aorta endothelial cells.

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testosterone associated with conjugated equine estrogen (CEE) on vascular function using a model of hypertensive postmenopausal female: ovariectomized spontaneously hypertensive rats. Female spontaneously hypertensive rats were divided into sham-operated, ovariectomized (OVX), and OVX treated for 15 days with either CEE alone (OVX+CEE) or associated with testosterone (OVX+CEE+T). Angiotensin II (ANG II)-induced contraction was markedly increased in aortic rings from OVX compared with sham-operated rats. CEE treatment restored ANG-II responses, a beneficial effect abrogated with CEE+T. CEE treatment also increased endothelium-dependent relaxation, which was impaired in OVX rats. This effect was lost by CEE+T. Treatment of aortas with losartan (ANG-II type-1 receptor antagonist) or apocynin (NADPH-oxidase inhibitor) restored the endothelium-dependent relaxation in OVX and CEE+T, establishing an interplay between ANG-II and endothelial dysfunction in OVX and CEE+T. The benefits by CEE were associated with downregulation of NADPH-oxidase subunits mRNA expression and decreased reactive oxygen species generation. The association of testosterone with CEE impairs the benefits of estrogen on OVX-associated endothelial dysfunction and reactive oxygen species generation in rat aorta by a mechanism that involves phosphorylation of the cytosolic NADPH-oxidase subunit p47(phox).

Wastewater surveillance for viral pathogens: A tool for public health.

A focus on water quality has intensified globally, considering its critical role in sustaining life and ecosystems. Wastewater, reflecting societal development, profoundly impacts public health. Wastewater-based epidemiology (WBE) has emerged as a surveillance tool for detecting outbreaks early, monitoring infectious disease trends, and providing real-time insights, particularly in vulnerable communities. WBE aids in tracking pathogens, including viruses, in sewage, offering a comprehensive understanding of community health and lifestyle habits. With the rise in global COVID-19 cases, WBE has gained prominence, aiding in monitoring SARS-CoV-2 levels worldwide. Despite advancements in water treatment, poorly treated wastewater discharge remains a threat, amplifying the spread of water-, sanitation-, and hygiene (WaSH)-related diseases. WBE, serving as complementary surveillance, is pivotal for monitoring community-level viral infections. However, there is untapped potential for WBE to expand its role in public health surveillance. This review emphasizes the importance of WBE in understanding the link between viral surveillance in wastewater and public health, highlighting the need for its further integration into public health management.

Giant intracranial aneurysms: morphology and clinical presentation.

The purpose of this study was to correlate the morphology of giant intracranial aneurysms (GIA) with their clinical presentation. Eighty patients with GIA, 14 males and 66 females, were studied. Univariate and multivariate analyses were made to test the associations between morphological and clinical features. The main locations of the unruptured GIA included the carotid cavernous segment, and for the ruptured GIA, the most frequent were the carotid supraclinoid and middle cerebral arteries. There was a significant association among communicating arteries (CA) of "bad" quality and presence of thrombus and calcification (TC). The risk of rupture is 8 times higher in patients with CA of "bad" quality and 11 times higher in patients without TC. GIA are more frequent in the cavernous segment. There is a high rupture risk in the middle cerebral artery. CA of "bad" quality are associated with TC. The rupture risk is significantly higher in patients without TC.

Plasma oxylipin profiling by high resolution mass spectrometry reveal signatures of inflammation and hypermetabolism in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons, systemic hypermetabolism, and inflammation. In this context, oxylipins have been investigated as signaling molecules linked to neurodegeneration, although their specific role in ALS remains unclear. Importantly, most methods focused on oxylipin analysis are based on low-resolution mass spectrometry, which usually confers high sensitivity, but not great accuracy for molecular characterization, as provided by high-resolution MS (HRMS). Here, we established an ultra-high performance liquid chromatography HRMS (LC-HRMS) method for simultaneous analysis of 126 oxylipins in plasma. Intra- and inter-day method validation showed high sensitivity (0.3-25 pg), accuracy and precision for more than 90% of quality controls. This method was applied in plasma of ALS rats overexpressing the mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A) at asymptomatic (ALS 70 days old) and symptomatic stages (ALS 120 days old), and their respective age-matched wild type controls. From the 56 oxylipins identified in plasma, 17 species were significantly altered. Remarkably, most of oxylipins linked to inflammation and oxidative stress derived from arachidonic acid (AA), like prostaglandins and mono-hydroxides, were increased in ALS 120 d rats. In addition, ketones derived from AA and linoleic acid (LA) were increased in both WT 120 d and ALS 120 d groups, supporting that age also modulates oxylipin metabolism in plasma. Interestingly, the LA-derived diols involved in fatty acid uptake and ß-oxidation, 9(10)-DiHOME and 12(13)-DiHOME, were decreased in ALS 120 d rats and showed significant synergic effects between age and disease factors. In summary, we validated a high-throughput LC-HRMS method for oxylipin analysis and provided a comprehensive overview of plasma oxylipins involved in ALS disease progression. Noteworthy, the oxylipins altered in plasma have potential to be investigated as biomarkers for inflammation and hypermetabolism in ALS.

Long-term monitoring of COVID-19 prevalence in raw and treated wastewater in Salvador, the largest capital of the Brazilian Northeast.

Wastewater-based epidemiology (WBE) becomes an interesting epidemiological approach to monitoring the prevalence of SARS-CoV-2 broadly and non-invasively. Herein, we employ for the first time WBE, associated or not with the PEG 8000 precipitation method, for the detection of SARS-CoV-2 in samples of raw or treated wastewater from 22 municipal wastewater treatment stations (WWTPs) located in Salvador, the fourth most populous city in Brazil. Our results demonstrate the success of the application of WBE for detecting SARS-CoV-2 in both types of evaluated samples, regardless of the usage of PEG 8000 concentration procedure. Further, an increase in SARS-CoV-2 positivity rate was observed in samples collected in months that presented the highest number of confirmed COVID-19 cases (May/2021, June/2021 and January/2022). While PEG 8000 concentration step was found to significantly increase the positivity rate in treated wastewater samples (p < 0.005), a strong positive correlation (r: 0.84; p < 0.002) between non-concentrated raw wastewater samples with the number of new cases of COVID-19 (April/2021-February/2022) was observed. In general, the present results reinforce the efficiency of WBE approach to monitoring the presence of SARS-CoV-2 in either low- or high-capacity WWTPs. The successful usage of WBE even in raw wastewater samples makes it an interesting low-cost tool for epidemiological surveillance.

Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats.

Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardio-vascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study, we hypothesize that inhibition of TLR4 decreases BP (blood pressure) and improves vascular contractility in resistance arteries from SHR (spontaneously hypertensive rats). TLR4 protein expression in mesenteric resistance arteries was higher in 15-week-old SHR than in age-matched Wistar controls or in 5-week-old SHR. To decrease the activation of TLR4, 15-week-old SHR and Wistar rats were treated with anti-TLR4 (anti-TLR4 antibody) or non-specific IgG control antibody for 15 days (1 µg per day, intraperitoneal). Treatment with anti-TLR4 decreased MAP (mean arterial pressure) as well as TLR4 protein expression in mesenteric resistance arteries and IL-6 (interleukin 6) serum levels from SHR when compared with SHR treated with IgG. No changes in these parameters were found in treated Wistar control rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to NA (noradrenaline) compared with IgG-treated SHR. Inhibition of COX (cyclo-oxygenase)-1 and COX-2, enzymes related to inflammatory pathways, decreased NA responses only in mesenteric resistance arteries of SHR treated with IgG. COX-2 expression and TXA2 (thromboxane A2) release were decreased in SHR treated with anti-TLR4 compared with IgG-treated SHR. Our results suggest that TLR4 activation contributes to increased BP, low-grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.

Bioactive compounds and hepatoprotective effect of Hancornia speciosa gomes fruit juice on acetaminophen-induced hepatotoxicity in vivo.

Hancornia speciosa Gomes (HS) is a Brazilian fruit tree used in inflammatory disorders by folk medicine. Here we sought to investigate the antioxidant and hepatoprotective properties of HS fruit juice in acetaminophen-induced hepatoxicity model in rats, as well as to perform a comprehensive chemical characterization of phenolics and metals by mass spectrometry. HS showed hepatoprotective and antioxidant activity by decreasing MDA and liver injury markers at healthy control levels. In addition, liver histopathological analysis revealed that HS decreases hepatocellular degeneration. Chemical characterization revealed 16 different phenolics, being chlorogenic acid (150 ± 5 µg/g) and rutin (120 ± 8 µg/g) the major phenolics in HS. Among the 14 micronutrients we identified, zinc and boron were the most abundant metals detected in HS. In line with previous studies involving liver diseases, our data supports evidence that such phenolics and metals present in HS may prevent liver injury induced by acetaminophen.

Loss of life estimation and risk level classification due to a dam break.

This report estimated the loss of life and the variation of risk level to people and properties from the city of São José do Jacuípe, at Bahia State, in Brazil, through a simulation of the dam break near the city. The simulations employ the HEC-RAS program with the HEC-GeoRAS plugin, both made available by the U.S. Army Corps of Engineers. The program is a hydrological model for the hydric flow propagation arising from the complete resolution of the Saint-Venant equation, while the plugin was used for vector editing by creating a geomorphological model from the river basin. The results from the research demonstrated that the city is exposed to a risk that is time dependent. In addition, the lack of a warning system about a possible break could cause the death of almost all residents. Otherwise, with a warning system operating, the estimation of destruction would be dramatically reduced.

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression.

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.

Transition of blind women to motherhood from the perspective of Transitions Theory.

OBJECTIVE: to analyze the transition of blind women to motherhood from the perspective of Transitions Theory. METHOD: a qualitative, descriptive study, which had as participants 11 blind women. An open interview was conducted using the narrative method. Analysis occurred in the light of Transitions Theory, with approval from the Research Ethics Committee with Human Beings. RESULTS: the age group was 32 to 63 years, mostly Catholic, with social security benefits. Transition to motherhood mainly evidenced the experience when becoming a mother and feelings related to this new phase of life. FINAL CONSIDERATIONS: the women in the study adapted themselves to the maternal role, even with difficulties, developed healthy relationships with their children, overcame their disability and nurtured dreams and desires. They were aware of their role, achieving with mastery a healthy transition. It was evidenced scarcity of nursing therapies.

Malformation and death X Alcoholism: perspective of Nursing the Theory of Transitions for alcoholic pregnant women.

OBJECTIVE: To analyze the knowledge of women who are being treated in Psychosocial Care Centers for Alcohol and Drugs about the harm caused by alcohol consumption during pregnancy, especially regarding fetal malformation. METHOD: Qualitative, descriptive and exploratory study using the Life Narrative approach. Data was collected between February and May 2016, in the city of Rio de Janeiro, with an open interview with the guiding question: "Tell me about your life in relation to alcohol consumption during pregnancy and the guidance received in prenatal care". RESULTS: The narratives revealed lack of information and fear of malformation (physical) and fetal death due to alcohol consumption during pregnancy. DISCUSSION: Malformation or fetal death may trigger a transitional process in women. FINAL CONSIDERATIONS: Women have incipient knowledge about the effects of alcohol on the fetus. They consider that alcohol can only cause physical defects in the children.

Research in nursing and modification of the knowledge tree in CNPq: contribution to science.

OBJECTIVE: to identify funding demands in the light of CNPq's knowledge subareas, as well as data on researchers and research groups, their distribution in the regions and their approximation with health research priorities of the Ministry of Health and the new knowledge tree framework of the area. METHOD: a descriptive study developed with data from 2009 to 2014 about researchers, funding and research areas provided by the Diretoria de Ciências Agrárias Biológicas e Saúde (Department of Agriculture, Biology and Health Sciences). RESULTS: there is a concentration of researchers and research groups in the Southeast region. The research priorities in the health field most frequently addressed were: Noncommunicable Diseases, Child and Adolescent Health, Women's Health and Communicable diseases. The grants could be classified in the current framework of knowledge areas. FINAL CONSIDERATIONS: this analysis enabled visualizing subarea demands and relevance of changing the nomenclature of the classification of knowledge framework in order to represent the scientific production generated in the nursing area.

Transition to motherhood and mothering for women in wheelchairs: a nursing perspective.

OBJECTIVE: To discuss the process of transition to motherhood and mothering of women who are wheelchair users, from the perspective of Afaf Ibrahim Meleis. METHOD: Qualitative, descriptive, exploratory study conducted with six women in the state of Rio de Janeiro. The Life Narrative method was used, with thematic analysis in the light of Transitions Theory. RESULTS: Developmental and situational transitions occurred and were influenced by personal, community and social factor. Moved mainly by ignorance and prejudice of family members and of the social network, these factors were not barriers for motherhood and mothering. FINAL CONSIDERATIONS: The reproductive rights of women with disabilities must be respected and, for this, inclusive policies focused on women with disabilities should be adopted.

Does antennal sensilla pattern of different populations of Triatoma maculata (Hemiptera: Reduviidae) reveal phenotypic variability?

BACKGROUND: In Brazil, Triatoma maculata is only found in the State of Roraima and is a vector of Trypanosoma cruzi, the etiological agent of Chagas disease. It occurs in wild, peridomestic and domestic habitats, with an urban infestation in Boa Vista, the capital of this Brazilian state. The aim of this study was to assess the morphological variability of the T. maculata antennal phenotype in three populations of Roraima State, using the antennal sensilla pattern analyzed under optical microscopy. METHODS: The number and distribution of four antennal sensilla types (bristles, thin and thick walled trichoidea, and basiconic) of three Brazilian populations of T. maculata from Roraima State were compared. Univariate and multivariate analyses were performed. RESULTS: The antenna of T. maculata presented the four types of sensilla. According to the density and distribution of the antennal sensilla characteristics, the multivariate analyses showed that the laboratory population is morphologically structured. Urban specimens showed a pronounced phenotypic variability. The main differences were observed in the pedicel segment, and between males and females. CONCLUSIONS: We determined the antennal phenotype in three Roraima populations of T. maculata. These results support the idea that the patterns of antennal sensilla are sensitive markers for distinct populations in the Triatominae. The infestations of T. maculata in different habitats reinforces the ability of this vector to become adapted to a variety of environments, which, could have eco-epidemiological implications for the T. cruzi transmission that are still not well understood.

Electronic prescription: frequency and severity of medication errors.

OBJECTIVE: To assess the frequency and severity of prescriptions errors with potentially dangerous drugs (heparin and potassium chloride for injection concentrate) before and after the introduction of a computerized provider order entry (CPOE) system. METHODS: This is a retrospective study that compared errors in manual/pre-typed prescriptions in 2007 (Stage 1) with CPOE prescriptions in 2014 (Stage 2) (Total = 1,028 prescriptions), in two high-complexity hospitals of Belo Horizonte, Brasil. RESULTS: An increase of 25% in the frequency of errors in Hospital 1 was observed after the intervention (p<0.001). In contrast, a decreased error frequency of 85% was observed in Hospital 2 (p<0.001). Regarding potassium chloride, the error rate remained unchanged in Hospital 1 (p>0.05). In Hospital 2, a significant decrease was recorded in Stage 2 (p<0.001). A reduced error severity with heparin (p<0.001) was noted, while potassium chloride-related prescription severity remain unchanged (p> 0.05). CONCLUSIONS: The frequency and severity of medication errors after the introduction of CPOE was affected differently in the two hospitals, which shows a need for thorough observation when the prescription system is modified. Control of new potential errors introduced and their causes for the adoption of measures to prevent these events must be in place during and after the implementation of this technology.

Interplay between food and gut microbiota in health and disease.

Numerous microorganisms colonize the human gastrointestinal tract playing pivotal roles in relation to digestion and absorption of dietary components. They biotransform food components and produce metabolites, which in combination with food components shape and modulate the host immune system and metabolic responses. Reciprocally, the diet modulates the composition and functional capacity of the gut microbiota, which subsequently influence host biochemical processes establishing a system of mutual interaction and inter-dependency. Macronutrients, fibers, as well as polyphenols and prebiotics are strong drivers shaping the composition of the gut microbiota. Especially, short-chain fatty acids produced from ingested fibers and tryptophan metabolites are key in modulating host immune responses. Since reciprocal interactions between diet, host, and microbiota are personal, understanding this complex network of interactions calls for novel use of large datasets and the implementation of machine learning algorithms and artificial intelligence. In this review, we aim to provide a base for future investigations of how interactions between food components and gut microbiota may influence or even determine human health and disease.

Enalapril treatment corrects the reduced response to bradykinin in diabetes increasing the B2 protein expression.

Considering the growing importance of the interaction between components of kallikrein-kinin and renin-angiotensin systems in physiological and pathological processes, particularly in diabetes mellitus, the aim of the present study was to investigate the effect of enalapril on the reduced response of bradykinin and on the interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems, in an insulin-resistance model of diabetes. For the above purpose, the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. In n-STZ diabetic rats, enalapril treatment restored the reduced response to BK but not the potentiation of BK by Ang-(1-7) present in non-diabetic rats. The restorative effect of enalapril was observed at a dose that did not correct the altered parameters induced by diabetes such as hyperglycemia, glicosuria, insulin resistance but did reduce the high blood pressure levels of n-SZT diabetic rats. There was no difference in mRNA and protein expressions of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Enalapril treatment increased the B2 kinin receptor expression. From our data, we conclude that in diabetes enalapril corrects the impaired BK response probably by increasing the expression of B2 receptors. The lack of potentiation of BK by Ang-(1-7) is not corrected by this agent.