Antiretroviral adherence among people living with HIV during the postpartum period: a retrospective cohort study at a PMTCT reference center in Rio de Janeiro before and during the COVID-19 pandemic.

Despite success in achieving viral suppression during pregnancy in people living with HIV (PLWH), postpartum adherence remains a challenge. We aimed to describe rates of adherence at a Prevention of Mother-to-Child HIV Transmission (PMTCT) Center before and during the COVID-19 pandemic. This study was conducted from a cohort of PLWH who received prenatal care and were virally suppressed near delivery. We tracked combined antiretroviral therapy (cART) pickups for 12 months and HIV viral load (VL) from 2 to 12 months after delivery. We defined flexible adherence as a monthly pickup of cART and strict adherence as also having VL < 200 copies/mL and at least one maternal HIV VL between two and twelve months postpartum. Pre-pandemic was defined as delivery from March 2017-February 2019 and pandemic as March 2020-February 2022. During the study, 1119 PLWH were followed, and 965 (86%) were suppressed near delivery. There were 511 pre-pandemic and 290 pandemic participants. Adherence rates were 66/511 (13%) and 38/290 (13%), respectively. During the pandemic, more participants conceived using cART and were undetectable at the start of prenatal care; nevertheless, postpartum adherence was no better than pre-pandemic underscoring the need to improve strategies for adherence specific to this subset of PLWH in the postpartum period.

Exercise training and diet-induced weight loss increase markers of hepatic bile acid (BA) synthesis and reduce serum total BA concentrations in obese women.

Regular exercise has profound metabolic influence on the liver, but effects on bile acid (BA) metabolism are less well known. BAs are synthesized exclusively in the liver from cholesterol via the rate-limiting enzyme cholesterol 7 alpha-hydroxylase (CYP7A1). BAs contribute to the solubilization and absorption of lipids and serve as important signaling molecules, capable of systemic endocrine function. Circulating BAs increase with obesity and insulin resistance, but effects following exercise and diet-induced weight loss are unknown. To test if improvements in fitness and weight loss as a result of exercise training enhance BA metabolism, we measured serum concentrations of total BAs (conjugated and unconjugated primary and secondary BAs) in sedentary, obese, insulin-resistant women (N = 11) before (PRE) and after (POST) a ∼14-wk exercise and diet-induced weight loss intervention. BAs were measured in serum collected after an overnight fast and during an oral glucose tolerance test (OGTT). Serum fibroblast growth factor 19 (FGF19; a regulator of BA synthesis) and 7-alpha-hydroxy-cholesten-3-one (C4, a marker of CYP7A1 enzymatic activity) also were measured. Using linear mixed-model analyses and the change in V̇O2peak (mL/min/kg) as a covariate, we observed that exercise and weight loss intervention decreased total fasting serum BA by ∼30% (P = 0.001) and increased fasting serum C4 concentrations by 55% (P = 0.004). C4 was significantly correlated with serum total BAs only in the POST condition, whereas serum FGF19 was unchanged. These data indicate that a fitness and weight loss intervention modifies BA metabolism in obese women and suggest that improved metabolic health associates with higher postabsorptive (fasting) BA synthesis. Furthermore, pre- vs. postintervention patterns of serum C4 following an OGTT support the hypothesis that responsiveness of BA synthesis to postprandial inhibition is improved after exercise and weight loss.NEW & NOTEWORTHY Exercise and weight loss in previously sedentary, insulin-resistant women facilitates a significant improvement in insulin sensitivity and fitness that may be linked to changes in bile acid metabolism. Diet-induced weight loss plus exercise-induced increases in fitness promote greater postabsorptive bile acid synthesis while also sensitizing the bile acid metabolic system to feedback inhibition during a glucose challenge when glucose and insulin are elevated.

Weight Loss, but Not Dairy Composition of Diet, Moderately Affects Satiety and Postprandial Gut Hormone Patterns in Adults.

BACKGROUND: Inclusion of dairy in diet patterns has been shown to have mixed effects on weight loss. A prevailing hypothesis is that dairy improves weight loss by influencing endocrine systems associated with satiety and food intake regulation. OBJECTIVES: The objective of the current study was to evaluate the effect of weight loss with or without adequate dietary dairy on subjective and objective appetitive measures. METHODS: Men and women who were habitual low dairy consumers (n = 65, 20-50 y) participated in a 12-wk randomized controlled feeding weight loss trial. During the 12-wk intervention, a low-dairy (<1 serving dairy/d) was compared with an adequate-dairy (3-4 servings dairy/d) diet, both with a 500-kcal deficit/d. Test days, before and at the end of the intervention, began with 2 fasting blood draws and visual analog scale (VAS) measures, followed by a standard breakfast (25% of prescribed restricted calories), 5 postbreakfast blood draws and VASs, a standard lunch (40% of restricted energy amount), and 12 postlunch blood draws and VASs. Blood samples were used for satiety hormone measurements. On a separate day when matching standard meals were consumed, an ad libitum buffet meal was provided as dinner, at a self-selected time. Meal duration and intermeal interval were recorded. RESULTS: Weight loss (-6.1 kg), irrespective of dairy, resulted in reduced fasting insulin (-20%) and leptin (-25%), and increased fasting acylated ghrelin (+25%) and VAS desire to eat (+18%) (P < 0.05). There were no effects of dairy on objective or subjective satiety measures. Weight loss marginally reduced the intermeal interval (289 min compared with 276 min, P = 0.059) between lunch and the ad libitum buffet. CONCLUSIONS: These results do not support the hypothesis that inclusion of dairy in long-term dietary patterns influences appetite during weight loss. Weight loss per se has a modest impact on select systems that regulate hunger and satiety.This trial was registered at clinicaltrials.gov as NCT00858312.

Different loci control resistance to different isolates of the same race of Colletotrichum lindemuthianum in common bean.

KEY MESSAGE: Linkage and genome-wide association analyses using high-throughput SNP genotyping revealed different loci controlling resistance to different isolates of race 65 of Colletotrichum lindemuthianum in common bean. Development of varieties with durable resistance to anthracnose is a major challenge in common bean breeding programs because of the extensive virulence diversity of Colletotrichum lindemuthianum fungus. We used linkage and genome-wide association analyses to tap the genomic regions associated with resistance to different isolates of race 65. Linkage mapping was done using an F2 population derived from the cross between the Mesoamerican common beans BRS Estilo x Ouro Vermelho, inoculated with two different isolates of race 65. Association genetics relied on a diversity common bean panel containing 189 common bean accessions inoculated with five different isolates of race 65 as an attempt to validate the linkage analysis findings and, eventually, identify other genomic regions associated with resistance to race 65. The F2 population and diversity panel were genotyped with the BARCBean6K_3 Illumina BeadChip containing 5398 SNP markers. Both linkage and genome-wide association analyses identified different loci controlling resistance to different isolates of race 65 on linkage group Pv04. Genome-wide association analysis also detected loci on Pv05, Pv10 and Pv11 associated with resistance to race 65. These findings indicate that resistance to race 65 can be overcome by the virulence diversity among different isolates of the same race and could lead to the loss of resistance after cultivar release. We identified 25 resistant common bean cultivars to all five isolates of race 65 in the diversity panel. The accessions should be useful to develop cultivars combining different resistance genes that favor durable resistance to anthracnose in common bean.

Chikungunya Virus Infection Outcome: A Systematic Review of Host Genetics.

Background: Chikungunya virus (CHIKV) is a global concern, inducing chikungunya fever and trigging an arthritogenic chronic phase beyond some severe forms. Outcomes of CHIKV infections in humans are dependent on genetic variations. Here, a systematic review was performed to show evidence of genetic variations on infection outcomes of patients. Methods: Searches were performed in Scopus, SciELO, MEDLINE/PubMed, Web of Science, OneFile (GALE), Periódicos CAPES and ScienceDirect Journals databases. The PICOS approach was used to assess the eligibility of records. A meta-analysis was also conducted to show an association between described alleles/genes and CHIKV infection outcome. Results: Reviews of genetic variants were conducted on genes: CD 209, OAS1, OAS2, OAS3, MIF, TLR-3, TLR-7, TLR-8, MYD-88, KIR, HLA-B; HLA-C; DRB1 and DQB1. Studies were performed on Gabon, Singapore, and India, including Indians, Malay, Gabonese and Chinese ethnicities and published between 2009-2017. The meta-analysis was performed with DRB1 *01; *03; *04; *07; *10; *11; *13; *14 and *15 and DQB1 *02; *03; *05 and *06 alleles with Indian population sample. Sampling power was >80% and a significant positive association between DRB1*14 and CHIKV infection was found (OR = 1.67, 95% CI = 1.04-2.67; p = .03). Conclusion: Majority of the studies were conducted in India. Meta-analysis suggests that DRB1*14 is related to the susceptibility of symptomatic CHIKV infection in Indian population. The literature about CHIKV infection and genetic variations is scarce. The precise role of genetic variation in CHIKV is not clear yet. Further studies are necessary to provide more concrete evidences.

Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis.

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools.Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies.Results: A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA -308 G > A and IL-10 - 1082A>G) and ZNF263 (TNFA -238 G > A) transcription factors binding.Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.

Role of neuroendocrine modulation and biochemistry in the sepsis in Piaractus mesopotamicus.

Sepsis is a systemic process with multifactorial pathophysiology that affects most animal species. It is responsible for high rates of morbidity and mortality. This work aimed to study the biochemical and neuroendocrine changes of the sepsis process in Piaractus mesopotamicus after Aeromonas hydrophila inoculation analyzing changes in blood leukocyte and differences in neuroendocrine-biochemical modulation using RNA-seq. Fish showed hypercortisolemia, inhibition of glucose absorption, followed by hypocortisolemia and then hyperglycemia. Thyroid hormones (T3 and T4) showed immediate decrease in serum and T4 increased 6 h post-inoculation (HPI). Sepsis-induced hormonal alterations triggered changes in the metabolic pathways increasing protein and lipid catabolism, use of transient anaerobic glycolysis and liver injury. A reference transcriptome was constructed based on blood leukocytes from P. mesopotamicus. The assembly resulted in total 266,272 contigs with a N50 of 2786 bp. There was a reorganization of plasma membrane of leukocytes at the beginning of the septic process with increased expression of neuroendocrine receptors and with continuous flow of neurotransmitters, hormones and solutes with compensatory regulation at 6 HPI. Three and nine HPI seemed to be critical, the expression of a number of transcription factors was increased, including the modulatory DEGs related to glucocorticoid and thyroid hormones induced and suppressed (FDR < 0.05). Neuroendocrine modulation can regulate leukocytes and biochemical parameters of peripheral blood, being important sources for the study of the pathophysiology of sepsis. These finding highlights the importance of further studies focusing on biochemical-neuroendocrine changes in blood leukocytes and systemic sepsis.

Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention.

Insulin resistance has wide-ranging effects on metabolism, but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ∼45% of V̇o2peak, ∼63 W) and recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ∼14-wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise, regardless of pre- versus postintervention status, highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of nonoxidative fates of glucose [e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside (possible glycerolipid synthesis metabolite)], and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites ("non-self" molecules, from microbes or foods), including benzoic acid-salicylic acid-salicylaldehyde, hexadecanol-octadecanol-dodecanol, and chlorogenic acid. In addition, many nonannotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results and previously reported plasma acylcarnitine profiles support the principle that most metabolic changes during submaximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.

Modulation of hepatic copper-ATPase activity by insulin and glucagon involves protein kinase A (PKA) signaling pathway.

Different studies have revealed copper imbalance in individuals suffering from diabetes and obesity, suggesting that regulation of glucose and/or fat metabolism could modulate cellular copper homeostasis. To test this hypothesis we investigated whether the key hormones of energy metabolism, insulin and glucagon, regulate the functional properties of the major hepatic copper-transporter, ATP7B (i.e., copper-dependent ATPase activity). We demonstrated that insulin reverses the effect of copper and stimulates retrograde trafficking of ATP7B from the canalicular membranes, consistent with the enhanced ability of ATP7B to sequester copper away from the cytosol. Physiological concentrations of insulin increase endogenous ATP7B activity in cultured hepatic cells and in tissues by 40%, whereas glucagon inhibits this activity by 70%. These effects were cancelled out when insulin and glucagon were combined. We also demonstrated that the opposite effects of the hormones on ATP7B activity involve receptor-mediated signaling pathways and membrane-bound kinases (PKA and PKB/Akt), which are reciprocally regulated by insulin and glucagon. Inhibiting insulin signaling at the level of its Tyr-kinase receptor, PI3K or PKB/Akt restored the basal activity of ATP7B. Insulin reduced endogenous PKA activity, whereas glucagon promoted PKA stimulation by approximately 100%. These findings demonstrate that the physiological modulation of ATP7B activity is linked to energy metabolism via insulin and glucagon, and could help to understand the mechanisms involved in the disruption of copper homeostasis in diabetic and obese patients.

Dissecting copper homeostasis in diabetes mellitus.

Diabetes Mellitus (DM) is characterized by elevated blood glucose levels (hyperglycemia). It can occur due to impaired secretion or action of the hormone insulin, which is produced by pancreatic beta-cells to promote the entry of glucose into the cells. It is known that hyperglycemia has an important role in the production of reactive oxygen species in all types of DM and that an imbalance of transition metal as Cu and Fe plays a pivotal role in stimulating the oxidative stress. Different levels of some transition metals, as Cu, Fe, Mn, and Zn has been reported comparing diabetic animal models with the control group. An increased Cu status is also described in diabetic patients. Homeostasis of Cu depends on distinct proteins, where Cu(I)-ATPases are important transmembrane proteins for acquisition, active transport, distribution and elimination of Cu ions. In this review we first provide an overview of the literature about the relationship between diabetes and copper, the modulation of Cu(I)-ATPases activity and protein expression in DM, to next discuss the alternative treatments for diabetes using Cu chelation. © 2016 IUBMB Life, 69(4):255-262, 2017.

Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons.

NEW FINDINGS: What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover. With insulin resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives [markers of incomplete long-chain fatty acid oxidation (FAO)]. We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 week training and weight-loss intervention in obese, sedentary, insulin-resistant women. Contrary to this hypothesis, overnight-fasted and exercise-induced plasma C4-C14 acylcarnitines did not differ between pre- and postintervention phases. These metabolites all increased robustly with exercise (∼45% of pre-intervention peak oxygen consumption) and decreased during a 20 min cool-down. This supports the idea that, regardless of insulin sensitivity and fitness, intramitochondrial muscle ß-oxidation and attendant incomplete FAO are closely tethered to absolute ATP turnover rate. Acute exercise also led to branched-chain amino acid acylcarnitine derivative patterns suggestive of rapid and transient diminution of branched-chain amino acid flux through the mitochondrial branched-chain ketoacid dehydrogenase complex. We confirmed our prior novel observation that a weight-loss/fitness intervention alters plasma xenometabolites [i.e. cis-3,4-methylene-heptanoylcarnitine and γ-butyrobetaine (a co-metabolite possibly derived in part from gut bacteria)], suggesting that host metabolic health regulated gut microbe metabolism. Finally, we considered whether acylcarnitine metabolites signal to muscle-innervating afferents; palmitoylcarnitine at concentrations as low as 1-10 µm activated a subset (∼2.5-5%) of these neurons ex vivo. This supports the hypothesis that in addition to tracking exercise-associated shifts in fuel metabolism, muscle acylcarnitines act as signals of exertion to short-loop somatosensory-motor circuits or to the brain.

Volatile Organic Compounds in the Atmosphere of the Botanical Garden of the City of Rio de Janeiro: A Preliminary Study.

Volatile organic compounds (VOCs) play a central role in atmospheric chemistry. In this work, VOCs in the Botanical Garden of Rio de Janeiro were determined using the TO-15 Method. The park occupies 1,370,000 m2 in the southern area of the city and is next to the Tijuca Forest, which is considered the largest secondary urban forest in the world. The total VOC concentrations ranged from 43.52 to 168.75 µg m-3, depending on the sampling site and dates. In terms of concentration isoprene represented 4 %-14 % of the total VOC masses. The results suggested that the differences in biomass, distance from the street and activities within the park affected the concentrations of VOCs. The ratios of isoprene/aromatic compounds were higher than those determined in other areas of the city, confirming that the atmosphere of this green area has the contribution of other sources. Kinetic and mechanistic reactivities were also evaluated.

Reduced systemic microvascular density and reactivity in individuals with early onset coronary artery disease.

OBJECTIVE: This study sought to test whether patients with early-onset coronary artery disease (EOCAD, n=30) showed systemic microvascular rarefaction and endothelial dysfunction in comparison to age- and sex-matched healthy controls (CTL, n=30), as evaluated by skin video-capillaroscopy. METHODS: Functional capillary density (FCD) was defined as the number of spontaneously perfused capillaries per square millimeter of skin area and assessed by high-resolution intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using post-occlusive reactive hyperemia (PORH) after arm ischemia for 3min. RESULTS: The mean capillary density at rest was significantly reduced in patients with EOCAD compared to controls (CTL 95±20 and EOCAD 80±18capillaries/mm(2), P=0.0040). During PORH, capillary density was also markedly reduced in EOCAD patients (CTL 96±18 and EOCAD 71±20capillaries/mm(2), P<0.0001). Moreover, the capillary density in EOCAD patients was significantly reduced during PORH (EOCAD at rest 80±19 and EOCAD during PORH 71±20capillaries/mm(2), P=0.0073). CONCLUSIONS: Patients with EOCAD presented systemic capillary rarefaction and impaired microvascular endothelial function. Thus, the early detection of these microvascular alterations in young adults at an increased risk of coronary artery disease could be useful as a surrogate marker of subclinical atherosclerosis.

A Sensitive and Selective Label-Free Electrochemical DNA Biosensor for the Detection of Specific Dengue Virus Serotype 3 Sequences.

Dengue fever is the most prevalent vector-borne disease in the world, with nearly 100 million people infected every year. Early diagnosis and identification of the pathogen are crucial steps for the treatment and for prevention of the disease, mainly in areas where the co-circulation of different serotypes is common, increasing the outcome of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Due to the lack of fast and inexpensive methods available for the identification of dengue serotypes, herein we report the development of an electrochemical DNA biosensor for the detection of sequences of dengue virus serotype 3 (DENV-3). DENV-3 probe was designed using bioinformatics software and differential pulse voltammetry (DPV) was used for electrochemical analysis. The results showed that a 22-m sequence was the best DNA probe for the identification of DENV-3. The optimum concentration of the DNA probe immobilized onto the electrode surface is 500 nM and a low detection limit of the system (3.09 nM). Moreover, this system allows selective detection of DENV-3 sequences in buffer and human serum solutions. Therefore, the application of DNA biosensors for diagnostics at the molecular level may contribute to future advances in the implementation of specific, effective and rapid detection methods for the diagnosis dengue viruses.

Association between Carotid Intima-media Thickness and Early-onset Coronary Artery Disease: Does the site of Sonographic Evaluation Matter?

BACKGROUND: Intima-media thickness (IMT) is frequently used for risk stratification (RS) due to the association with coronary artery disease (CAD). Nonetheless, the best carotid site to scan is uncertain, especially in the young. The aim of this study was to evaluate the diagnostic performance of IMT measurements performed at different carotid sites. METHODS: Eighty-nine subjects ≤45 years were studied (55 with known CAD and 34 controls). IMT measurements were performed at the common carotid (CC), bulb and internal branch (IB) of both carotid arteries, (2112 measures). The diagnostic performance of IMT measurements performed at different sites, regarding the presence of CAD, was evaluated with ROC curves. RESULTS: Carotid plaques were found in 20.0% of the patients and 6.0% of the controls. The diagnostic performance of carotid IMT measures obtained at the CC, bulb or IB was not significantly different, with the CC and IB being slightly better (AUC ROC =0.82 and 0.80 respectively). CONCLUSIONS: IMT measures obtained at different carotid sites are associated with CAD in young (≤45 years) individuals. The diagnostic performance of IMT measured at the CC and IB is the more accurate measure, and this may be the most adequate for the measurement of IMT in this population.

Identification of Iodotyrosines as Novel Substrates for the Thyroid Hormone Transporter MCT8.

Background: Monocarboxylate transporter 8 (MCT8) is the most specific thyroid hormone transporter identified to date, deficiency of which has been associated with severe intellectual and motor disability and abnormal serum thyroid function tests. However, it is presently unknown if MCT8, similar to other thyroid hormone transporters, also accepts additional substrates, and if disruption of their transport may contribute to the observed phenotype. Methods: In this study, we aimed to identify such substrates by applying liquid chromatography-mass spectrometry-based metabolome analysis in lysates of control and MCT8-overexpressing Xenopus oocytes. A subset of identified candidate substrates were validated by direct transport studies in transiently transfected COS-1 cells and human fibroblasts, which endogenously express MCT8. Moreover, transport characteristics were determined, including transport saturation and cis-inhibition potency of thyroid hormone transport. Results: Metabolome analysis identified 21 m/z ratios, corresponding to 87 candidate metabolites, with a 2.0-times differential abundance in MCT8-injected oocytes compared with controls. These metabolites included 3,5-diiodotyrosine (DIT) and several amino acids, including glutamate and glutamine. In accordance, MCT8-expressing COS-1 cells had 2.2-times lower intracellular accumulation of [125I]-DIT compared with control cells. This effect was largely blocked in the presence of 3,3',5-triiodothyronine (T3) (IC50: 2.5 ± 1.5 µM) or thyroxine (T4) (IC50: 5.8 ± 1.3 µM). Conversely, increasing concentrations of DIT enhanced the accumulation of T3 and T4. The MCT8-specific inhibitor silychristin increased the intracellular accumulation of DIT in human fibroblasts. COS-1 cells expressing MCT8 also exhibited a 50% reduction in intracellular accumulation of [125I]-3-monoiodotyrosine (MIT). In contrast, COS-1 cells expressing MCT8 did not alter the intracellular accumulation of [3H]-glutamate or [3H]-glutamine. However, studies in human fibroblasts showed a 1.5-1.9 times higher glutamate uptake in control fibroblasts compared with fibroblasts derived from patients with MCT8 deficiency, which was not affected in the presence of silychristin. Conclusions: Taken together, our results suggest that the iodotyrosines DIT and MIT can be exported by MCT8. MIT and DIT interfere with MCT8-mediated transport of thyroid hormone in vitro and vice versa. Future studies should elucidate if MCT8, being highly expressed in thyroidal follicular cells, also transports iodotyrosines in vivo.

Genomic-assisted breeding for climate-smart coffee.

Coffee is a universal beverage that drives a multi-industry market on a global basis. Today, the sustainability of coffee production is threatened by accelerated climate changes. In this work, we propose the implementation of genomic-assisted breeding for climate-smart coffee in Coffea canephora. This species is adapted to higher temperatures and is more resilient to biotic and abiotic stresses. After evaluating two populations, over multiple harvests, and under severe drought weather condition, we dissected the genetic architecture of yield, disease resistance, and quality-related traits. By integrating genome-wide association studies and diallel analyses, our contribution is four-fold: (i) we identified a set of molecular markers with major effects associated with disease resistance and post-harvest traits, while yield and plant architecture presented a polygenic background; (ii) we demonstrated the relevance of nonadditive gene actions and projected hybrid vigor when genotypes from different geographically botanical groups are crossed; (iii) we computed medium-to-large heritability values for most of the traits, representing potential for fast genetic progress; and (iv) we provided a first step toward implementing molecular breeding to accelerate improvements in C. canephora. Altogether, this work is a blueprint for how quantitative genetics and genomics can assist coffee breeding and support the supply chain in the face of the current global changes.

Colletotrichum lindemuthianum exhibits different patterns of nuclear division at different stages in its vegetative life cycle.

Live-cell imaging with fluorescent protein labeling is providing major new insights into nuclear dynamics in filamentous fungi. With this approach we provide a detailed report of nuclear organization and behavior during mitosis in the bean pathogen Colletotrichum lindemuthianum. Nuclear division and nuclear migration were analyzed in ungerminated conidia, conidial germlings and the mature colony. Ungerminated conidia were uninucleate and completion of mitosis was found not to be essential for germ tube formation, conidial anastomosis tube (CAT) formation or fusion. Nuclei in fused conidial germlings exhibited asynchronous mitoses, and nuclear migration through fused CATs occurred after the nuclei had divided. Different patterns of nuclear division were found in vegetative hyphae of the mature colony. Synchronous, parasynchronous and asynchronous patterns of mitosis were observed in apical hyphal compartments at the colony border, while only synchronous and asynchronous mitoses occurred in subapical hyphal compartments. These findings have revealed unexpected diversity in the patterns of mitosis in different cells of C. lindemuthianum.

Oral hygiene self-care: Concept analysis for the development of a new nursing diagnosis.

OBJECTIVE: This study aims to analyze the concept of oral hygiene self-care and develop a new problem-focused nursing diagnosis (ND) based on the NANDA-I terminology. METHOD: A concept analysis was performed based on the Walker and Avant framework, including a scoping review phase according to the Joanna Briggs Institute guidelines. Searches were performed in PubMed, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Virtual Health Library, and specific gray literature databases. The development of the diagnostic structure followed the NANDA-I guidelines with a focus on Orem's self-care theory. RESULTS: Including 51 studies, the analysis facilitated the formulation of attributes, antecedents, and consequences of oral hygiene self-care. The ND "Oral hygiene self-care deficit" was created and included 17 defining characteristics, 9 related factors, 5 associated conditions, and 5 high-risk populations. Two cases were constructed to illustrate the use of key terms. CONCLUSIONS: The conceptual analysis provided insight into the concept of oral hygiene self-care and supported the structure of a new ND. IMPLICATIONS FOR NURSING PRACTICE: This study contributes to the implementation of the nursing process by focusing on the identification of individuals with oral hygiene self-care deficit. It will facilitate the promotion of oral health, thereby impacting the individual's quality of life. In addition, it will aid in the development of public policy for the prevention of oral diseases.

Validation of the hospital resources assessment scale for the preservation of urinary continence in the elderly.

OBJECTIVES: to validate the internal structure of the Hospital Resources Assessment Scale for the Preservation of Urinary Continence in the Elderly. METHODS: validation study of the internal structure of a scale constructed based on the Donabedian conceptual model and an integrative review, with prior content validation. The scale was applied to the target population, and 124 nurses responded to the questionnaire. Exploratory Factor Analysis was performed using the FACTOR software, employing multiple techniques. RESULTS: a factorial model with 11 items organized into two dimensions (support for human resources and material resources) was obtained. The "physical structure" dimension was removed from the initial model and adopted as a complementary checklist to the instrument, as it was not possible to obtain a factorable model with this dimension. CONCLUSIONS: we provide a valid scale that can measure indicators, identifying weaknesses and/or strengths related to hospital resources for the preservation of urinary continence in the elderly.