Stretch-induced compliance mechanism in pregnancy-induced cardiac hypertrophy and the impact of cardiovascular risk factors.

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

The link between obesity and the gut microbiota and immune system in early-life.

In early-life, the gut microbiota is highly modifiable, being modulated by external factors such as maternal microbiota, mode of delivery, and feeding strategies. The composition of the child's gut microbiota will deeply impact the development and maturation of its immune system, with consequences for future health. As one of the main sources of microorganisms to the child, the mother represents a crucial factor in the establishment of early-life microbiota, impacting the infant's wellbeing. Recent studies have proposed that dysbiotic maternal gut microbiota could be transmitted to the offspring, influencing the development of its immunity, and leading to the development of diseases such as obesity. This paper aims to review recent findings in gut microbiota and immune system interaction in early-life, highlighting the benefits of a balanced gut microbiota in the regulation of the immune system.

Cardiovascular risk factors during pregnancy impact the postpartum cardiac and vascular reverse remodeling.

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.

Rapid and sustainable HPLC method for the determination of uremic toxins in human plasma samples.

Protein-bound uremic toxins, mainly indoxyl sulfate (3-INDS), p-cresol sulfate (pCS), and indole-3-acetic acid (3-IAA) but also phenol (Pol) and p-cresol (pC), are progressively accumulated during chronic kidney disease (CKD). Their accurate measurement in biomatrices is demanded for timely diagnosis and adoption of appropriate therapeutic measures. Multianalyte methods allowing the establishment of a uremic metabolite profile are still missing. Hence, the aim of this work was to develop a rapid and sensitive method based on high-performance liquid chromatography with fluorescence detection for the simultaneous quantification of Pol, 3-IAA, pC, 3-INDS, and pCS in human plasma. Separation was attained in 12 min, using a monolithic C18 column and isocratic elution with acetonitrile and phosphate buffer containing an ion-pairing reagent, at a flow rate of 2 mL min-1. Standards were prepared in plasma and quantification was performed using the background subtraction approach. LOQ values were ≤ 0.2 µg mL-1 for all analytes except for pCS (LOQ of 2 µg mL-1). The method proved to be accurate (93.5-112%) and precise (CV ≤ 14.3%). The multianalyte application of the method, associated to a reduced sample volume (50 µL), a less toxic internal standard (eugenol) in comparison to the previously applied 2,6-dimethylphenol and 4-ethylphenol, and a green extraction solvent (ethanol), resulted in the AGREE score of 0.62 which is in line with the recent trend of green and sustainable analytical chemistry. The validated method was successfully applied to the analysis of plasma samples from control subjects exhibiting normal levels of uremic toxins and CKD patients presenting significantly higher levels of 3-IAA, pC, 3-INDS, and pCS that can be further investigated as biomarkers of disease progression.

Oral microbiome characterization in oral mucositis patients-A systematic review.

BACKGROUND: Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore, this systematic review aims to characterize the oral dysbiosis associated with OM. METHODS: The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical studies characterizing the oral microbiome alterations in patients with OM. RESULTS: From a total of 2500 articles retrieved, we included nine articles in this systematic review. Certain types of bacteria, as Fusobacterium, were recognized as predictors of the onset of OM. In addition, it was reported that patients with severe OM presented a reduction in alpha-diversity, an increase in beta-diversity. The abundance of some taxa significantly changed with OM severity, with Bacillota phylum and genera Leptotrichia, Actinomyces, and Prevotella decreasing and Treponema increasing with disease progression. Additionally, during cancer treatment, changes in the oral microbiome have been observed in OM patients, with an increase in Candida and nosocomial pathogens, including Staphylococcus species. CONCLUSION: Our review indicates that cancer treatment can significantly alter the oral microbiome, with more pronounced changes observed in patients with severe OM in all relevant oral phyla, but more pronounced in Bacillota phylum.

Pseudomonadota in the oral cavity: a glimpse into the environment-human nexus.

The phylum Pseudomonadota is amongst the most represented in the environment, with a comparatively lower prevalence in the human oral cavity. The ubiquity of Pseudomonadota and the fact that the oral cavity is the most likely entry portal of bacteria from external sources underlie the need to better understand its occurrence in the interface environment-humans. Yet, the relevance oral Pseudomonadota is largely underexplored in the scientific literature, a gap that this review aims at addressing by making, for the first time, an overview of the diversity and ecology of Pseudomonadota in the oral cavity. The screening of scientific literature and human microbiome databases unveiled 1328 reports of Pseudomonadota in the oral cavity. Most of these belonged to the classes Beta- and Gammaproteobacteria, mainly to the families Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae. Others also regularly reported include genera such as Enterobacter, Klebsiella, Acinetobacter, Escherichia, Burkholderia, or Citrobacter, whose members have high potential to acquire virulence and antibiotic resistance genes. This review provides evidence that clinically relevant environmental Pseudomonadota may colonize humans via oral cavity. The need for further investigation about Pseudomonadota at the environment-oral cavity interface and their role as vectors potentially involved in virulence and antibiotic resistance transmission is demonstrated. KEY POINTS: • Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae are part of the core oral microbiome • Enterobacteriaceae, Acinetobacter, or Burkholderia are frequent in the oral microbiome • Gut dysbiosis may be associated with colonization by ubiquitous oral Pseudomonadota.

Vertical Transmission and Antifungal Susceptibility Profile of Yeast Isolates from the Oral Cavity, Gut, and Breastmilk of Mother-Child Pairs in Early Life.

Yeast acquisition begins at birth; however, the contribution of the mother on yeast transmission to the offspring and associated resistance is yet to be clarified. The aim of this study was to explore the vertical transmission of yeasts and their antifungal susceptibility profile in early life. Oral, fecal, and breastmilk samples were collected from 73 mother-child pairs four to twelve weeks after delivery and cultured on Sabouraud dextrose agar with chloramphenicol. The isolates were identified by MALDI-TOF MS. The vertical transmission was studied by microsatellite genotyping. Antifungal susceptibility was determined for fluconazole, voriconazole, miconazole, anidulafungin, and nystatin by broth microdilution assay, following CLSI-M60 guidelines. A total of 129 isolates were identified from 53% mother-child pairs. We verified the vertical transmission of Candida albicans (n = three mother-child pairs) and Candida parapsilosis (n = one mother-child pair) strains, including an antifungal resistant strain transmitted from breastmilk to the gut of a child. Most isolates were susceptible to the tested antifungals, with the exception of four C. albicans isolates and one R. mucilaginosa isolate. The vertical transmission of yeasts happens in early life. This is the first work that demonstrated the role of the mother as a source of transmission of antifungal-resistant yeasts to the child.

Microbiology and postmortem interval: a systematic review.

This systematic review aims to learn if and how it is possible to use the human microbiome to indicate the time elapsed after death. Articles were searched on the PubMed database using predefined data fields and keywords; reviews, systematic reviews, and meta-analyses were excluded. The final selection included 14 papers (out of 144). The results indicated that the microorganisms present in the cadaveric island succeed predictably over time, with markers between the stages of decomposition constituting a potential innovative tool for postmortem interval (PMI) estimation. The human microbiome has the potential to be used for PMI estimation and may present advantages as microbes are present in all seasons, in all habitats, including the most extreme ones, and because microbial communities respond predictably to environmental changes.

Fungal Genomes and Genotyping.

The availability of complete fungal genomes is expanding rapidly and is offering an extensive and accurate view of this "kingdom." The scientific milestone of free access to more than 1000 fungal genomes of different species was reached, and new and stimulating projects have meanwhile been released. The "1000 Fungal Genomes Project" represents one of the largest sequencing initiative regarding fungal organisms trying to fill some gaps on fungal genomics. Presently, there are 329 fungal families with at least one representative genome sequenced, but there is still a large number of fungal families without a single sequenced genome. In addition, additional sequencing projects helped to understand the genetic diversity within some fungal species. The availability of multiple genomes per species allows to support taxonomic organization, brings new insights for fungal evolution in short-time scales, clarifies geographical and dispersion patterns, elucidates outbreaks and transmission routes, among other objectives. Genotyping methodologies analyze only a small fraction of an individual's genome but facilitate the comparison of hundreds or thousands of isolates in a small fraction of the time and at low cost. The integration of whole genome strategies and improved genotyping panels targeting specific and relevant SNPs and/or repeated regions can represent fast and practical strategies for studying local, regional, and global epidemiology of fungi.

The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis.

Chronic kidney disease (CKD) is associated with an imbalanced human microbiome due not only to CKD-associated factors such as uremia, increased inflammation and immunosuppression, but also to pharmacological therapies and dietary restrictions. End-stage renal disease patients require renal replacement therapies commonly in the form of hemodialysis (HD) or peritoneal dialysis (PD). HD implies the existence of a vascular access, such as an arteriovenous fistula/graft or a venous catheter, whereas PD implies a long-term peritoneal catheter and the constant inflow of peritoneal dialysate. Also, dietary adaptations are mandatory in both therapies. This revision explores the impact of HD or PD therapies on human microbiome. HD and PD appear to be associated with different changes in the gut microbiome, for example a decrease in Proteobacteria relative abundance in HD patients and increase in PD patients. Both therapies may also have an impact on the human microbiome beyond the gut, leading to increased relative abundance of specific bacteria in the blood microbiome of HD patients and increased relative abundance of other bacteria in the peritoneal microbiome of PD patients. HD and PD catheter biofilms may also play an important role in the changes observed in these microbiomes. A more interdisciplinary approach is needed to further clarify the role of microbial groups other than bacteria in all body habitats to allow the complete understanding of the impact of HD or PD on the microbiome of CKD patients. Moreover, strategies that promote a healthy balance of the human microbiome on these patients should be explored.

Determination of Azole Resistance and TR34/L98H Mutations in Isolates of Aspergillus Section Fumigati from Turkish Cystic Fibrosis Patients.

BACKGROUND: Aspergillus fumigatus is the species section Fumigati most frequently isolated from the respiratory tract of cystic fibrosis (CF) patients. Recent studies suggest that mutations in the Cyp51 gene, particularly TR34/L98H, are responsible for azole resistance. OBJECTIVES AND METHODS: The focus of this study was on section Fumigati isolates isolated from the respiratory tract samples of CF patients. More specifically, the goal was to detect A. fumigatus isolates, test their antifungal susceptibility to itraconazole, voriconazole and posaconazole, and finally determine the presence of TR34/L98H and other mutations in the isolates Cyp51A gene. RESULTS AND CONCLUSIONS: A set of 31 isolates of Aspergillus section Fumigati were obtained from the sputum samples of 6 CF patients and subsequently identified to species level by microsatellite genotyping. All isolates were determined as A. fumigatus and involved 14 different genotypes. The minimal inhibitory concentrations to the three azoles were determined by the E-test method, and the Cyp51A gene was sequenced. One of the genotypes was found to be resistant to all azoles but no mutations were detected in the Cyp51A gene, especially the TR34/L98H mutation. Therefore, mutations in genes other than Cyp51A or other distinct mechanisms may be responsible for this reported multiazole resistance found in a Turkish CF patient.

Oral Colonization of Staphylococcus Species in a Peritoneal Dialysis Population: A Possible Reservoir for PD-Related Infections?

Peritoneal dialysis-related infections are important morbidity/mortality causes, being staphylococci the most prevalent agents. Since Staphylococcus aureus nasopharynx carriage is a known risk factor for PD infections and the oral cavity is a starting point for systemic diseases development, we aimed at comparing the oral staphylococci colonization between PD patients and controls and studying the association with PD-related infections. Saliva samples were plated in Mannitol salt, and isolates were identified by DnaJ gene sequencing. Staphylococci PD-related infections were recorded throughout the 4-year period following sample collection. Staphylococcus colonization was present in >90% of the samples from both groups (a total of nine species identified). PD patients presented less diversity and less prevalence of multispecies Staphylococcus colonization. Although all patients presenting Staphylococcus epidermidis PD-related infections were also colonized in the oral cavity by the same agent, only 1 out of 7 patients with ESI caused by S. aureus presented S. aureus oral colonization. Staphylococci are highly prevalent in the oral cavity of both groups, although PD patients presented less species diversity. The association between oral Staphylococcus carriage and PD-related infections was present for S. epidermidis but was almost inexistent for S. aureus, so, further studies are still necessary to evaluate the infectious potential of oral Staphylococcus carriage in PD.

Oral Yeast Colonization and Fungal Infections in Peritoneal Dialysis Patients: A Pilot Study.

Peritonitis and exit-site infections are important complications in peritoneal dialysis (PD) patients that are occasionally caused by opportunistic fungi inhabiting distant body sites. In this study, the oral yeast colonization of PD patients and the antifungal susceptibility profile of the isolated yeasts were accessed and correlated with fungal infection episodes in the following 4 years. Saliva yeast colonization was accessed in 21 PD patients and 27 healthy controls by growth in CHROMagar-Candida® and 18S rRNA/ITS sequencing. PD patients presented a lower oral yeast prevalence when compared to controls, namely, Candida albicans. Other species were also isolated, Candida glabrata and Candida carpophila. The antifungal susceptibility profiles of these isolates revealed resistance to itraconazole, variable susceptibility to caspofungin, and higher MIC values of posaconazole compared to previous reports. The 4-year longitudinal evaluation of these patients revealed Candida parapsilosis and Candida zeylanoides as PD-related exit-site infectious agents, but no correlation was found with oral yeast colonization. This pilot study suggests that oral yeast colonization may represent a limited risk for fungal infection development in PD patients. Oral yeast isolates presented a variable antifungal susceptibility profile, which may suggest resistance to some second-line drugs, highlighting the importance of antifungal susceptibility assessment in the clinical practice.

Renalase regulates peripheral and central dopaminergic activities.

Renalase is a recently identified FAD/NADH-dependent amine oxidase mainly expressed in kidney that is secreted into blood and urine where it was suggested to metabolize catecholamines. The present study evaluated central and peripheral dopaminergic activities in the renalase knockout (KO) mouse model and examined the changes induced by recombinant renalase (RR) administration on plasma and urine catecholamine levels. Compared with wild-type (WT) mice, KO mice presented increased plasma levels of epinephrine (Epi), norepinephrine (NE), and dopamine (DA) that were accompanied by increases in the urinary excretion of Epi, NE, DA. In addition, the KO mice presented an increase in urinary DA-to-l-3,4-dihydroxyphenylalanine (l-DOPA) ratios without changes in renal tubular aromatic-l-amino acid decarboxylase (AADC) activity. By contrast, the in vivo administration of RR (1.5 mg/kg sc) to KO mice was accompanied by significant decreases in plasma levels of Epi, DA, and l-DOPA as well as in urinary excretion of Epi, DA, and DA-to-l-DOPA ratios notwithstanding the accompanied increase in renal AADC activity. In addition, the increase in renal DA output observed in renalase KO mice was accompanied by an increase in the expression of the L-type amino acid transporter like (LAT) 1 that is reversed by the administration of RR in these animals. These results suggest that the overexpression of LAT1 in the renal cortex of the renalase KO mice might contribute to the enhanced l-DOPA availability/uptake and consequently to the activation of the renal dopaminergic system in the presence of renalase deficiency.

Interindividual variability and intraindividual stability of oral fungal microbiota over time.

Oral microbiota is one of the most complex and diverse microbial communities in the human body. In the present study, we aimed to characterize oral fungi biodiversity and stability over time in a group of healthy participants with good oral health. Oral health and oral fungal microbiota were evaluated in 40 healthy individuals. A follow-up of 10 participants was carried out 28 weeks and 30 weeks after the first sampling. Oral rinse was collected and incubated in a fungal selective medium at 25ºC and 37ºC for 7 days. Fungi were identified based on macro- and microscopic morphology. API/ID32C was used for yeast identification, and molecular techniques were used to identify the most prevalent nonidentified moulds, mainly by sequencing 18S and internally transcribed spacer regions. Moulds were recovered from all participants and yeast from 92.5%. The most frequently isolated fungi were Candida spp., Rhodotorula spp., Penicillium spp., Aspergillus spp., and Cladosporium spp. The oral fungal community presented a high interindividual variability, but the frequency and quantification of each fungal taxon was constant over the 30-week observation period, showing a consistent intraindividual stability over time. The intraindividual stability opposed to interindividual variability may suggest a common and a variable group of fungi in the oral cavity.

Emotion dysregulation and depressive symptoms mediate the association between inhibitory control difficulties and aggressive behaviour in children with ADHD.

Background/objectives: Impulsive aggressive behaviour, although not a core symptom, is often part of the clinical presentation of attention-deficit/hyperactivity disorder (ADHD). Recently, impulsive aggression has been attributed to emotion dysregulation, which is currently conceptualised as a transdiagnostic factor and seems to contribute to the co-occurrence of other problems in ADHD. Thus, this study investigated the presence of impulsive aggressive behaviour and explored whether emotion dysregulation mediates the relationship between inhibitory control difficulties and aggressive behaviour in children with ADHD. Because ADHD may act as a risk factor for the development of other conditions, such as internalising problems, we aimed to understand whether depressive symptoms contribute to this relationship. Methods: Seventy-two children were recruited from a hospital and the community, 38 of whom had ADHD and 34 were typically developing (TD). Parents completed the Child Behaviour Checklist, the Behaviour Rating Inventory of Executive Function, and the Emotion Regulation Checklist. Simple mediation and serial mediation models were performed to test our hypotheses. Results: Aggressive behaviour was significantly higher in ADHD children compared to TD children. Emotion dysregulation fully mediated the relationship between inhibitory control difficulties and aggressive behaviour in ADHD children. Adding depressive symptoms to the model increased the explained variance in aggressive behaviour. Conclusion: The main result of our study supports the role of emotion dysregulation and depressive symptoms in mediating the relationship between inhibitory control difficulties and impulsive aggressive behaviour in children with ADHD. This highlights that aggressive behaviour is, in part, a result of the inability of the child to appropriately regulate their emotions. Future interventions may be tailored to improve emotion regulation skills to address aggressive behaviour.

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis.

Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.

The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis.

INTRODUCTION AND OBJECTIVES: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters. MATERIALS AND METHODS: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universitário de São João (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3-V4 region of the bacterial 16S rRNA gene. Correlations with the patients' clinical data and inflammatory profile were performed. RESULTS: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups. Depletion of Gardnerella, Staphylococcus, Corynebacterium, Lactobacillus or Dermabacter populations correlated with CKD-PD patients with history of diabetes, history of peritonitis and altered levels of sCD14. CONCLUSIONS: Our results highlight urogenital microbiome as a potential partner and/or marker in the overall health state of CKD-PD patients.

The impact of echocardiographic indexation to evaluate cardiac reverse remodeling throughout pregnancy and postpartum.

INTRODUCTION AND OBJECTIVES: Echocardiography guidelines suggest normalizing left ventricular (LV) volumes and mass (LVM) to body size. During pregnancy, continuous weight variation impacts on body surface area (BSA) calculation, limiting the longitudinal analysis of cardiac remodeling (CR) and reverse remodeling (RR) variables. Our aim was to identify the most common indexing methodologies in the literature on pregnant populations through a systematic review; and, to compare four scaling methods: (i) none (absolute values); (ii) indexing to the BSA before pregnancy; (iii) allomeric indexing; and (iv) indexing to BSA measured at the same day of cardiac assessment, using an illustrative example. METHODS: We performed a systematic review of CR and RR during pregnancy and post-partum, using two databases. We included studies reporting longitudinal echocardiographic analysis of cardiac chamber volumes in humans. We used a prospective cohort study of healthy pregnant women who underwent four echocardiographic evaluations during pregnancy and postpartum, as an illustrative example. RESULTS: Twenty-seven studies were included, most studies indexed to BSA measured at each evaluation moment (n=21). Within-subjects design was the most reported to analyse longitudinal data (n=17). Indexation to the pre-pregnancy BSA or application of allometric indexes revealed a higher effect than BSA measured at each evaluation and an equal effect to not indexing using within-subjects design. The within-subjects designs also revealed a higher effect size value than the between-subjects design for longitudinal analysis of LVM adaptations during pregnancy and postpartum. CONCLUSION(S): This study concludes that indexation methods do not impact the clinical interpretation of longitudinal echocardiographic assessment but highlights the need to harmonize normalization procedures during pregnancy.

Renalase regulates renal dopamine and phosphate metabolism.

Renalase is a kidney-secreted catecholamines-degrading enzyme whose expression and activity are downregulated by increased dietary phosphate. A renalase knockout (KO) mouse model was used to explore the mechanisms mediating renalase's effect on phosphate excretion. Compared with wild-type (WT) mice maintained on a regular diet, KO mice show decreased serum PO4(-) (KO = 5.3 ± 0.2 vs. WT = 6.0 ± 0.1, n = 6; P < 0.04) and increased urinary PO4(-) excretion (urine PO4(-)/creatinine: KO = 7.7 ± 0.3 vs. WT = 6.1 ± 0.3, n = 6; P < 0.02). However, both WT and KO mice respond similarly to PO4(-) restriction by increasing renal COMT-1 activity and markedly decreasing PO4(-) excretion, which excludes an intrinsic renal defect in the KO. Renal sodium-phosphate cotransporter Npt2a, sodium proton exchanger NHE3 expression, and MAO-A and B activity did not differ between WT and KO. Only catechol-O-methyl transferase (COMT) expression and activity were significantly increased in KO mice. Despite that, urinary dopamine increased by twofold, whereas urinary l-DOPA excretion decreased by twofold in the KO mouse, indicating an upregulation of renal dopamine (DA) synthesis. These data indicate that renalase deficiency is associated with increased renal DA synthesis, stimulated PO4(-) excretion, and moderately severe hypophosphatemia. The signal to increase renal DA synthesis is strong since it overcomes a compensatory increase in COMT activity.