Stating asymmetry in neural pathways: methodological trends in autonomic neuroscience.

Aim: Many particularities concerning interhemispheric differences still need to be explored and unveiled. Functional and anatomical differential features found between left and right brain sides are best known as asymmetries and are consequence of the unilateral neuronal recruitment or predominance that is set to organize some function. The outflow from different neural pathways involved in the autonomic control of the cardiovascular system may route through asymmetrically relayed efferences (ipsilateral/lateralized and/or contralateral). In spite of this, the literature reporting on the role of central nuclei involved in the autonomic control is not always dedicated on these interhemispheric comparisons. Considering the recent reports demonstrating that asymmetries may set differential functional responses, it is worth checking differences between right and left sides of central regions. This review aims to inspire neuroscientists with the idea that studying the interhemispheric differences may deepen the understanding on several centrally controlled responses, with special regard to the autonomic functions underlying the cardiovascular regulation. Conclusions: Thus, an avenue of knowledge may unfold from a field of research that requires further exploration.

Wickerhamiella dulcicola sp. nov. and Wickerhamiella cachassae sp. nov., yeasts isolated from cachaça fermentation in Brazil.

Six strains of two novel yeast species were isolated from sugar-cane juice and fermentation vats of cachaça production in Brazil. The sequences of the D1/D2 domains of the large-subunit rRNA gene showed that these species belong to the Wickerhamiella clade, and their closest described relative in terms of sequence similarity is Candida (iter. nom. Wickerhamiella) drosophilae. The type strain of Wickerhamiella cachassae sp. nov. is UFMG-D5L7(T) ( = CBS 12587(T)  = CBMAI 1469(T)) and the type strain of Wickerhamiella dulcicola sp. nov. is UFMG-TOL15(T) ( = CBS 12588(T)  = CBMAI 1468(T)).

A peptide fraction from hardened common beans (Phaseolus vulgaris) induces endothelium-dependent antihypertensive and renal effects in rats.

Beans reached the research spotlight as a source of bioactive compounds capable of modulating different functions. Recently, we reported antioxidant and oxidonitrergic effect of a low molecular weight peptide fraction (<3 kDa) from hardened bean (Phaseolus vulgaris) in vitro and ex vivo, which necessitate further in vivo assessments. This work aimed to evaluate the hypotensive effect and the involved physiological mechanisms of the hardened common bean peptide (Phaseolus vulgaris) in normotensive (Wistar) and hypertensive (SHR) animals. Bean flour was combined with a solution containing acetonitrile, water and formic acid (25: 24: 1). Protein extract (PV3) was fractioned (3 kDa membrane). We assessed PV3 effects on renal function and hemodynamics of wistar (WT-normotensive) and spontaneously hypertensive rats (SHR) and measured systemic arterial pressure and flow in aortic and renal beds. The potential endothelial and oxidonitrergic involvements were tested in isolated renal artery rings. As results, we found that PV3: I) decreased food consumption in SHR, increased water intake and urinary volume in WT, increased glomerular filtration rate in WT and SHR, caused natriuresis in SHR; II) caused NO- and endothelium-dependent vasorelaxation in renal artery rings; III) reduced arterial pressure and resistance in aortic and renal vascular beds; IV) caused antihypertensive effects in a dose-dependent manner. Current findings support PV3 as a source of bioactive peptides and raise the potential of composing nutraceutical formulations to treat renal and cardiovascular diseases.

Are hemoglobin-derived peptides involved in the neuropsychiatric symptoms caused by SARS-CoV-2 infection?

Follow-up of patients affected by COVID-19 has unveiled remarkable findings. Among the several sequelae caused by SARS-CoV-2 viral infection, it is particularly noteworthy that patients are prone to developing depression, anxiety, cognitive disorders, and dementia as part of the post-COVID-19 syndrome. The multisystem aspects of this disease suggest that multiple mechanisms may converge towards post-infection clinical manifestations. The literature provides mechanistic hypotheses related to changes in classical neurotransmission evoked by SARS-CoV-2 infection; nonetheless, the interaction of peripherally originated classical and non-canonic peptidergic systems may play a putative role in this neuropathology. A wealth of robust findings shows that hemoglobin-derived peptides are able to control cognition, memory, anxiety, and depression through different mechanisms. Early erythrocytic death is found during COVID-19, which would cause excess production of hemoglobin-derived peptides. Following from this premise, the present review sheds light on a possible involvement of hemoglobin-derived molecules in the COVID-19 pathophysiology by fostering neuroscientific evidence that supports the contribution of this non-canonic peptidergic pathway. This rationale may broaden knowledge beyond the currently available data, motivating further studies in the field and paving ways for novel laboratory tests and clinical approaches.

Angiotensin-(1-7) attenuates the negative inotropic response to acetylcholine in the heart.

Previous studies have suggested that the Angiotensin-(1-7) [(Ang-(1-7)] can change cardiac function by modulating the autonomic nervous system. However, it is unknown whether the Ang-(1-7) can modulate the effect of acetylcholine (ACh) in ventricular contractility. Thus, this study aimed to investigate whether Ang-(1-7) modifies the amplitude of the cardiac cholinergic effects and if these effects are intrinsic to the heart. In anesthetized Wistar rats, Ang-(1-7) attenuated the effect of ACh in decreasing the left ventricular end-systolic pressure (LVESP), dP/dtmax, and dP/dtmin, but did not modify the hypotensive effect of ACh. Similarly, Ang-(1-7) attenuated the reduction of the LVESP, dP/dtmax, and dP/dtmin evoked by ACh in isolated hearts. These effects were blocked by the Mas receptor antagonist, A-779, but not by the adenylyl cyclase inhibitor MDL-12,330 A. Ang-(1-7) also attenuated the reduction in the maximum contraction and relaxation speeds and the shortening promoted by ACh in isolated cardiomyocytes. These data show that Ang-(1-7) acting through Mas receptor counter-regulates the myocardial contractile response to ACh in an arterial pressure and heart rate-independent manner.

Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19.

Introduction: The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective: Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results: Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion: The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats.

The endocannabinoid neurotransmission acting via local CB1 receptor in the bed nucleus of the stria terminalis (BNST) has been implicated in behavioral and physiological responses to emotional stress. However, the neural network related to this control is poorly understood. In this sense, the lateral hypothalamus (LH) is involved in stress responses, and BNST GABAergic neurons densely innervate this hypothalamic nucleus. However, a role of BNST projections to the LH in physiological responses to stress is unknown. Therefore, using male rats, we investigated the role of LH GABAergic neurotransmission in the regulation of cardiovascular responses to stress by CB1 receptors within the BNST. We observed that microinjection of the selective CB1 receptor antagonist AM251 into the BNST decreased the number of Fos-immunoreactive cells within the LH of rats submitted to acute restraint stress. Treatment of the BNST with AM251 also enhanced restraint-evoked tachycardia. Nevertheless, arterial pressure increase and sympathetically-mediated cutaneous vasoconstriction to restraint was not affected by CB1 receptor antagonism within the BNST. The effect of AM251 in the BNST on restraint-evoked tachycardia was abolished in animals pretreated with the selective GABAA receptor antagonist SR95531 in the LH. These results indicate that regulation of cardiovascular responses to stress by CB1 receptors in the BNST is mediated by GABAergic neurotransmission in the LH. Present data also provide evidence of the BNST endocannabinoid neurotransmission as a mechanism involved in LH neuronal activation during stressful events.

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity.

Clonidine (CL) and Rilmenidine (RI) are among the most frequently prescribed centrally acting antihypertensives. Here, we compared CL and RI effects on psychogenic cardiovascular reactivity to sonant, luminous, motosensory, and vibrotactile stimuli during neurogenic hypertension. The femoral artery and vein of Wistar (WT - normotensive) and spontaneously hypertensive rats (SHR) were catheterized before (24 h interval) i.p. injection of vehicle (NaCl 0.9%, control - CT group), CL (10 µg/kg), or RI (10 µg/kg) and acute exposure to luminous (5000 lm), sonant (75 dB sudden tap), motor (180° cage twist), and air-jet (10 L/min - restraint and vibrotactile). Findings showed that: (i) CL or RI reduced the arterial pressure of SHR, without affecting basal heart rate in WT and SHR; (ii) different stimuli evoked pressor and tachycardic responses; (iii) CL and RI reduced pressor response to sound; (iv) CL or RI reduced pressor responses to luminous stimulus without a change in peak tachycardia in SHR; (v) cage twist increased blood pressure in SHR, which was attenuated by CL or RI; (vi) air-jet increased pressure and heart rate; (vii) CL or RI attenuated the pressor responses to air-jet in SHR while RI reduced the chronotropic reactivity in both strains. Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air-jet-induced tachycardia.

Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.

Ghrelin is a peptide hormone whose effects are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), mainly expressed in the brain but also in kidneys. The hypothesis herein raised is that GHS-R1a would be player in the renal contribution to the neurogenic hypertension pathophysiology. To investigate GHS-R1a role on renal function and hemodynamics, we used Wistar (WT) and spontaneously hypertensive rats (SHR). First, we assessed the effect of systemically injected vehicle, ghrelin, GHS-R1a antagonist PF04628935, ghrelin plus PF04628935 or GHS-R1a synthetic agonist MK-677 in WT and SHR rats housed in metabolic cages (24 h). Blood and urine samples were also analyzed. Then, we assessed the GHS-R1a contribution to the control of renal vasomotion and hemodynamics in WT and SHR. Finally, we assessed the GHS-R1a levels in brain areas, aorta, renal artery, renal cortex and medulla of WT and SHR rats using western blot. We found that ghrelin and MK-677 changed osmolarity parameters of SHR, in a GHS-R1a-dependent manner. GHS-R1a antagonism reduced the urinary Na+ and K+ and creatinine clearance in WT but not in SHR. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a protein levels were decreased in the kidney and brain areas of SHR when compared to WT. Therefore, GHS-R1a role in the control of renal function and hemodynamics during neurogenic hypertension seem to be different, and this may be related to brain and kidney GHS-R1a downregulation.

Behavioral effects evoked by the beta globin-derived nonapeptide LVV-H6.

LVV-hemorphin-6 (LVV-h6) is bioactive peptide and is a product of the degradation of hemoglobin. Since LVV-h6 effects are possibly mediated by opioid or AT4/IRAP receptors, we hypothesized that LVV-h6 would modify behavior. We evaluated whether LVV-h6 affects: i) anxiety-like behavior and locomotion; ii) depression-like behavior; iii) cardiovascular and neuroendocrine reactivity to emotional stress. Male Wistar rats ( ± 300 g) received LVV-h6 (153 nmol/kg i.p.) or vehicle (NaCl 0.9% i.p.). We used: i) open field (OF) test for locomotion; ii) elevated plus maze (EPM) for anxiety-like behavior; iii) forced swimming test (FST) for depression-like behavior and iv) air jet for cardiovascular and neuroendocrine reactivity to stress. Diazepam (2 mg/kg i.p.) and imipramine (15 mg/kg i.p.) were used as positive control for EPM and FST, respectively. To evaluate the LVV-h6 mechanisms, we used: the antagonist of oxytocin (OT) receptors (atosiban - ATS 1 and 0.1 mg/kg i.p.); the inhibitor of tyrosine hydroxylase (Alpha-methyl-p-tyrosine - AMPT 200 mg/kg i.p.) to investigate the involvement of catecholaminergic paths; and the antagonist of opioid receptors (naltrexone - NTX 0.3 mg/kg s.c.). We found that LVV-h6: i) evoked anxiolytic-like effect; ii) evoked antidepressant-like effect in the FST; and iii) did not change the locomotion, neuroendocrine and cardiovascular responses to stress. The LVV-h6 anxiolytic-like effect was not reverted by ATS and AMPT. However, the antidepressant effects were reverted only by NTX. Hence, our findings demonstrate that LVV-h6 modulates anxiety-like behavior by routes that are not oxytocinergic, catecholaminergic or opioid. The antidepressant-like effects of LVV-h6 rely on opioid pathways.

Involvement of GABAergic and Adrenergic Neurotransmissions on Paraventricular Nucleus of Hypothalamus in the Control of Cardiac Function.

Sympathetic premotor neurons of the paraventricular hypothalamus (PVN) play a role in hemodynamics adjustments during changes in body fluid homeostasis. However, PVN contribution to the tonic control of cardiac function remains to be systematically studied. In this study, we assessed whether GABAergic and adrenergic synapses, known for being active in the PVN, are involved in the control of cardiac function. Adult male Wistar rats (250-350 g; n = 27) were anesthetized with urethane (1.2-1.4 g/kg i.p.) and underwent catheterization of femoral artery to record blood pressure and heart rate. The femoral vein was used to inject the vasoactive agents phenylephrine (10 µg/kg) and sodium nitroprusside (10 µg/kg) and to supplement anesthesia. The cardiac left ventricle was catheterized to record left ventricular pressure and its derivative. Craniotomy allowed for injections (100 nL) into the PVN of: muscimol (20 mM), bicuculline methiodide (0.4 mM), propranolol (10 mM), isoproterenol (100 µM), phentolamine (13 mM), phenylephrine (30 nM). We found that: (i) inhibition of PVN by muscimol, reduced arterial pressure, cardiac chronotropy and inotropy; (ii) disinhibition of PVN neurons by bicuculline evoked positive chronotropy and inotropy, and increase blood pressure; (iii) PVN alpha adrenergic receptors control cardiac chronotropy and inotropy; (iv) beta adrenergic receptors of the PVN do not influence cardiac function; (v) afterload does not contribute to the PVN-evoked inotropy. Our results indicate that the modulation of the activity of PVN neurons exerted by GABAergic and adrenergic mechanisms contribute to the control of cardiac function.

Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. AIMS: In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. MAIN METHODS AND KEY FINDINGS: Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. SIGNIFICANCE: Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors.

Are hemoglobin-derived peptides involved in the neuropsychiatric symptoms caused by SARS-CoV-2 infection?

Follow-up of patients affected by COVID-19 has unveiled remarkable findings. Among the several sequelae caused by SARS-CoV-2 viral infection, it is particularly noteworthy that patients are prone to developing depression, anxiety, cognitive disorders, and dementia as part of the post-COVID-19 syndrome. The multisystem aspects of this disease suggest that multiple mechanisms may converge towards post-infection clinical manifestations. The literature provides mechanistic hypotheses related to changes in classical neurotransmission evoked by SARS-CoV-2 infection; nonetheless, the interaction of peripherally originated classical and non-canonic peptidergic systems may play a putative role in this neuropathology. A wealth of robust findings shows that hemoglobin-derived peptides are able to control cognition, memory, anxiety, and depression through different mechanisms. Early erythrocytic death is found during COVID-19, which would cause excess production of hemoglobin-derived peptides. Following from this premise, the present review sheds light on a possible involvement of hemoglobin-derived molecules in the COVID-19 pathophysiology by fostering neuroscientific evidence that supports the contribution of this non-canonic peptidergic pathway. This rationale may broaden knowledge beyond the currently available data, motivating further studies in the field and paving ways for novel laboratory tests and clinical approaches.

The hemoglobin derived peptide LVV-hemorphin-7 evokes behavioral effects mediated by oxytocin receptors.

LVV-hemorphin-7 (LVV-h7) is bioactive peptide resulting from degradation of hemoglobin ß-globin chain. LVV-h7 is a specific agonist of angiotensin IV receptor. This receptor belongs to the class of insulin-regulated aminopeptidases (IRAP), which displays oxytocinase activity. Herein, our aims were to assess whether: i) LVV-h7 modifies centrally organized behavior and cardiovascular responses to stress and ii) mechanisms underlying LVV-h7 effects involve activation of oxytocin (OT) receptors, probably as result of reduction of IRAP proteolytic activity upon OT. Adult male Wistar rats (270-370g) received (i.p.) injections of LVV-h7 (153nmol/kg), or vehicle (0.1ml). Different protocols were used: i) open field (OP) test for locomotor/exploratory activities; ii) Elevated Plus Maze (EPM) for anxiety-like behavior; iii) forced swimming test (FST) test for depression-like behavior and iv) air jet for cardiovascular reactivity to acute stress exposure. Diazepam (2mg/kg) and imipramine (15mg/kg) were used as positive control for EPM and FST, respectively. The antagonist of OT receptors (OTr), atosiban (1 and 0,1mg/kg), was used to determine the involvement of oxytocinergic paths. We found that LVV-h7: i) increased the number of entries and the time spent in open arms of the maze, an indicative of anxiolysis; ii) provoked antidepressant effect in the FS test; and iii) increased the exploration and locomotion; iv) did not change the cardiovascular reactivity and neuroendocrine responses to acute stress. Also, increases in locomotion and the antidepressant effects evoked by LVV-h7 were reverted by OTr antagonist. We conclude that LVV-h7 modulates behavior, displays antidepressant and anxiolytic effects that are mediated in part by oxytocin receptors.

Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19

Abstract Introduction The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Criança com retinoblastoma atendida em sala de recursos multifuncional - DV / Child stimulation with retinoblastoma in a Multifunctional Resource Room - Visual Disability

O retinoblastoma é um tumor maligno ocular com mais frequência na infância e pode causar a cegueira e a morte. O diagnóstico precoce possibilita alternativas para a saúde e para a educação da criança, em institutos especializados e estimulação precoce em Salas de Recursos Multifuncionais - Deficiência Visual (SRM-DV). O texto a seguir relata um estudo de caso de atendimento sobre o diagnóstico, tratamentos e a evolução, principalmente, do desenvolvimento da visão de uma criança com retinoblastoma, atendida em uma SRM-DV localizada em uma cidade do interior do estado do Paraná. Objetiva-se demonstrar o trabalho de estimulação visual desenvolvido por uma profissional especialista e o envolvimento familiar ao longo dos atendimentos. Por meio de consulta autorizada ao relatório de atendimento, apresenta-se detalhamento sobre o plano de trabalho e o relato do acompanhamento e evolução da criança atendida. Os resultados apresentam ações importantes que foram eficazes no atendimento individual com a criança e apontam a necessidade da continuidade do envolvimento familiar para que as atividades desenvolvidas e sugeridas pela especialista sejam realizadas também fora do ambiente da SRM-DV.

Retinoblastoma is a malignant ocular tumor most frequently in childhood and can cause blindness and death. Early diagnosis provides alternatives for children's health and education, in specialized institutes and early stimulation in Multifunctional Resource Room - Visual Disability. The following text reports a case study of care about diagnosis, treatments and the evolution, mainly, of the development of the vision of a child with retinoblastoma, attended in a Multifunctional Resource Room - Visual Disability located in a city in the interior of the State of Paraná. The objective is to demonstrate the work of visual stimulation developed by a specialist Professional and family involvement throughout the visits. Through authorized consultation of the care report, details about the work plan and the report on the follow-up and evolution of the assisted child are presented. The results show important actions that were effective in individual care with the child and point the need for continued family involvement so that the activities developed and suggested by the specialist are also carried outside the Multifunctional Resource Room - Visual Disability environment.

The sil Locus in Streptococcus Anginosus Group: Interspecies Competition and a Hotspot of Genetic Diversity.

The Streptococcus Invasion Locus (Sil) was first described in Streptococcus pyogenes and Streptococcus pneumoniae, where it has been implicated in virulence. The two-component peptide signaling system consists of the SilA response regulator and SilB histidine kinase along with the SilCR signaling peptide and SilD/E export/processing proteins. The presence of an associated bacteriocin region suggests this system may play a role in competitive interactions with other microbes. Comparative analysis of 42 Streptococcus Anginosus/Milleri Group (SAG) genomes reveals this to be a hot spot for genomic variability. A cluster of bacteriocin/immunity genes is found adjacent to the sil system in most SAG isolates (typically 6-10 per strain). In addition, there were two distinct SilCR peptides identified in this group, denoted here as SilCRSAG-A and SilCRSAG-B, with corresponding alleles in silB. Our analysis of the 42 sil loci showed that SilCRSAG-A is only found in Streptococcus intermedius while all three species can carry SilCRSAG-B. In S. intermedius B196, a putative SilA operator is located upstream of bacteriocin gene clusters, implicating the sil system in regulation of microbe-microbe interactions at mucosal surfaces where the group resides. We demonstrate that S. intermedius B196 responds to its cognate SilCRSAG-A, and, less effectively, to SilCRSAG-B released by other Anginosus group members, to produce putative bacteriocins and inhibit the growth of a sensitive strain of S. constellatus.

Calculated plasma volume status and prognosis in chronic heart failure.

AIMS: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients. METHODS AND RESULTS: First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2) = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort. CONCLUSIONS: Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation.

Saccharomyces cerevisiae and non-Saccharomyces yeasts in grape varieties of the São Francisco Valley.

The aims of this work was to characterise indigenous Saccharomyces cerevisiae strains in the naturally fermented juice of grape varieties Cabernet Sauvignon, Grenache, Tempranillo, Sauvignon Blanc and Verdejo used in the São Francisco River Valley, northeastern Brazil. In this study, 155 S. cerevisiae and 60 non-Saccharomyces yeasts were isolated and identified using physiological tests and sequencing of the D1/D2 domains of the large subunit of the rRNA gene. Among the non-Saccharomyces species, Rhodotorula mucilaginosa was the most common species, followed by Pichia kudriavzevii, Candida parapsilosis, Meyerozyma guilliermondii, Wickerhamomyces anomalus, Kloeckera apis, P. manshurica, C. orthopsilosis and C. zemplinina. The population counts of these yeasts ranged among 1.0 to 19 × 10(5) cfu/mL. A total of 155 isolates of S. cerevisiae were compared by mitochondrial DNA restriction analysis, and five molecular mitochondrial DNA restriction profiles were detected. Indigenous strains of S. cerevisiae isolated from grapes of the São Francisco Valley can be further tested as potential starters for wine production.

Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure.

BACKGROUND: An elevated red cell distribution width (RDW) and iron deficiency (ID) at baseline predict enhanced mortality in chronic heart failure (CHF), but little is known about the prognostic implications of their temporal trends. We sought to determine the survival implications of temporal changes in RDW and evolving ID in patients with CHF. METHODS: The relation between red cell indices on first consultation and over time with mortality in 274 stable patients with systolic CHF was analysed. The combination of a rising RDW with a falling mean cell volume (MCV) over time defined evolving ID. RESULTS: Over a median 12 month period, 51% and 23% of patients had a rise in RDW and evolving ID, respectively. After a median follow-up of 27 months, 60 (22%) patients died. A rising RDW predicted enhanced all-cause mortality (unadjusted HR for 1% per week rise 9.27, 95% CI 3.58 to 24.00, P<0.0001) independently and incrementally to baseline RDW, with an absolute increase >0.02% per week optimally predictive. Evolving ID also related to higher rates of mortality (HR 2.78, 95% CI 1.64 to 4.73, P<0.001) and was prognostically worse than a rising RDW alone (P<0.005). Patients with evolving ID who maintained their Hb levels over time had a 2-fold greater risk of death than those whose Hb levels declined without evolving ID. CONCLUSIONS: An expanding RDW and evolving iron deficiency over time predict an amplified risk of death in CHF and should be utilised for risk stratification and/or therapeutically targeted to potentially improve outcomes.