"Shepherd's crook" neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network.

The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity.

Zebrin II Expression in the Cerebellum of a Paleognathous Bird, the Chilean Tinamou (Nothoprocta perdicaria).

Zebrin II (ZII) is a glycolytic enzyme expressed in cerebellar Purkinje cells. In both mammals and birds, ZII is expressed heterogeneously, such that there are sagittal stripes of Purkinje cells with a high ZII expression (ZII+) alternating with stripes of Purkinje cells with little or no expression (ZII-). To date, ZII expression studies are limited to neognathous birds: pigeons (Columbiformes), chickens (Galliformes), and hummingbirds (Trochilidae). These previous studies divided the avian cerebellum into 5 transverse regions based on the pattern of ZII expression. In the lingular region (lobule I) all Purkinje cells are ZII+. In the anterior region (lobules II-V) there are 4 pairs of ZII+/- stripes. In the central region (lobules VI-VIII) all Purkinje cells are ZII+. In the posterior region (lobules VIII-IX) there are 5-7 pairs of ZII+/- stripes. Finally, in the nodular region (lobule X) all Purkinje cells are ZII+. As the pattern of ZII stripes is quite similar in these disparate species, it appears that it is highly conserved. However, it has yet to be studied in paleognathous birds, which split from the neognaths over 100 million years ago. To better understand the evolution of cerebellar compartmentation in birds, we examined ZII immunoreactivity in a paleognath, the Chilean tinamou (Nothoprocta perdicaria). In the tinamou, Purkinje cells expressed ZII heterogeneously such that there were sagittal ZII+ and ZII- stripes of Purkinje cells, and this pattern of expression was largely similar to that observed in neognathous birds. For example, all Purkinje cells in the lingular (lobule I) and nodular (lobule X) regions were ZII+, and there were 4 pairs of ZII+/- stripes in the anterior region (lobules II-V). In contrast to neognaths, however, ZII was expressed in lobules VI-VII as a series of sagittal stripes in the tinamou. Also unlike in neognaths, stripes were absent in lobule IXab, and all Purkinje cells expressed ZII in the tinamou. The differences in ZII expression between the tinamou and neognaths could reflect behavior, but the general similarity of the expression patterns across all bird species suggests that ZII stripes evolved early in the avian phylogenetic tree.

Electroablation: a method for neurectomy and localized tissue injury.

BACKGROUND: Tissue injury has been employed to study diverse biological processes such as regeneration and inflammation. In addition to physical or surgical based methods for tissue injury, current protocols for localized tissue damage include laser and two-photon wounding, which allow a high degree of accuracy, but are expensive and difficult to apply. In contrast, electrical injury is a simple and inexpensive technique, which allows reproducible and localized cell or tissue damage in a variety of contexts. RESULTS: We describe a novel technique that combines the advantages of zebrafish for in vivo visualization of cells with those of electrical injury methods in a simple and versatile protocol which allows the study of regeneration and inflammation. The source of the electrical pulse is a microelectrode that can be placed with precision adjacent to specific cells expressing fluorescent proteins. We demonstrate the use of this technique in zebrafish larvae by damaging different cell types and structures. Neurectomy can be carried out in peripheral nerves or in the spinal cord allowing the study of degeneration and regeneration of nerve fibers. We also apply this method for the ablation of single lateral line mechanosensory neuromasts, showing the utility of this approach as a tool for the study of organ regeneration. In addition, we show that electrical injury induces immune cell recruitment to damaged tissues, allowing in vivo studies of leukocyte dynamics during inflammation within a confined and localized injury. Finally, we show that it is possible to apply electroablation as a method of tissue injury and inflammation induction in adult fish. CONCLUSIONS: Electrical injury using a fine microelectrode can be used for axotomy of neurons, as a general tissue ablation tool and as a method to induce a powerful inflammatory response. We demonstrate its utility to studies in both larvae and in adult zebrafish but we expect that this technique can be readily applied to other organisms as well. We have called this method of electrical based tissue ablation, electroablation.

Extracellular recordings reveal absence of magneto sensitive units in the avian optic tectum.

There is a consensus that birds detect the earth's magnetic field and use some of its features for orientation and homing purposes. Since the late 1960s, when the first solid behavioral evidence of magnetoreception was obtained, much research has been devoted to describing the ethological aspects of this behavior. The neurophysiological basis of magnetoreception has been much less studied, although a frequently cited 1986 report described a high prevalence (70 %) of magneto-sensitive neurons in the pigeon optic tectum with high signal-to-noise ratios (Semm and Demaine, J Comp Physiol A 159:619-625, 1986). Here, we repeated these neurophysiological experiments using anesthetized as well as awake pigeons and new recording techniques. Our data indicate that magneto-sensitive units do not exist in the avian tectum.

Early Development of the Thalamo-Pallial Stage of the Tectofugal Visual Pathway in the Chicken (Gallus gallus).

The tectofugal pathway is a highly conserved visual pathway in all amniotes. In birds and mammals, retinorecipient neurons located in the midbrain roof (optic tectum/superior colliculus) are the source of ascending projections to thalamic relays (nucleus rotundus/caudal pulvinar), which in turn project to specific pallial regions (visual dorsal ventricular ridge [vDVR]/temporal cortex) organized according to a columnar recurrent arrangement of interlaminar circuits. Whether or to which extent these striking hodological correspondences arise from comparable developmental processes is at present an open question, mainly due to the scarcity of data about the ontogeny of the avian tectofugal system. Most of the previous developmental studies of this system in birds have focused on the establishment of the retino-tecto-thalamic connectivity, overlooking the development of the thalamo-pallial-intrapallial circuit. In this work, we studied the latter in chicken embryos by means of immunohistochemical assays and precise ex vivo crystalline injections of biocytin and DiI. We found that the layered organization of the vDVR as well as the system of homotopic reciprocal connections between vDVR layers were present as early as E8. A highly organized thalamo-vDVR projection was also present at this stage. Our immunohistochemical assays suggest that both systems of projections emerge simultaneously even earlier. Combined with previous findings, these results reveal that, in striking contrast with mammals, the peripheral and central stages of the avian tectofugal pathway develop along different timelines, with a tecto-thalamo-intrapallial organization arising before and possibly independently of the retino-isthmo-tectal circuit.

Urinary Cell Cycle Arrest Biomarkers and Diuretic Efficiency in Acute Heart Failure.

INTRODUCTION: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF). METHODS: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents. RESULTS: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score >0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively). CONCLUSION: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario.

Noncardiovascular morbidity and mortality across left ventricular ejection fraction categories following hospitalization for heart failure.

INTRODUCTION AND OBJECTIVES: Noncardiovascular events represent a significant proportion of the morbidity and mortality burden in patients with heart failure (HF). However, the risk of these events appears to differ by left ventricular ejection fraction (LVEF) status. In this study, we sought to evaluate the risk of noncardiovascular death and recurrent noncardiovascular readmission by LVEF status following an admission for acute HF. METHODS: We retrospectively assessed a cohort of 4595 patients discharged after acute HF in a multicenter registry. We evaluated LVEF as a continuum, stratified in 4 categories (LVEF ≤ 40%, 41%-49%, 50%-59%, and ≥ 60%). Study endpoints were the risks of noncardiovascular mortality and recurrent noncardiovascular admissions during follow-up. RESULTS: At a median follow-up of 2.2 [interquartile range, 0.76-4.8] years, we registered 646 noncardiovascular deaths and 4014 noncardiovascular readmissions. After multivariable adjustment including cardiovascular events as a competing event, LVEF status was associated with the risk of noncardiovascular mortality and recurrent noncardiovascular admissions. When compared with patients with LVEF ≤ 40%, those with LVEF 51%-59%, and especially those with LVEF ≥ 60%, were at higher risk of noncardiovascular mortality (HR, 1.31; 95%CI, 1.02-1,68; P=.032; and HR, 1.47; 95%CI, 1.15-1.86; P=.002; respectively), and at higher risk of recurrent noncardiovascular admissions (IRR, 1.17; 95%CI, 1.02-1.35; P=.024; and IRR, 1.26; 95%CI, 1.11-1.45; P=.001; respectively). CONCLUSIONS: Following an admission for HF, LVEF status was directly associated with the risk of noncardiovascular morbidity and mortality. Patients with HFpEF were at higher risk of noncardiovascular death and total noncardiovascular readmissions, especially those with LVEF ≥ 60%.

High-sensitivity C-reactive protein and risk of clinical outcomes in patients with acute heart failure.

Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF. We prospectively included a multicenter cohort of 3,395 patients following an admission for acute HF. HsCRP levels were evaluated during the first 24 h following admission. Study endpoints were the risks of all-cause mortality, CV-mortality, and total HF readmissions. The mean age was 74.2 ± 11.2 years and 1,826 (53.8%) showed a left ventricular ejection fraction (LVEF) ≥ 50%. Median hsCRP was 12.9 mg/L (5.4-30 mg/L). Over a median follow-up of 1.8 (0.6-4.1) years, 1,574 (46.4%) patients died, and 1,341 (39.5%) patients were readmitted for worsening HF. After multivariable adjustment, hsCRP values were significantly and positively associated with a higher risk of all-cause and CV mortality (p = 0.003 and p = 0.001, respectively), as well as a higher risk of recurrent HF admissions (p < 0.001). These results remained consistent across important subgroups, such as LVEF, sex, age, or renal function. In patients with acute HF, hsCRP levels were independently associated with an increased risk of long-term death and total HF readmissions.

CA125 outperforms NT-proBNP in the prediction of maximum aerobic capacity in heart failure with preserved ejection fraction and kidney dysfunction.

Background: Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. Methods: This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2). Results: The mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0-13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r = -0.43, P < .001 and r = -0.22, P = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [ß = 0.02 (95% confidence interval -0.19-0.23), P = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620). Conclusions: In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.

Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure.

BACKGROUND: There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure. OBJECTIVES: This study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes. METHODS: IRVF was assessed at baseline (pre-decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models. RESULTS: In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001). CONCLUSIONS: Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.

Attentional capture? Synchronized feedback signals from the isthmi boost retinal signals to higher visual areas.

When a salient object in the visual field captures attention, the neural representation of that object is enhanced at the expense of competing stimuli. How neural activity evoked by a salient stimulus evolves to take precedence over the neural activity evoked by other stimuli is a matter of intensive investigation. Here, we describe in pigeons (Columba livia) how retinal inputs to the optic tectum (TeO, superior colliculus in mammals), triggered by moving stimuli, are selectively relayed on to the rotundus (Rt, caudal pulvinar) in the thalamus, and to its pallial target, the entopallium (E, extrastriate cortex). We show that two satellite nuclei of the TeO, the nucleus isthmi parvocelullaris (Ipc) and isthmi semilunaris (SLu), send synchronized feedback signals across tectal layers. Preventing the feedback from Ipc but not from SLu to a tectal location suppresses visual responses to moving stimuli from the corresponding region of visual space in all Rt subdivisions. In addition, the bursting feedback from the Ipc imprints a bursting rhythm on the visual signals, such that the visual responses of the Rt and the E acquire a bursting modulation significantly synchronized to the feedback from Ipc. As the Ipc feedback signals are selected by competitive interactions, the visual responses within the receptive fields in the Rt tend to synchronize with the tectal location receiving the "winning" feedback from Ipc. We propose that this selective transmission of afferent activity combined with the cross-regional synchronization of the areas involved represents a bottom-up mechanism by which salient stimuli capture attention.

A blinking focal pattern of re-entrant activity in the avian tectum.

Re-entrant connections are inherent to nervous system organization; however, a comprehensive understanding of their operation is still lacking. In birds, topographically organized re-entrant signals, carried by axons from the nucleus-isthmi-parvocellularis (Ipc), are distinctly recorded as bursting discharges across the optic tectum (TeO). Here, we used up to 48 microelectrodes regularly spaced on the superficial tectal layers of anesthetized pigeons to characterize the spatial-temporal pattern of this axonal re-entrant activity in response to different visual stimulation. We found that a brief luminous spot triggered repetitive waves of bursting discharges that, appearing from initial sources, propagated horizontally to areas representing up to 28° of visual space, widely exceeding the area activated by the retinal fibers. In response to visual motion, successive burst waves started along and around the stimulated tectal path, tracking the stimulus in discontinuous steps. When two stimuli were presented, the burst-wave sources alternated between the activated tectal loci, as if only one source could be active at any given time. Because these re-entrant signals boost the retinal input to higher visual areas, their peculiar dynamics mimic a blinking "spotlight," similar to the internal searching mechanism classically used to explain spatial attention. Tectal re-entry from Ipc is thus highly structured and intrinsically discontinuous, and higher tectofugal areas, which lack retinotopic organization, will thus receive incoming visual activity in a sequential and piecemeal fashion. We anticipate that analogous re-entrant patterns, perhaps hidden in less bi-dimensionally organized topographies, may organize the flow of neural activity in other parts of the brain as well.

Biomarkers to Improve Decision-making in Acute Heart Failure.

Acute heart failure (AHF) is a complex clinical syndrome that requires prompt diagnosis, risk stratification and effective treatment strategies to reduce morbidity and mortality. Biomarkers are playing an increasingly important role in this process, offering valuable insights into the underlying pathophysiology and facilitating personalised patient management. This review summarises the significance of various biomarkers in the context of AHF, with a focus on their clinical applications to stratify risk and potential for guiding therapy choices.

An update on utilising brain natriuretic peptide for risk stratification, monitoring and guiding therapy in heart failure.

INTRODUCTION: Heart failure (HF) is a dominant health problem with an overall poor prognosis. Natriuretic peptides (NPs) are upregulated in HF as a compensatory mechanism. They have been extensively used for diagnosis and risk stratification. AREAS COVERED: This review addresses the history and physiology of NPs in order to understand their current role in clinical practice. It further provides a detailed and updated narrative review on the utility of those biomarkers for risk stratification, monitoring, and guiding therapy in HF. EXPERT OPINION: NPs show excellent predictive ability in heart failure patients, both in acute and chronic settings. Understanding their pathophysiology and their modifications in specific situations is key for an adequate interpretation in specific clinical scenarios in which their prognostic value may be weaker or less well evaluated. To better promote risk stratification in HF, NPs should be integrated with other predictive tools to develop multiparametric risk models. Both inequalities of access to NPs and evidence caveats and limitations will need to be addressed by future research in the coming years.

Change in the neurochemical signature and morphological development of the parvocellular isthmic projection to the avian tectum.

Neurons can change their classical neurotransmitters during ontogeny, sometimes going through stages of dual release. Here, we explored the development of the neurotransmitter identity of neurons of the avian nucleus isthmi parvocellularis (Ipc), whose axon terminals are retinotopically arranged in the optic tectum (TeO) and exert a focal gating effect upon the ascending transmission of retinal inputs. Although cholinergic and glutamatergic markers are both found in Ipc neurons and terminals of adult pigeons and chicks, the mRNA expression of the vesicular acetylcholine transporter, VAChT, is weak or absent. To explore how the Ipc neurotransmitter identity is established during ontogeny, we analyzed the expression of mRNAs coding for cholinergic (ChAT, VAChT, and CHT) and glutamatergic (VGluT2 and VGluT3) markers in chick embryos at different developmental stages. We found that between E12 and E18, Ipc neurons expressed all cholinergic mRNAs and also VGluT2 mRNA; however, from E16 through posthatch stages, VAChT mRNA expression was specifically diminished. Our ex vivo deposits of tracer crystals and intracellular filling experiments revealed that Ipc axons exhibit a mature paintbrush morphology late in development, experiencing marked morphological transformations during the period of presumptive dual vesicular transmitter release. Additionally, although ChAT protein immunoassays increasingly label the growing Ipc axon, this labeling was consistently restricted to sparse portions of the terminal branches. Combined, these results suggest that the synthesis of glutamate and acetylcholine, and their vesicular release, is complexly linked to the developmental processes of branching, growing and remodeling of these unique axons.

Applicability of Echocardiographic Strict Negative Criteria for Suspected Infective Endocarditis.

Echocardiography is the cornerstone imaging technique in the diagnosis of infective endocarditis (IE) but is often misused in clinical practice. Recently, strict negative criteria have been proposed to avoid unnecessary follow-up echocardiograms. We aimed to evaluate the use of echocardiography in real-world clinical daily practice and the usefulness of these criteria in the diagnosis of IE. We retrospectively retrieved every echocardiogram performed in our center for suspected IE between 2014 and 2018, including 905 transthoracic echocardiograms (TTEs). Of these, 451 (49.8%) fulfilled the strict negative criteria (group 1). In this group, IE was seldom diagnosed (n = 4, 0.9%). In 338 patients (37.4%) no signs of IE were evident, but they did not fulfill the strict negative criteria (group 2). A follow-up echocardiogram and definitive diagnosis of IE were more frequent (n = 48, 14.2% and n = 20, 5.9%). Finally, in 116 patients (12.8%) the initial TTE showed typical or suggestive signs of IE, in whom the diagnosis was confirmed in 48 patients (41.4%). A definitive diagnosis of IE was established in a minority of the study population (n = 72, 8%). Only 1 readmission for underdiagnosis of IE was noted on group 2. We conclude that in a real-life setting only a minority of patients in whom IE was suspected had a definitive diagnosis. An initial TTE for suspected IE fulfilling the strict negative criteria predicts both a low probability of requesting a follow-up study and of a definitive diagnosis of IE.

Sex-Related Differences in Mortality Following Admission for Acute Heart Failure Across the Left Ventricular Ejection Fraction Spectrum.

Background Following a heart failure (HF)-decompensation, there is scarce data about sex-related prognostic differences across left ventricular ejection fraction (LVEF) status. We sought to evaluate sex-related differences in 6-month mortality risk across LVEF following admission for acute HF. Methods and Results We retrospectively evaluated 4812 patients consecutively admitted for acute HF in a multicenter registry from 3 hospitals. Study end points were all-cause, cardiovascular, and HF-related mortality at 6-month follow-up. Multivariable Cox regression models were fitted to investigate sex-related differences across LVEF. A total of 2243 (46.6%) patients were women, 2569 (53.4%) were men, and 2608 (54.2%) showed LVEF≥50%. At 6-month follow-up, 645 patients died (13.4%), being 544 (11.3%) and 416 (8.6%) cardiovascular and HF-related deaths, respectively. LVEF was not independently associated with mortality (HR, 1.02; 95% CI 0.99-1.05; P=0.135). After multivariable adjustment, we found no sex-related differences in all-cause mortality (P value for interaction=0.168). However, a significant interaction between sex and cardiovascular and HF mortality risks was found across LVEF (P value for interaction=0.030 and 0.007, respectively). Compared with men, women had a significantly lower risk of cardiovascular and HF-mortality at LVEF<25% and <43%, respectively. On the contrary, women showed a higher risk of HF-mortality at the upper extreme of LVEF (>80%). Conclusions Following an admission for acute HF, no sex-related differences were found in all-cause mortality risk. However, when compared with men, women showed a lower risk of cardiovascular and HF-mortality at the lower extreme of LVEF. On the contrary, they showed a higher risk of HF death at the upper extreme.

Exercise ECG Testing and Stress Cardiac Magnetic Resonance for Risk Prediction in Patients With Chronic Coronary Syndrome.

PURPOSE: Vasodilator stress cardiac magnetic resonance (VS-CMR) has become crucial in the workup of patients with known or suspected chronic coronary syndrome (CCS). Whether traditional exercise ECG testing (ExECG) contributes prognostic information beyond VS-CMR is unclear. METHODS: We retrospectively included 288 patients with known or suspected CCS who had undergone ExECG and subsequent VS-CMR in our institution. Clinical, ExECG, and VS-CMR variables were recorded. We defined the serious adverse events (SAE) as a combined endpoint of acute coronary syndrome, admission for heart failure, or all-cause death. RESULTS: During a mean follow-up of 4.2 ± 2.15 yr, we registered 27 SAE (15 admissions for acute coronary syndrome, eight admissions for heart failure, and four all-cause deaths). Once adjusted for clinical, ExECG, and VS-CMR parameters associated with SAE, the only independent predictors were HRmax in ExECG (HR = 0.98: 95% CI, 0.96-0.99; P = .01) and more extensive stress-induced perfusion defects (PDs, number of segments) in VS-CMR (HR = 1.19: 95% CI, 1.07-1.34; P < .01). Adding HRmax significantly improved the predictive power of the multivariable model for SAE, including PDs (continuous reclassification improvement index: 0.47: 95% CI, 0.10-0.81; P < .05). The annualized SAE rate was 1% (if PD < 2 segments and HRmax > 130 bpm), 2% (if PD < 2 segments and HRmax ≤ 130 bpm), 3.2% (if PD ≥ 2 segments and HRmax > 130 bpm), and 6.3% (if PD ≥ 2 segments and HRmax ≤ 130 bpm), P < .01, for the trend. In patients on ß-blocker therapy, however, only PDs in VS-CMR, but not HRmax, predicted SAE. CONCLUSIONS: We conclude that ExECG contributes significantly to prognostic information beyond VS-CMR in patients with known or suspected CCS.

CA125 but not NT-proBNP predicts the presence of a congestive intrarenal venous flow in patients with acute heart failure.

BACKGROUND: Intrarenal venous flow (IRVF) measured by Doppler ultrasound has gained interest as a potential surrogate marker of renal congestion and adverse outcomes in heart failure. In this work, we aimed to determine if antigen carbohydrate 125 (CA125) and plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with congestive IRVF patterns (i.e., biphasic and monophasic) in acute heart failure (AHF). METHODS AND RESULTS: We prospectively enrolled a consecutive cohort of 70 patients hospitalized for AHF. Renal Doppler ultrasound was assessed within the first 24-h of hospital admission. The mean age of the sample was 73.5 ± 12.3 years; 47.1% were female, and 42.9% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for NT-proBNP and CA125 were 6149 (3604-12 330) pg/mL and 64 (37-122) U/mL, respectively. The diagnostic performance of both exposures for identifying congestive IRVF patterns was tested using the receiving operating curve (ROC). The cut-off for CA125 of 63.5 U/mL showed a sensibility and specificity of 67% and 74% and an area under the ROC curve of 0.71. After multivariate adjustment, CA125 remained non-linearly and positively associated with congestive IRVF (P-value = 0.008) and emerged as the most important covariate explaining the variability of the model (R2: 47.5%). Under the same multivariate setting, NT-proBNP did not show to be associated with congestive IRVF patterns (P-value = 0.847). CONCLUSIONS: CA125 and not NT-proBNP is a useful marker for identifying patients with AHF and congestive IRVF patterns.

Intratelencephalic projections of the avian visual dorsal ventricular ridge: Laminarly segregated, reciprocally and topographically organized.

Recent reports have shown that the avian visual dorsal ventricular ridge (DVR) is organized as a trilayered complex, in which the forming layers-the thalamo-recipient entopallium (E), an overlaying nidopallial stripe called intermediate nidopallium (NI), and the dorsally adjacent mesopallium ventrale-appear to be extensively interconnected by topographically organized columns of reciprocal axonal processes running perpendicular to the layers, an arrangement highly reminiscent to that of the sensory cortices of mammals. In the present report, we implemented in vivo anterograde and retrograde tracing techniques aiming to elucidate the organization of the connections of this complex with other pallial areas. Previous studies have shown that the efferent projections of the visual DVR originate mainly from the NI and E, reaching several distinct associative and premotor nidopallial areas. We found that the efferents from the visual DVR originated solely from the NI, and confirmed that the targets of these projections were the pallial areas described by previous studies. We also found novel projections from the NI to the visual hyperpallium, and to the lateral striatum. Moreover, we found that these projections were reciprocal, topographically organized, and originated from different cell populations within the NI. We conclude that the NI constitutes a specialized layer of the visual DVR that form the core of a dense network of highly specific connections between this region and other higher order areas of the avian pallium. Finally, we discuss to what extent these hodological properties resemble those of the mammalian cortical layers II/III.