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Background: Affective neuroscience (AN) theory assumes the existence of seven basic emotional systems (i.e., SEEKING, ANGER, FEAR, CARE, LUST, SADNESS, PLAY) that are common to all mammals and evolutionarily determined to be tools for survival and, in general, for fitness. Based on the AN approach, the Affective Neuroscience Personality Scales (ANPS) questionnaire was developed to examine individual differences in the defined basic emotional systems. The current systematic review aims to examine the use of ANPS in clinical contexts attempting to define those behavioral elements associated with underlying stable personality traits., Methods: The systematic review was conducted following the PRISMA statements. PubMed and PsycInfo were used for research literature from March 2003 to November 2021., Results: Forty-four studies including ANPS were identified from 1763 studies reviewed. Sixteen studies met the inclusion criteria., Limitations: The review comprised some papers with incomplete psychological assessments (e.g., lack of other measures in addition to the ANPS) and missing information (e.g., on the [sub]samples), which may affect the generalizability of findings., Conclusion: Specific endophenotypes and/or patterns of emotional/motivational systems were found for several mental disorders. Specifically, endophenotypes emerged for the Depressive and Autism Spectrum Disorders, Borderline and Avoidant Personality Disorders, type I and II Bipolar Disorders, and the Obsessive-Compulsive Disorder. The endophenotypes can provide useful reflective elements for both psychodiagnosis and intervention. Overall, the current study may represent an attempt to contribute to the understanding of the basic emotional systems involved in the psychopathological manifestations identified by AN., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Emotion regulation (ER) is a core element for individual well-being, and dysregulated emotional states are prominent in several mental disorders. Moreover, dispositional use of adaptive ER strategies, such as cognitive reappraisal, is usually associated to better psychological outcomes and less emotional problems. Thus, identifying markers of emotion dysregulation could serve as a key point for developing treatments against risks of psychopathological outcomes. Neuroimaging techniques could represent a useful tool within these aims, focusing on neurobiological markers of psychopathological illness. Given the well known gender differences in using ER strategies, we examined behavioral and neuroimaging patterns associated with dispositional use of reappraisal among a non-clinical female sample. We found that the individual predisposition to use cognitive reappraisal as an emotion regulation strategy was associated with decreased levels of dysregulation. From a neurobiological perspective, difficulties in using reappraisal were associated with decreased resting-state functional connectivity (rs-FC) between the Middle Temporal Gyrus and occipito-parietal regions. Moreover, rs-FC between prefrontal and occipito-parietal brain regions was negatively associated with emotion dysregulation levels. Microstructural anomalies across white matter tracts connecting temporal, parietal, and occipital brain regions were associated to difficulties in using reappraisal. Our findings suggest that specific behavioral and neurobiological substrates are linked to reappraising abilities. Furthermore, the ability to implement adaptive ER strategies could serve as protective factor against developing emotion dysregulation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although larger trinucleotide expansions give rise to a neurodevelopmental disorder called fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a "premutation" (55-200 CGG repeats) in the FMR1 gene. FXTAS is one of the more common single-gene forms of late-onset ataxia and tremor that may have a more complex development in women, with atypical presentations. After a brief presentation of the atypical case of an Italian woman with FXTAS, who had several paroxysmal episodes suggestive of acute cerebellar and/or brainstem dysfunction, this article will revise the phenotype of FXTAS in women. Especially in females, FXTAS has a broad spectrum of symptoms, ranging from relatively severe diseases in mid-adulthood to mild cases beginning in later life. Female FXTAS and male FXTAS have a different symptomatic spectrum, and studies on the fragile X premutation should be conducted separately on women or men. Hopefully, a better understanding of the molecular processes involved in the polymorphic features of FXTAS will lead to more specific and effective therapies for this complex disorder.

Recently, an eye-tracking study found that Complexity and other R-PAS variables located in the Engagement and Cognitive Processing domain correlated with a proxy marker for cognitive effort and engagement. The goal of the current study was to test the robustness and validity of those eye-tracking findings by inspecting fMRI data. We hypothesized that the greater the level of engagement and cognitive effort put in place by a Rorschach test-taker, the greater the engagement of his/her cortical areas reflecting ongoing top-down attentional processes should be. We re-analyzed archival fMRI data from 26 healthy participants exposed to the Rorschach inkblots with the instruction to think of what they might be. The association of various Engagement and Cognitive Processing R-PAS scores to increased BOLD signals in the Dorsal Attention Network of the brain was examined. As expected, Complexity showed the strongest effect size across all R-PAS variables under investigation ( d  = 0.43), followed by Synthesis ( d  = 0.32) and Human Movement ( d  = 0.21). Noteworthy, the correlation between the effect sizes found in the current fMRI study and those found in the previously published eye-tracking study consists of an impressive r = .80.

We introduce the concept of "neurobiological foundation" of Rorschach interpretations as an extension of the concept of behavioral representation as a foundation for interpretation of R-PAS variables. Here, we propose that if there is a parallelism between the mental, verbal and perceptual behaviors occurring within the microcosm of the Rorschach task and those occurring in the external environment [behavioral foundation], then the same brain regions engaged by the test-taker when producing of a given code, should be engaged also when reproducing, in the external environment, the same psychological processes underlying that specific Rorschach code [neurobiological foundation]. To investigate this concept, we used archival, fMRI data and tested whether producing Oral Dependency Language (ODL) responses would associate with increased activation in brain regions associated with dependency-related, psychological processes. Results from a sample of 21 non-clinical volunteers partially confirmed our hypothesis, providing some support to the neurobiological foundation of the ODL code., (© 2019 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Introduction: The P2X7 receptor-NLRP3 inflammasome complex (P2X7R-Infl) regulates inflammatory and immune responses. Physical exercise modulates heat-shock proteins (Hsps), influencing cytokine levels and oxidative stress; Hsp72 triggers P2X7R-Infl-dependent responses., Subjects and Methods: We studied the effect of a single bout of maximal exercise on lymphomonocyte expression of P2X7R, NLRP3, caspase-1, NF-kB and Hsp72 and circulating levels of IL-1β, IL-18 and MCP-1, all modulated by P2X7R-Infl, in healthy sedentary (SED), trained (ATH), endurance (END) male individuals., Results: Baseline P2X7R, NLRP3 and Caspase-1 expression progressively increased from SED to ATH and END; NF-kβ showed the same trend. Hsp72 did not differ among groups. Acute exercise strongly reduced P2X7R in all participants, irrespective of their degree of physical training. Inflammasome responses differed across groups: in SED, NLRP3 and Caspase-1 increased; in ATH, NLRP3 reduced and caspase-1 did not vary; in END, NLRP3 and Caspase-1 declined. Baseline IL-1β, higher in END, was unmodified after exercise; IL-18 decreased; MCP-1 doubled in SED, did not vary in ATH, declined in END. In the whole study population, significant direct relationships emerged between P2X7R expression and IL-1β, IL-18, MCP-1 levels, all P < .001; also Caspase-1 related with these markers. A multivariate analysis showed age, BMI and P2X7R as determinants of postexercise IL-1β levels., Conclusion: Endurance show higher P2X7R-Infl expression and function vs SED and ATH; however, maximal exercise determines prevailing pro-inflammatory vs anti-inflammatory responses in untrained and trained participants, respectively, highlighting a likely cause-effect relationship between degree of physical activity and P2X7R-Infl-mediated responses., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms., Methods: Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used., Results: Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals., Conclusions: An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction.

Heart failure (HF) is one of the most frequent cause of hospitalization in elderly and often coexists with concurrent geriatric syndromes, like cognitive disturbances; various pathophysiological mechanisms are shared by HF and cognitive decline, notably a substrate of low-grade inflammation. We investigated whether SNPs in the purinergic receptor (P2X 7 R) and apolipoprotein (APO) E genes, both involved in a series of inflammatory responses, are associated to HF or cognitive impairment and are able to predict post-discharge mortality in the elderly. We prospectively analyzed 198 patients (age 85 ± 8 years, predominantly females) admitted to a Geriatric unit for acute HF, whose diagnosis was based on clinical signs, brain natriuretic peptide (BNP) values and ecocardiography in uncertain diagnosis (BNP values between 100 and 400 pg/mL); cognitive performance was assesed by Short Portable Mental Status Questionnaire (SPMSQ). In all the participants, SNPs rs208294 and rs3751143 for P2X 7 R gene and rs429558 and rs7412 for APOE gene were assessed. Information on all-cause mortality was adjudicated by medical records review 36 months after discharge. We found no relationship between P2X 7 R and APOE polymorphisms and 36-month post-discharge mortality; a better outcome for overall survival was observed in patients with BNP values below the median (281 pg/mL) ( p =0.002) persisting after adjustment for renal function and age, and in those with cognitive impairment ( p <0.001). Patients harboring APOE-ε4 genotype showed higher BNP concentrations than noncarriers (1289.9 ± 226.9 vs 580.5 ± 90.2 pg/mL respectively, p =0.004), whereas none of the studied SNPs were associated to impairment in cognitive performance. In conclusion, neither P2X 7 R or APOE genotype seem to predict long-term mortality in elderly patients. Interestingly, APOE-ε4 genotype was associated to higher BNP values, suggesting a putative interaction between genetic and biochemical markers in identifying people at risk for HF., Competing Interests: Conflict of Interest The Authors have nothing to disclose

Aims: Obesity-induced nephropathy is an established clinical entity arising from a "maladaptive" response to lipid accumulation at the nephron level. Bariatric surgery positively affects renal function, reducing or increasing glomerular filtration rate (GFR) in subjects with hyperfiltration and renal impairment, respectively. The effect of this surgery in patients with normal estimated GFR (eGFR) is less clear., Methods: A complete clinical and biochemical assessment of 135 severely obese, otherwise healthy subjects, was obtained before Roux-en-Y gastric bypass (RYGB). All subjects underwent an OGTT with plasma glucose and insulin determinations. Follow-up data were recorded at 6, 12, 24 and 48 months after intervention., Results: Baseline eGFR was 98.2 ± 13.6 ml/min/1.73 m 2 ; hyperfiltration (>120 ml/min/1.73 m 2 ) was present in 7% of the cohort. No eGFR variation over the follow-up emerged, except at the last visit (-3.6 ± 1.4 ml/min/1.73 m 2 at month 48, p = 0.01 vs baseline). In the univariate analysis, the renal performance at 48 months was inversely related to baseline eGFR (r = -0.17, p = 0.04) and plasma triglycerides (r = -0.04, p = 0.05). Fasting and OGTT-derived variables did not impact eGFR. By multiple regression analysis, eGFR time course was independently predicted only by baseline eGFR (p = 0.03). Interestingly, patients having a baseline eGFR >100 ml/min/1.73 m 2 (median value) showed, after 48 months, an average loss of -8.3 ± 2.2 ml/min/1.73 m 2 , while those with eGFR <100 exhibited a slight increase (+1.8 ± 2.3 ml/min/1.73 m 2 , p < 0.01)., Conclusions: Long-term data confirm the safety of RYGB on renal function. Interestingly, a subtle hyperfiltration, i.e., occurring in high-normal range of eGFR, is attenuated by surgical procedure. Lastly, high serum triglycerides may track an unfavorable renal outcome.

Aims: The cost-effectiveness of screening for silent coronary heart disease (CHD) in type 2 diabetes (DM2) is still debated., Methods: We applied a diagnostic algorithm for silent CHD detection, in a cohort of 102 asymptomatic DM2 subjects (57±7years), attending 5 Italian outpatient clinics, to verify its predictive value. The risk of silent CHD was calculated considering classical risk factors, and presence of microangiopathy/macroangiopathy. Patients were divided in 3 groups, i.e. group 1: normal ECG and low silent CHD risk; group 2: abnormal ECG, irrespective of silent CHD risk; group 3: high silent CHD risk, irrespective of ECG. To group 2 and 3, a functional test was recommended and performed in 78% of patients., Results: Silent CHD prevalence was similar in group 2 and 3 (25 vs. 17% respectively; p=0.495). However, evaluating the entire cohort, a significant higher prevalence of silent CHD was observed in subjects with abnormal vs. normal ECG (23 vs. 4%; P=0.004), but not in subjects with high vs. low pre-test silent CHD risk (14 vs. 9%; p=0.472)., Conclusions: An abnormal ECG was a strong, independent predictor of silent CHD (OR 8.9; CI 1.27-62.5; p=0.028) in DM2. Therefore, a functional stress testing should be considered in DM2 patients with ECG abnormalities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Several patients encompass a scarce weight loss after Roux-en-Y gastric bypass (RYGB). As such event is not related to surgical complications, finding markers able to identify "well responders" and to predict weight loss outcome is clinically relevant. Ghrelin regulates appetite and energy balance. Common single nucleotide polymorphisms (SNPs) in its encoding genes have been associated with body weight regulation. Other peptides involved in satiety modulation, like the CD40/CD40L complex, are less explored., Methods: One hundred, otherwise healthy, obese subjects (aged 45 ± 11 years, 65 females, BMI 48.0 ± 0.7 kg/m 2 ) were sequentially enrolled in years 2014-2015. SNPs rs2241766 for adiponectin gene, rs490683 for ghrelin receptor, rs696217 and rs27647 for the preproghrelin/ghrelin gene, and rs1126535 for the CD40L gene were determined on DNA extracted from circulating lymphomonocytes. Patients were reevaluated at 6 (n = 100), 26 (n = 91), and 52 weeks (n = 79) after RYGB., Results: Subjects carrying the rs696217 T allele encompassed a significantly greater reduction in BMI 52 weeks after surgery (GG vs GT 30.5 ± 1.1 vs 38.1 ± 2.1 %; p < 0.001). Carrying the rs1126535 C allele in the CD40L gene was associated with a significantly lower BMI reduction at week 52 (TT vs CT 33.2 ± 1.1 vs 28.1 ± 2.3 %, p = 0.049). rs490683 and rs27647 SNPs of ghrelin and rs2241766 for adiponectin gene did not show any difference between carriers and non-carriers of the mutant allele., Conclusion: Carrying a G to T substitution in rs696217 (preproghrelin gene) seems to mark a successful weight loss outcome; we also report for the first time that the rs1126535 C allele (CD40L gene) may predict a worse response to bariatric surgery.

Public, nonprofit and private organisations respond to large-scale disasters domestically and overseas. Critics of these assistance efforts, as well as those involved, often cite poor interorganisational partnering as an obstacle to successful disaster response. Observers frequently call for 'more' and 'better' partnering. We found important qualitative distinctions existed within partnering behaviours. We identified four different types of interorganisational partnering activities often referred to interchangeably: communication, cooperation, coordination and collaboration-the Four Cs. We derived definitions of the Four Cs from the partnering literature. We then tested them in a case study of the response to the 2010 Haiti earthquake. We suggest that the Four Cs are distinct activities, that organisations are typically strong or weak in one or more for various reasons, and that the four terms represent a continuum of increased interorganisational embeddedness in partnering activities., (© 2016 The Author(s). Disasters © Overseas Development Institute, 2016.)

Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR) is unusual, and how estimation formulae (EstForm) perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm., Methods: We measured GFR (mGFR) by iohexol plasma clearance, renal plasma flow (RPF) by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD) as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects., Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis). mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67), accounting for 15% and 21% of mGFR variance, respectively., Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR., (© 2016 The Author(s) Published by S. Karger GmbH, Freiburg.)

Objective: Smoking is a recognized cardiovascular risk factor. Perivascular visceral adipose tissue (PVAT) is a source of inflammatory molecules, thus contributing to atherosclerosis progression. The P2X7 receptor (P2X7 R)-inflammasome complex, crucial in determining IL-1β and IL-18 release, participates in this scenario. We evaluated whether smoking might affect the PVAT inflammatory phenotype and explored the putative role of the axis P2X7 R-inflammasome in this picture., Subjects and Methods: TNFα, IL-6, RBP4, MCP-1, as well as P2X7 R and inflammasome components NLRP3, ASC, caspase-1 and IL-1β and IL-18 expression was determined in adipocytes isolated by PVAT of healthy smokers (Smok) and nonsmokers (No-Smok) subjects. Plasma and culture medium levels of these cytokines were also determined., Results: Perivascular adipose tissue of Smok had a higher expression of P2X7 R and inflammasome components; via P2X7 R activation, it released more IL-1β and IL-18, whose serum levels were also higher in Smok than in No-Smok. Linear correlations of NLRP3 with P2X7 R and IL-18 expression and release emerged. Smok also had a higher PVAT expression of the chemotactic factor MCP-1. However, no difference was observed in the PVAT expression of genes more strictly related to insulin resistance, like TNFα, RBP4, IL-6; this was coupled with similar plasma levels of TNFα and RBP4 in the two groups., Conclusion: Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation.)

The aim of this study was to evaluate the effects of preload reduction on the Doppler transmitral flow pattern in the presence of diastolic dysfunction (hypertensive patients) and normal diastolic function (normal subjects) to identify, if present, one or more indexes of abnormal diastolic ventricular filling independent of variations in preload. For this purpose Doppler echocardiography was performed in 17 patients with hypertension and in 18 normal subjects under basal conditions and after 5 minutes of blood pressure cuff inflation at the root of the four limbs. The two groups showed a similar response to preload reduction: a significant reduction in peak velocity and the time-velocity integral of the E wave and in the ratio of peak velocities of E and A waves. Therefore the differences in left ventricular filling patterns between hypertensive and normal subjects observed under basal conditions were still present after preload reduction. The comparison between normal subjects after preload reduction and hypertensive patients in the basal state showed a higher peak velocity and time-velocity integral of the A wave in the latter (61.2 +/- 16.2 vs 46.2 +/- 9 cm/sec [p less than 0.002] and 5.4 +/- 1.8 vs 3.7 +/- 1 cm [p less than 0.002], respectively) with no differences in the ratios of peak velocities and time-velocity integrals of the E and A waves.(ABSTRACT TRUNCATED AT 250 WORDS)

The normal values of the systolic time intervals (STI) in children and their possible relationship with heart rate have not been studied thoroughly. From a group of 9760 healthy school-children 10-12 years old, 488 subjects of both sexes were randomly selected in order to measure the STI and calculate the respective indices. The final population study was composed of 479 children, 249 males and 230 females, aged from 10/1 to 12/2 years/months (mean age 11/1 +/- 0/4 years/months). In each child, the following STI were measured: total electromechanical systole (Q-S2), left ventricular ejection time (LVET), mechanical systole (S1-S2), preejection period (PEP), PEP/LVET ratio and isovolumic contraction time (ICT). For each parameter, the regression equation with heart rate was calculated using a linear model and was verified if a real difference existed between linear regressions of males and females. Moreover, for each parameter, the index from the respective regression equation was calculated as well as its normal value and the standard deviation. Finally, the diastolic time (% diastole) and its correlation with heart rate were calculated. Our results demonstrate that in children, a close correlation exists between the STI and heart rate, although less striking than in adults; only the PEP/LVET ratio appears independent from heart rate, as in adults. The % diastole versus heart rate non-linear relationship shows the same behaviour as in adults. Finally, in agreement with other authors, our results show that in childhood the relationship between the STI and heart rate behaves alike in males and females.

In the last few years, alterations in transmitral diastolic flow pattern have been used to assess changes in left ventricular diastolic properties. However, since diastolic flow primarily reflects the atrioventricular pressure gradient, loading conditions, as well as intrinsic left ventricular properties, should be able to affect this pattern. This study was selectively designed to decrease preload (a major determinant of the atrioventricular pressure gradient) in normal subjects to observe the effects on the Doppler transmitral flow pattern without pharmacologic interventions that may also affect left ventricular diastolic properties. In 12 normal subjects, preload was reduced by inflation of blood pressure cuffs placed at the level of the root of the 4 limbs. The peak velocity of early mitral flow (E wave) decreased from 62 +/- 8 to 51 +/- 7 cm/s (p less than 0.001), while no changes were found in the maximal velocity after atrial contraction; this caused a significant decrease in the ratio of these 2 velocities (the E to A ratio) from 1.5 +/- 0.3 to 1.1 +/- 0.1 (p less than 0.001). The time-velocity integral of early diastolic inflow decreased from 7.8 +/- 1.3 to 6.1 +/- 1.3 cm (p less than 0.001) with no significant changes of the time-velocity integral of inflow after atrial contraction. Therefore, preload reduction in normal subjects significantly reduces transmitral flow in early diastole with preserved late ventricular filling, producing a pattern that can mimic the changes previously described in left ventricular diastolic dysfunction.