Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning

Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n= 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n= 9; spironolactone, 100 mg day-1 for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P \u3c 0.05). Head-down bed rest with hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P \u3c 0.05), and this was associated with bed-rest-induced development of the following changes: (i) enhanced activation within the genual anterior cingulate cortex and the right anterior insular cortex; and (ii) deactivation patterns within the subgenual regions of the anterior cingulate cortex. Diuretic treatment (without HDBR) did not affect baseline HR and mean arterial pressure, but did reduce resting HRV and elevated circulating noradrenaline and plasma renin activity (P \u3c 0.05). The greater HR response to LBNP following diuretic (P \u3c 0.05) was associated with diminished activation of the right anterior insula. Our findings indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline autonomic and cardiovascular variables. The findings also indicate that despite the similar augmentation of HR responses to LBNP and despite similar pre-intervention cortical activation patterns, HDBR and diuretic treatment produced different effects on the cortical responses, with HDBR affecting anterior cingulate cortex and right insula regions, whereas diuretic treatment affected primarily the right insula alone, but in a direction that was opposite to HDBR. The data indicate that physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control. © 2012 The Physiological Society

What Therapists Learn from Psychotherapy Clients: Effects on Personal and Professional Lives

While considerable research has examined how clients learn from psychotherapists, there is only sparse literature on what therapists learn from their therapy clients. In a qualitative, exploratory study, nine researchers interviewed 61 psychologists from across North America in order to see what psychotherapists may have learned and how they have been affected by their clients both personally and professionally. Participants responded to nine open-ended questions on learning about life-lessons, relationships, ethical decision-making, coping, courage, wisdom, psychopathology, personality, cultural differences, lifespan development and more. Participants’ richly elaborated responses were coded thematically and narrative data illustrates the most frequent themes. Therapists reported learning a great deal across each of the questions, consistently expressing respect for their clients\u27 resilience, courage and moral sensibilities

Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI

With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher r(1) relaxivity at low fields, but tend to lose this merit when used as T-1 contrast agents (r(1)/r(2) = 0.5 similar to 1), with their r(1) decreasing and r(2) increasing as magnetic field strength increases. Here, we developed and characterized an in vivo applicable magnetic resonance (MR) positive contrast agent by conjugating Gd(III)-chelating agent complexes to lumazine synthase isolated from Aquifex aeolicus (AaLS). The r(1) relaxivity of Gd(III)-DOTA-AaLS-R108C was 16.49 mM(-1)s(-1) and its r(1)/r(2) ratio was 0.52 at the magnetic field strength of 7 T. The results of 3D MR angiography demonstrated the feasibility of vasculature imaging within 2 h of intravenous injection of the agent and a significant reduction in T-1 values were observed in the tumor region 7 h post-injection in the SCC-7 flank tumor model. Our findings suggest that Gd(III)-DOTA-AaLS-R108C could serve as a potential theranostic nanoplatform at high magnetic field strength.open0

Purification and Characterization of a Sperm Motility Inhibiting Factor from Caprine Epididymal Plasma

Several studies have been reported on the occurrence of sperm motility inhibiting factors in the male reproductive fluids of different mammalian species, but these proteins have not been adequately purified and characterized. A novel sperm motility inhibiting factor (MIF-II) has been purified from caprine epididymal plasma (EP) by Hydroxylapatite gel adsorption chromatography, DEAE-Cellulose ion-exchange chromatography and chromatofocusing. The MIF-II has been purified to apparent homogeneity and the molecular weight estimated by Sephacryl S-300 gel filtration is 160 kDa. MIF-II is a dimeric protein, made up of two subunits each having a molecular mass of 80 kDa as shown by SDS-PAGE. The isoelectric point of MIF-II is 5.1 as determined by chromatofocusing and isoelectric focusing. It is a heat labile protein and maximal active at the pH 6.9 to 7.5. The sperm motility inhibiting protein factor at 2 µg/ml (12.5 nM) level showed maximal motility-inhibiting activity. The observation that the epididymal plasma factor lowered the intracellular cAMP level of spermatozoa in a concentration-dependent manner suggests that it may block the motility of caprine cauda spermatozoa by interfering the cAMP dependent motility function. The results revealed that the purified protein factor has the potential of sperm motility inhibition and may serve as a vaginal contraceptive. The antibody raised against the MIF-II has the potential for enhancement of forward motility of cauda-spermatozoa. This antibody may thus be useful for solving some of the problems of male infertility due to low sperm motility

Sympathetic Nervous System Reactivity in Women following Preeclamptic Pregnancies

Women who have had preeclamptic pregnancies are at risk for life‐long cardiovascular disease. However, the factors contributing to this risk have yet to be established. Sympathetic nervous system dysregulation has been proposed to contribute to cardiovascular dysfunction during preeclamptic pregnancies. Therefore, we examined muscle sympathetic nerve activity (MSNA) at baseline and during a chemoreflex stimulus in women 6–24 months postpartum following a preeclamptic pregnancy (PE; n=6, age 28±2 y, BMI 27±3 kg/m2, 17±4 months postpartum). We hypothesized that MSNA responses to apnea would be greater in PE relative to control subjects, that is, women 6–24 months following a healthy pregnancy and with no history of disordered pregnancies (HP; n=6, 31±6 y, BMI 29±5 kg/m2, 17±4 months postpartum). Integrated MSNA recordings were obtained at baseline and during a voluntary end‐inspiratory apnea. Baseline mean arterial pressure (MAP; 87±10 vs 95±10 mmHg, P=0.2), total peripheral resistance (TPR; 13±3 vs 14±1 mmHg/L/min, P=0.4), and heart rate (HR; 74±5 vs 74±13, P=0.9) were similar in PE vs HP. Baseline MSNA was higher in PE compared to HP (26±9 vs 14±6 bursts/100 heartbeats, P<0.01). The voluntary apnea was maintained for a similar duration in PE and HP (44±17 and 45±10 sec, P=0.9), without any difference in mean MAP (93±14 and 99±11, P=0.4), TPR (14±4 and 14±2, P=0.6), or HR (74±8 and 81±22, P=0.5) between groups. To discern between mild and moderate phases of chemoreflex stress, the apnea was divided into initial (i.e. first half) and latter (i.e. second half) phases for subsequent analyses. The initial phase of the apnea elicited a large increase in MSNA in the PE women which exceeded that observed in HP (37±13 vs 19±11, P=0.03, respectively). The peak sympathetic response observed in the latter half of the apnea was similar between PE and HP (56±21 vs 49±13 bursts/100hb, P=0.5). Thus, the sympathetic nervous system response to a mild chemoreflex stimulus is exaggerated in women who have had preeclampsia within the past 6–24 months relative to women without a history of preeclampsia. We have demonstrated that a recent history of preeclampsia is associated with chronic sympathetic activation as well as greater sympathetic reactivity. We propose these changes to the sympathetic nervous system contribute to the life‐long risk for cardiovascular disease in formerly preeclamptic women. Support or Funding Information Funded by the Paul Titus Fellowship, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine. This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal

A recent history of preeclampsia is associated with elevated central pulse wave velocity and muscle sympathetic outflow

We demonstrate that resting muscle sympathetic nerve activity is elevated in women with a recent history of preeclampsia relative to women who have recently had uncomplicated pregnancies and without a history of preeclampsia. Structural changes in the central arteries are associated with arterial stiffness following preeclampsia, independent of changes in the sympathetic nervous system. The structural changes are observed in these relatively young previously preeclamptic women, indicating elevated cardiovascular risk. Our data suggest that with aging (and the gradual loss of vascular protection for women, as established by others), this risk will become exaggerated compared with women who have had normal pregnancies. Preeclampsia is associated with the development of cardiovascular diseases later in life. To investigate this phenomenon, we compared established markers of cardiovascular dysregulation between previously preeclamptic women (PPE; n = 12, 13 ± 6 mo postpartum, 34 ± 6 yr) and women who had previously had an uncomplicated pregnancy [control (CTRL); n = 12, 15 ± 4 mo postpartum; 29 ± 3 yr]. We hypothesized that PPE would present with elevated arterial stiffness (assessed as central and peripheral pulse wave velocity) and muscle sympathetic nerve activity (MSNA; microneurography) and blunted baroreflex sensitivity (BRS) relative to CTRL. Blood pressure (Finometer) was similar between PPE and CTRL (mean arterial pressure: 94 ± 11 vs. 89 ± 9, P = 0.16). Central (6.92 ± 0.21 vs. 6.24 ± 0.22 m/s, P = 0.04) but not peripheral arterial stiffness (7.52 ± 0.19 vs. 7.09 ± 0.19 m/s, P = 0.13) was elevated in PPE versus CTRL (values normalized to MAP). MSNA was also elevated in PPE versus CTRL (22 ± 7 vs. 13 ± 5 bursts/min, P = 0.01), although this was independent of arterial stiffness (central: r 2  = 0.01, P = 0.74; peripheral: r 2  = 0.01, P = 0.74). Cardiovagal BRS was blunted in PPE versus CTRL (15 ± 5 vs. 28 ± 1 ms/mmHg, P = 0.01), whereas sympathetic vascular BRS was similar (−3.2 ± 0.9 vs. −3.1 ± 1.4 bursts·100 hb −1 ·mmHg −1 , P  = 0.88). Cardiovagal and sympathetic BRS were inversely correlated in both CTRL ( r 2  = 0.43; P = 0.05) and PPE ( r 2  = 0.69; P = 0.04), supporting a compensatory mechanism resulting in normal blood pressures in both groups. Overall, these data indicate that PPE retain their ability to buffer elevated MSNA. We propose that the higher incidence of cardiovascular disease observed later in life in PPE results from this arterial stiffness, combined with the loss of protective vascular mechanisms and the “unmasking” of high MSNA. NEW & NOTEWORTHY We demonstrate that resting muscle sympathetic nerve activity is elevated in women with a recent history of preeclampsia relative to women who have recently had uncomplicated pregnancies and without a history of preeclampsia. Structural changes in the central arteries are associated with arterial stiffness following preeclampsia, independent of changes in the sympathetic nervous system. The structural changes are observed in these relatively young previously preeclamptic women, indicating elevated cardiovascular risk. Our data suggest that with aging (and the gradual loss of vascular protection for women, as established by others), this risk will become exaggerated compared with women who have had normal pregnancies. Listen to this article’s corresponding podcast at: https://ajpheart.podbean.com/e/behind-the-bench-episode-4/

Sympathetic Responses to Isometric Handgrip Exercise in Women following Preeclamptic Pregnancies

Women who have had preeclamptic (PE) pregnancies are at increased risk for developing cardiovascular diseases later in life. One potential mechanism that may mediate this increased risk is sympathetic dysregulation. Indeed, there is evidence for elevated muscle sympathetic nerve activity (MSNA) both during and following PE pregnancies. Moreover, previously PE (PPE) women may demonstrate impaired MSNA responses during stress, although this has only been examined to a limited extent. Therefore, we tested the hypothesis that MSNA responses to isometric hand grip exercise (HG) would be greater in PPE women (n=6, age 31±6 years, BMI 29±5 kg/m , 17±4 months postpartum) compared with women who had a healthy pregnancy (HP; n=8, age 29±2, BMI 25±4 kg/m , 14±4 months postpartum). MSNA (peroneal nerve microneurography), mean arterial pressure (MAP; finger photoplethysmography), and total peripheral resistance (TPR; MAP/cardiac output), were assessed at baseline, during a 2-min HG protocol, and during 2-min post-exercise circulatory occlusion (PECO). As previously reported, baseline MSNA was higher in PPE than HP (22±7 vs 13±5 bursts/min, P=0.01). Baseline MAP was not different between PPE and HP (94±11 vs 89±9 mmHg, P=0.23), nor was TPR (13±3 vs 13±2 mmHg/L/min, P=0.63). During HG, MSNA was greater in PPE than HP (24±8 vs 16±6 bursts/min, P=0.03), whereas MAP was not different between PPE and HP (95±12 vs 95±11 mmHg, P=0.99), nor was TPR (13±3 vs 14±2 mmHg/L/min, P=0.39). During PECO, no differences were observed between PPE and HP women in MSNA (26±8 vs 18±6 bursts/min, P=0.08), MAP (93±12 vs 96±12 mmHg, P=0.70), or TPR (12±3 vs 15±2 mmHg/L/min, P=0.18). These findings indicate that PPE women demonstrate exaggerated MSNA during isometric HG exercise relative to HP women, although the role of the metaboreflex in mediating this effect, as assessed using PECO, remains unclear. Importantly, these data also demonstrate that young PPE women were able to buffer the deleterious cardiovascular outcomes of elevated MSNA such that MAP and TPR outcomes were similar to age-matched HP women during all conditions