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The study examines the potential for Epicurean eating to offer fresh perspectives on the predictive value of mindful eating. This research seeks to ascertain whether accounting for Epicurean eating (or its antithesis, supersizing), could influence the previously identified negative relationship between mindful eating and grazing habits. In a cross-sectional study, 419 participants completed questionnaires on epicurean eating, grazing, and mindful eating. The findings suggested mindful eating and epicurean eating were significantly associated with grazing, with both variables accounting for a significant amount of variance in grazing. Further analysis of the mindful eating subscales showed that eating without distraction, eating with awareness, and hunger and satiety cues accounted for this association with grazing when epicurean eating was included. Finally, whilst eating without distraction, eating with awareness, and hunger and satiety cues were associated with grazing, preference for supersizing did not account for a significant amount of variance in the relationship with grazing. The complex interplay between grazing and mindful eating becomes more apparent when considering the influence of epicurean eating. Exploring cross-cultural factors through additional research could provide valuable insights into the dynamics of epicurean eating and grazing. Simultaneously, incorporating alternative mindful eating scales may yield a more nuanced interpretation of mindful eating. Collectively, these avenues of inquiry warrant further investigation. Limitations and future directions are discussed.

Existing research investigating gay men’s eating behavior has focused on stereotypes and body image, rather than to understand why disordered eating is prevalent in gay men. The current study adopted a qualitative approach and employed interview methodology to explore gay men’s attitudes, feelings and experiences of their eating behavior, and the potential link to mindfulness and self-compassion. Twenty gay men aged from 21 to 51 years were interviewed using an interview schedule with open-ended questions. Three main themes emerged from the transcript data sets: “Lean to be Seen,” “Sod it ‘I’ll Have a Pizza,” and “You Can’t Sit with Us.” The first theme was developed following responses that participant’s eating behavior and exercise engagement were influenced by their perceived attractiveness by the gay community. All participants spoke of achieving or maintaining a slim or muscular body type and adopted their eating behavior or exercise regime to reach corresponding goals. The second theme relates to the lack of acceptance felt from the gay community upon not conforming to the bodily expectations set out by the community. The third theme relates to the conflicts in participants’ attitudes around how exercising and eating healthily would improve their mental well-being; but that they also would give preference to calorie dense foods to reduce stress. These reflections are observed through a context of self-kindness and self-compassion and are seen to be related to increased feelings of self-criticism and body dissatisfaction. The limitations and implication for this research and suggestions for future research are discussed.

Background Recent evidence suggests that autonomic nervous system activity could be involved in the pathophysiology of sickle cell disease, but it is unclear whether differences in autonomic nervous system activity are detectable during steady state in patients with mild and severe disease. The aim of the present study was to compare the autonomic nervous system activity, blood rheology, and inflammation in patients with sickle cell anemia according to the frequency of acute pain crisis.Design and Methods Twenty-four healthy volunteers, 20 patients with sickle cell anemia with milder disease, and 15 patients with sickle cell anemia with more severe disease were recruited. Milder disease was defined as having no pain crisis within the previous year. More severe disease was defined as having had within the previous year three or more pain crises which were documented by a physician and required treatment with narcotics. The autonomic nervous system activity was determined by spectral analysis of nocturnal heart rate variability. Blood viscosity determination and measurements of several inflammatory markers (interleukin-6, soluble vascular cell adhesion molecule-1, soluble CD40 ligand and sL-selectin) were made on blood samples collected in steady-state conditions.Results Results showed that: 1) patients who had suffered more frequent pain crises had lower parasympathetic activity and greater sympatho-vagal imbalance than both controls and patients with milder disease. However, when adjusted for age, no significant difference was detected between the two sickle cell anemia patient groups; 2) patients who had suffered more frequent pain crises had higher blood viscosity than patients with milder disease, and this was not dependent on age.Conclusions Results from the present study indicate that both the autonomic nervous system activity and blood viscosity are impaired in patients with sickle cell anemia exhibiting high frequency of pain crisis in comparison with those who did not experience a crisis within the previous year.

What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α 2 -adrenergic agonist, 10-min loading infusion of 0.225 µg·kg -1 ; maintenance infusion of 0.1-0.5 µg·kg·h -1 ) in six healthy individuals (5 females, 27 ± 6 yr). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (liquid chromatography-tandem mass spectrometry) levels at baseline and the dexmedetomidine maintenance infusion. Linear mixed-model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], P = 0.002), total AP clusters (β = 0.90 [0.22], P = 0.005), and AP frequency (β = 0.11 [0.03], P = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], P = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], P = 0.030) and AP frequency (β = 2.66 [0.81], P = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation. NEW & NOTEWORTHY The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α 2 -adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.

Memory consolidation involves the synchronous reactivation of hippocampal cells active during recent experience in sleep sharp-wave ripples (SWRs). How this increase in firing rates and synchrony after learning is counterbalanced to preserve network stability is not understood. We discovered a network event generated by an intrahippocampal circuit formed by a subset of CA2 pyramidal cells to cholecystokinin-expressing (CCK+) basket cells, which fire a barrage of action potentials ("BARR") during non-rapid eye movement sleep. CA1 neurons and assemblies that increased their activity during learning were reactivated during SWRs but inhibited during BARRs. The initial increase in reactivation during SWRs returned to baseline through sleep. This trend was abolished by silencing CCK+ basket cells during BARRs, resulting in higher synchrony of CA1 assemblies and impaired memory consolidation.

The present study investigated the impact of central α 2 -adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α 2 -adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg -1 ; maintenance infusion of 0.1-0.5 µg kg h -1 ) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats -1 , P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats -1 ; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats -1 , P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg -1 ; P = 0.008). These data suggest that α 2 -adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α 2 -adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α 2 -adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological diseases, such as Alzheimer's disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multilayer hippocampal silicon probes. Both the local field potential features and firing patterns of pyramidal cells and interneurons were similar in the mouse and human. We found that as IEDs emerged from the CA3-1 circuits, they recruited pyramidal cells and silenced interneurons, followed by post-IED suppression. IEDs suppressed the incidence and altered the properties of physiological sharp-wave ripples, altered their physiological properties, and interfered with the replay of place field sequences in a maze. In addition, IEDs in AD mice inversely correlated with daily memory performance. Together, our work implies that IEDs may present a common and epilepsy-independent phenomenon in neurodegenerative diseases that perturbs hippocampal-cortical communication and interferes with memory.

Traditionally considered a homogeneous cell type, hippocampal pyramidal cells have been recently shown to be highly diverse. However, how this cellular diversity relates to the different hippocampal network computations that support memory-guided behavior is not yet known. We show that the anatomical identity of pyramidal cells is a major organizing principle of CA1 assembly dynamics, the emergence of memory replay, and cortical projection patterns in rats. Segregated pyramidal cell subpopulations encoded trajectory and choice-specific information or tracked changes in reward configuration respectively, and their activity was selectively read out by different cortical targets. Furthermore, distinct hippocampo-cortical assemblies coordinated the reactivation of complementary memory representations. These findings reveal the existence of specialized hippocampo-cortical subcircuits and provide a cellular mechanism that supports the computational flexibility and memory capacities of these structures., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Women with uterine fibroids (UF), benign tumors of the myometrium, have a higher prevalence of hypertension than women without UF. The cause for this relationship is unclear. Muscle sympathetic nerve activity (MSNA) is a regulator of arterial blood pressure, and it is possible that variations in MSNA predispose women with UF to develop hypertension. The purpose of this study was to assess baseline blood pressure and MSNA and the relationships between MSNA and systemic hemodynamics in women with and without UF. We measured blood pressure (brachial intra-arterial line), MSNA (microneurography), and systemic hemodynamics (total peripheral resistance and cardiac output) at rest in 14 healthy, normotensive, premenopausal women with UF (42 ± 2 years old) and 9 healthy, normotensive, premenopausal women without UF (41 ± 2 years old). Baseline blood pressure and MSNA did not differ between groups (p > 0.05 for both). In women with UF, there was a positive correlation between MSNA and total peripheral resistance (r = 0.75, p = 0.02), as well as a negative correlation between MSNA and cardiac output (r = -0.73, p = 0.03). In contrast, these relationships were not seen in women without UF (p > 0.05 for both relationships). These data suggest that autonomic interactions with systemic hemodynamics, and thus blood pressure regulation, are different in healthy women with UF compared to healthy women without UF., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Prenatal alcohol exposure (PAE) leads to profound deficits in spatial memory and synaptic and cellular alterations to the hippocampus that last into adulthood. Neurons in the hippocampus called place cells discharge as an animal enters specific places in an environment, establish distinct ensemble codes for familiar and novel places, and are modulated by local theta rhythms. Spatial memory is thought to critically depend on the integrity of hippocampal place cell firing. Therefore, we tested the hypothesis that hippocampal place cell firing is impaired after PAE by performing in vivo recordings from the hippocampi (CA1 and CA3) of moderate PAE and control adult rats. Our results show that hippocampal CA3 neurons from PAE rats have reduced spatial tuning. Second, CA1 and CA3 neurons from PAE rats are less likely to orthogonalize their firing between directions of travel on a linear track and between changes in contextual stimuli in an open arena compared to control neurons. Lastly, reductions in the number of hippocampal place cells exhibiting significant theta rhythmicity and phase precession were observed, which may suggest changes to hippocampal microcircuit function. Together, the reduced spatial tuning and sensitivity to contextual changes provide a neural systems-level mechanism to explain spatial memory impairment after moderate PAE., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Studies demonstrate an association between aortic hemodynamics and cognitive function. The impact of pregnancy history on this association is unknown., Methods: Postmenopausal women (age 59 ± 5 years; years since last pregnancy 35 ± 3) with either a history of preeclampsia (PE; n = 34) or a history of a normotensive pregnancy (NP; n = 30) underwent cognitive testing: Letter-Number Sequencing, Digit Span, Trail Making Test, and letter and category fluency. Applanation tonometry was used to derive aortic systolic and diastolic blood pressure and augmentation index., Results: Distribution of cognitive scores and aortic hemodynamic measures was similar between the PE and NP groups. Principal component (PC) analysis was used to reduce the 3 aortic hemodynamic measures and the 5 cognitive variables to single summary indices, each representing a weighted average of their respective constituent variables. Using a multivariable linear model based on these PCs that adjusted for pregnancy history and body mass index, the composite index of aortic hemodynamics was associated with the summary cognitive index, whether taking into account a potential interaction with pregnancy history (P = 0.035) or not (P = 0.026) (interaction P = 0.178). Multivariable modeling of individual cognitive tests revealed a differential association for letter fluency by pregnancy history (test for interaction P = 0.023); this score correlated with the aortic hemodynamic index in the PE (partial R2 = 0.20), but not the NP (partial R2 = 0.00) group., Conclusions: Elevated aortic hemodynamics may negatively impact cognitive function in postmenopausal women with specific executive functions, such as letter fluency, being impacted more by a pregnancy history of PE., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

New Findings: What is the central question of this study? What is the role of β 2 -adrenergic receptor (β 2 AR) vasodilatation in older postmenopausal women as compared to premenopausal women and the role of nitric oxide (NO) in β 2 AR-mediated vasodilatation in both groups of women? What is the main finding and its importance? β 2 AR responsiveness is blunted in postmenopausal women compared to young premenopausal women. Additionally, NO may contribute to β 2 AR-mediated vasodilatation in young premenopausal women., Abstract: β 2 -Adrenergic receptor (β 2 AR)-mediated vasodilatation, which is partially dependent on nitric oxide (NO) formation, is blunted in men at risk for developing hypertension. However, the role of β 2 AR vasodilatation in hypertension pathophysiology in ageing postmenopausal women is unclear. Therefore, the goals of this study were to determine if forearm vasodilatation to the selective β 2 AR agonist terbutaline is blunted in older postmenopausal women (59 ± 4 years) compared to young premenopausal women (27 ± 3 years) and to assess NO contribution to β 2 AR-mediated vasodilatation in both groups of women. Forearm blood flow (FBF) and forearm vascular conductance (FVC) were measured using venous occlusion plethysmography at baseline and during intra-arterial infusions of terbutaline at 0.1-2.0 µg (100 ml tissue) -1  min -1 with and without the NO synthase inhibitor l-N G -monomethylarginine (l-NMMA). Mean arterial pressure was significantly greater in postmenopausal women than in young women at baseline (P = 0.01). Baseline FBF and FVC did not differ between young and postmenopausal women (P > 0.05) and rose significantly within each group during terbutaline infusion (P < 0.05). There were significant group × dose interactions for FBF (P = 0.01) and FVC (P = 0.001), indicating vasodilator responses were lower in postmenopausal women. In young women, FVC response to the highest dose of terbutaline tended to be lower with l-NMMA co-infusion vs. without l-NMMA (P = 0.05). There were no significant decreases in FBF or FVC responses to terbutaline in postmenopausal women with l-NMMA co-infusion (P > 0.05 for all). These data suggest that β 2 AR responsiveness is blunted in postmenopausal women compared to young premenopausal women, and that NO may contribute to β 2 AR-mediated vasodilatation in young premenopausal women., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Head direction (HD) cells, which fire action potentials whenever an animal points its head in a particular direction, are thought to subserve the animal's sense of spatial orientation. HD cells are found prominently in several thalamo-cortical regions including anterior thalamic nuclei, postsubiculum, medial entorhinal cortex, parasubiculum, and the parietal cortex. While a number of methods in neural decoding have been developed to assess the dynamics of spatial signals within thalamo-cortical regions, studies conducting a quantitative comparison of machine learning and statistical model-based decoding methods on HD cell activity are currently lacking. Here, we compare statistical model-based and machine learning approaches by assessing decoding accuracy and evaluate variables that contribute to population coding across thalamo-cortical HD cells., (Copyright © 2019 Xu, Wu, Winter, Mehlman, Butler, Simmons, Harvey, Berkowitz, Chen, Taube, Wilber and Clark.)

The consumption of alcohol during gestation is detrimental to the developing central nervous system. One functional outcome of this exposure is impaired spatial processing, defined as sensing and integrating information pertaining to spatial navigation and spatial memory. The hippocampus, entorhinal cortex, and anterior thalamus are brain regions implicated in spatial processing and are highly susceptible to the effects of developmental alcohol exposure. Some of the observed effects of alcohol on spatial processing may be attributed to changes at the synaptic to circuit level. In this review, we first describe the impact of developmental alcohol exposure on spatial behavior followed by a summary of the development of brain areas involved in spatial processing. We then provide an examination of the consequences of prenatal and early postnatal alcohol exposure in rodents on hippocampal, anterior thalamus, and entorhinal cortex-dependent spatial processing from the cellular to behavioral level. We conclude by highlighting several unanswered questions which may provide a framework for future investigation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Preeclampsia (PE) is a hypertensive disorder of pregnancy described as a condition of excessive sympathoexcitation. PE places a woman at increased risk for lifelong hypertension and cognitive impairment. Cerebral blood velocity is blunted in response to a vasoactive stimulus in women with a history of PE. This study investigated how a sympathoexcitatory stimulus affects cerebral blood velocity in women with a history of PE. Middle cerebral artery blood velocity (MCAv) and beat-to-beat mean arterial blood pressure (MAP) were measured in postmenopausal women with a history of PE ( n = 21; age = 59 ± 5 yr) and a history of a normotensive pregnancy (NP; n = 27; age = 58 ± 4 yr), at baseline, during isometric handgrip to fatigue (IHG) followed by postexercise ischemia (PEI), and a recovery period (REC). Baseline MAP and MAP responses to IHG and PEI did not differ between groups. MCAv at baseline and throughout the stimulus was lower in PE women compared with NP women ( P < 0.05 for all). MCAv increased during IHG in both groups ( P < 0.05). This increase in MCAv was greater in PE compared with NP women during IHG and REC (IHG: PE 13 ± 2% vs. NP 9 ± 2%; REC: PE 3 ± 2% vs. NP -2 ± 2%; P < 0.05 for both). Thus, a history of PE is associated with low baseline cerebral blood velocity but an augmented response to a sympathoexcitatory stimulus. These changes in cerebral blood flow regulation may lead to an increased risk for cognitive impairment in women with a history of PE.

Objective: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease., Methods: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17β-estradiol, or placebo [PLA])., Results: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group., Conclusion: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Spatial navigation is impaired in early stages of Alzheimer's disease, and may be a defining behavioral marker of preclinical AD. A new rat model (TgF344-AD) of AD overcomes many limitations of other rodent models, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n = 16) and Fischer 344 (n = 12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4-5 months, with deficits in the hidden platform task emerging at 7-8 months and becoming significantly pronounced at 10-11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and searched a wider area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable navigational deficits to those found in individuals with preclinical-AD.

Reduced cerebrovascular reactivity to a vasoactive stimulus is associated with age-related diseases such as stroke and cognitive decline. Habitual exercise is protective against cognitive decline and is associated with reduced stiffness of the large central arteries that perfuse the brain. In this context, we evaluated the age-related differences in cerebrovascular reactivity in healthy adults who habitually exercise. In addition, we sought to determine the association between central arterial stiffness and cerebrovascular reactivity. We recruited 22 young (YA: age = 27 ± 5 years, range 18-35 years) and 21 older (OA: age = 60 ± 4 years, range 56-68 years) habitual exercisers who partake in at least 150 min of structured aerobic exercise each week. Middle cerebral artery velocity (MCAv) was recorded using transcranial Doppler ultrasound. In order to assess cerebrovascular reactivity, MCAv, end-tidal carbon dioxide (ETCO 2 ), and mean arterial pressure (MAP) were continuously recorded at rest and during stepwise elevations of 2, 4, and 6% inhaled CO 2 . Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Central arterial stiffness was assessed using carotid-femoral pulse wave velocity (PWV). Older adults had higher PWV (YA: 6.2 ± 1.2 m/s; OA: 7.5 ± 1.3 m/s; p < 0.05) compared with young adults. MCAv and CVCi reactivity to hypercapnia were not different between young and older adults (MCAv reactivity, YA: 2.0 ± 0.2 cm/s/mmHg; OA: 2.0 ± 0.2 cm/s/mmHg; p = 0.77, CVCi reactivity, YA: 0.018 ± 0.002 cm/s/mmHg 2 ; OA: 0.015 ± 0.001 cm/s/mmHg 2 ; p = 0.27); however, older adults demonstrated higher MAP reactivity to hypercapnia (YA: 0.4 ± 0.1 mmHg/mmHg; OA: 0.7 ± 0.1 mmHg/mmHg; p < 0.05). There were no associations between PWV and cerebrovascular reactivity (range: r = 0.00-0.39; p = 0.07-0.99). Our results demonstrate that cerebrovascular reactivity was not different between young and older adults who habitually exercise; however, MAP reactivity was augmented in older adults. This suggests an age-associated difference in the reliance on MAP to increase cerebral blood flow during hypercapnia.

The vestibular system provides a crucial component of place-cell and head-direction cell activity [1-7]. Otolith signals are necessary for head-direction signal stability and associated behavior [8, 9], and the head-direction signal's contribution to parahippocampal spatial representations [10-14] suggests that place cells may also require otolithic information. Here, we demonstrate that self-movement information from the otolith organs is necessary for the development of stable place fields within and across sessions. Place cells in otoconia-deficient tilted mice showed reduced spatial coherence and formed place fields that were located closer to environmental boundaries, relative to those of control mice. These differences reveal an important otolithic contribution to place-cell functioning and provide insight into the cognitive deficits associated with otolith dysfunction., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia during simulated blood loss in humans would cause impairments in cerebral blood flow control. Ten healthy subjects (32 ± 6 years, BMI 27 ± 2 kg·m -2 ) were exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, -15, -30, and -45 mmHg) during both normoxia and hypoxia (F i O 2  = 0.12-0.15 O 2 titrated to an SaO 2 of ~85%). Physiological responses during both protocols were expressed as absolute changes from baseline, one subject was excluded from analysis due to presyncope during the first stage of LBNP during hypoxia. LBNP induced greater reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at -45 mmHg: -20 ± 3 vs. -5 ± 3 mmHg, P < 0.01). Despite differences in MAP, middle cerebral artery velocity responses (MCAv) were similar between protocols (P = 0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia (main effect, P = 0.04). Low frequency MAP (at -45 mmHg: 17 ± 5 vs. 0 ± 5 mmHg 2 , P = 0.01) and MCAv (at -45 mmHg: 4 ± 2 vs. -1 ± 1 cm·s -2 , P = 0.04) spectral power density, as well as low frequency MAP-mean MCAv transfer function gain (at -30 mmHg: 0.09 ± 0.06 vs. -0.07 ± 0.06 cm·s -1 ·mmHg -1 , P = 0.04) increased more during hypoxia versus normoxia. Contrary to our hypothesis, these findings support the notion that cerebral blood flow control is not impaired during exposure to acute hypoxia and progressive central hypovolemia despite lower MAP as a result of compensated increases in cerebral conductance and flow variability., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Cerebrovascular reactivity (CVR) is reduced in patients with cognitive decline. Women with a history of preeclampsia are at increased risk for cognitive decline. This study examined an association between pregnancy history and CVR using a subgroup of 40 age- and parity-matched pairs of women having histories of preeclampsia (n=27) or normotensive pregnancy (n=29) and the association of activated blood elements with CVR. Middle cerebral artery velocity was measured by Doppler ultrasound before and during hypercapnia to assess CVR. Thirty-eight parameters of blood cellular elements, microvesicles, and cell-cell interactions measured in venous blood were assessed for association with CVR using principal component analysis. Middle cerebral artery velocity was lower in the preeclampsia compared with the normotensive group at baseline (63±4 versus 73±3 cm/s; P =0.047) and during hypercapnia ( P =0.013-0.056). CVR was significantly lower in the preeclampsia compared with the normotensive group (2.1±1.3 versus 2.9±1.1 cm·s·mm Hg; P =0.009). Globally, the association of the 7 identified principal components with preeclampsia ( P =0.107) and with baseline middle cerebral artery velocity ( P =0.067) did not reach statistical significance. The interaction between pregnancy history and principal components with respect to CVR ( P =0.084) was driven by a nominally significant interaction between preeclampsia and the individual principal component defined by blood elements, platelet aggregation, and interactions of platelets with monocytes and granulocytes ( P =0.008). These results suggest that having a history of preeclampsia negatively affects the cerebral circulation years beyond the pregnancy and that this effect was associated with activated blood elements., (© 2017 American Heart Association, Inc.)

Central (aortic) blood pressure and aortic pulse wave characteristics are measures of cardiovascular health, predictive of cardiovascular mortality. Previous studies have compared aortic hemodynamics in women who do and do not take menopausal hormone therapy, but characteristics of these parameters following cessation of treatment have not been defined. Therefore, the purpose of this study was to define aortic pulse wave characteristics in postmenopausal women with and without a history of menopausal hormone therapy use. Pulse wave analysis was conducted on 67 women who had participated in the randomized, double-blind, placebo-controlled Kronos Early Estrogen Prevention Study (KEEPS), 3 years subsequent to the four-year treatment period. Treatment was oral conjugated equine estrogen (0.45 mg/day; n  = 18); transdermal 17 β -estradiol (50  μ g/day; n  = 23) each with oral micronized progesterone (Prometrium 200 mg); and placebo pills and patch ( n  = 26). At post-treatment, median age (60 years) and body mass index (27 kg/m 2 ) did not differ across prior treatment assignment. Aortic blood pressures (median systolic 115 mm Hg and diastolic 76 mm Hg) and augmentation index (median 33%) did not differ among women across prior treatment assignment. These results suggest that these doses and formulations of menopausal hormone therapy had no long-term effects on central vascular function 3 years after cessation of treatment., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: While many of these agents have been compared in prospective clinical trials, the gemcitabine/platinumbased regimens have not been compared in a prospective, randomized clinical trial. While bothgemcitabine/carboplatin and gemcitabine/cisplatin have a similar ORR in separate clinical trials, the tworegimens have never been directly been compared. With overlapping dose-limiting toxicity of thrombocytopenia, the gemcitabine/carboplatin regimen has been challenging to employ in the clinical setting in previously treated ovarian cancer patients and is often associated with treatment delays and/or dose reductions. Gemcitabine/cisplatin can also be a challenge due to its dose limiting neuropathy and renal toxicity, especially in previously treated patients. In the absence of any prospective, head to head comparison this retrospective study was embarked upon to compare the response rate and toxicity profiles of gemcitabine/cisplatin verses gemcitabine/carboplatin for the treatment of platinum-sensitive verses platinum-resistant recurrent ovarian cancer., Methods: This was a retrospective chart review study that identified patients that had received either gemcitabine/cisplatin or gemcitabine/carboplatin for treatment of recurrent ovarian cancer and compared documented hematological and non-hematological toxicity and response based on RECIST (v1.1). Data was evaluated based upon platinum sensitivity/resistance as well., Results: A total of 93 patients were identified that had received a gemcitabine/platinum regimen with 48 with recurrent ovarian cancer that were included in the study. There were 21 patients in the gemcitabine/cisplatin arm and 27 patients identified in the gemcitabine/carboplatin arm. Objective response rate (ORR) was greater in platinum-sensitive patients that received gemcitabine/carboplatin compared to gemcitabine/cisplatin (8 (67%) vs 2 (25%), p  < 0.05). Conversely, ORR was greater in platinum-resistant patients treated with gemcitabine/cisplatin (4 (57%) vs 1 (25%), NS). Mean time to progression was greater in gemcitabine/cisplatin patients (7.2 vs 5.1 months, p  < 0.03). Patients treated with gemcitabine/carboplatin discontinued due to toxicity at a greater rate (8 (33%) vs 5 (24%)). Specifically gemcitabine/carboplatin had a greater incidence (85%) of grade 2 or greater leukopenia, thrombocytopenia, and neutropenia compared to gemcitabine/cisplatin (19%) However, there was no significant difference in dose reductions, treatment delays, or granulocyte-colony stimulating factor (G-CSF) administration between regimens., Conclusions: Gemcitabine/cisplatin appears to have greater efficacy in platinum-resistant patients, while gemcitabine/carboplatin seems to have greater efficacy in platinum-sensitive patients. Overall, gemcitabine/carboplatin was associated with a greater incidence of myelosuppression and discontinuation due to toxicity. Similar to findings in endometrial cancer, gemcitabine/cisplatin may have benefit specifically in platinum-resistant ovarian cancer.

Ghrelin plays a key role in appetite, energy homeostasis, and glucose regulation. Recent evidence suggests ghrelin suppresses inflammation in obesity; however, whether this is modulated by the acylated and/or des-acylated peptide is unclear. We used mice deficient in acylated ghrelin [ghrelin octanoyl-acyltransferase (GOAT) knockout (KO) mice], wild-type (WT) littermates, and C57BL/6 mice to examine the endogenous and exogenous effects of acyl and des-acyl ghrelin on inflammatory profiles under nonobese and obese conditions. We demonstrate that in the spleen, both ghrelin and GOAT are localized primarily in the red pulp. Importantly, in the thymus, ghrelin was predominantly localized to the medulla, whereas GOAT was found in the cortex, implying differing roles in T cell development. Acute exogenous treatment with acyl/des-acyl ghrelin suppressed macrophage numbers in spleen and thymus in obese mice, whereas only acyl ghrelin increased CD3+ T cells in the thymus in mice fed both chow and a high-fat-diet (HFD). Consistent with this result, macrophages were increased in the spleen of KO mice on a HFD. Whereas there was no difference in CD3+ T cells in the plasma, spleen, or thymus of WT vs KO mice, KO chow and HFD-fed mice displayed decreased leukocytes. Our results suggest that the acylation status affects the anti-inflammatory properties of ghrelin under chow and HFD conditions., (Copyright © 2017 Endocrine Society.)

Purpose: The blood pressure "error signal" represents the difference between an individual's mean diastolic blood pressure and the diastolic blood pressure at which 50% of cardiac cycles are associated with a muscle sympathetic nerve activity burst (the "T50"). In this study we evaluated whether T50 and the error signal related to the extent of change in blood pressure during autonomic blockade in young and older women, to study potential differences in sympathetic neural mechanisms regulating blood pressure before and after menopause., Methods: We measured muscle sympathetic nerve activity and blood pressure in 12 premenopausal (25 ± 1 years) and 12 postmenopausal women (61 ± 2 years) before and during complete autonomic blockade with trimethaphan camsylate., Results: At baseline, young women had a negative error signal (-8 ± 1 versus 2 ± 1 mmHg, p < 0.001; respectively) and lower muscle sympathetic nerve activity (15 ± 1 versus 33 ± 3 bursts/min, p < 0.001; respectively) than older women. The change in diastolic blood pressure after autonomic blockade was associated with baseline T50 in older women (r = -0.725, p = 0.008) but not in young women (r = -0.337, p = 0.29). Women with the most negative error signal had the lowest muscle sympathetic nerve activity in both groups (young: r = 0.886, p < 0.001; older: r = 0.870, p < 0.001)., Conclusions: Our results suggest that there are differences in baroreflex control of muscle sympathetic nerve activity between young and older women, using the T50 and error signal analysis. This approach provides further information on autonomic control of blood pressure in women.

Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede the appearance of clinically defined hypertension but the relationship of aortic hemodynamics to development of WMH in women is not known. Therefore, this study aimed to characterize aortic hemodynamics in relationship to WMH in postmenopausal women. Aortic systolic and diastolic blood pressure (BP), aortic augmentation index (Alx) and aortic round trip travel time (Aortic T R ) by tonometry were examined in 53 postmenopausal women (age 60 ± 2 years). WMH was calculated from fluid-attenuated inversion recovery MRI using a semi-automated segmentation algorithm. WMH as a fraction of total white matter volume positively associated with aortic systolic BP (regression coefficient = 0.018; p = 0.04) after adjusting for age. In addition, WMH fraction was positively associated with AIx (0.025; p = 0.04), and inversely associated with Aortic T R (-0.015; p = 0.04) after adjusting for age. Our results suggest that assessing aortic hemodynamics may identify individuals at risk for accelerated development of WMH and guide early treatment to reduce WMH burden and cognitive impairment in the future.

The limbic thalamus, specifically the anterior thalamic nuclei (ATN), contains brain signals including that of head direction cells, which fire as a function of an animal's directional orientation in an environment. Recent work has suggested that this directional orientation information stemming from the ATN contributes to the generation of hippocampal and parahippocampal spatial representations, and may contribute to the establishment of unique spatial representations in radially oriented tasks such as the radial arm maze. While previous studies have shown that ATN lesions can impair spatial working memory performance in the radial maze, little work has been done to investigate spatial reference memory in a discrimination task variant. Further, while previous studies have shown that ATN lesions can impair performance in the radial maze, these studies produced the ATN lesions prior to training. It is therefore unclear whether the ATN lesions disrupted acquisition or retention of radial maze performance. Here, we tested the role of ATN signaling in a previously learned spatial discrimination task on a radial arm maze. Rats were first trained to asymptotic levels in a task in which two maze arms were consistently baited across training. After 24 h, animals received muscimol inactivation of the ATN before a 4 trial probe test. We report impairments in post-inactivation trials, suggesting that signals from the ATN modulate the use of a previously acquired spatial discrimination in the radial-arm maze. The results are discussed in relation to the thalamo-cortical limbic circuits involved in spatial information processing, with an emphasis on the head direction signal.

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure ( P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women ( P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women ( P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women ( P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group ( P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women. NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women., (Copyright © 2017 the American Physiological Society.)

Hypertensive pregnancy (HTNP) is a risk factor for future cardiovascular disease. Exaggerated cardiovascular responses to physical stress are also considered an independent marker of cardiovascular disease risk. However, there are limited data regarding the blood pressure (BP) responses to acute stress in women, who have a history of HTNP. Hence, the aim of the study is to compare BP responses to a physical stress in postmenopausal women with a history of HTNP to age- and parity-matched women with a history of normotensive pregnancy (NP). Beat-to-beat BP and heart rate was recorded in 64 postmenopausal women with [age = 58.5 (55.2, 62.2) yr, where values are the median, 25th percentile, and 75th percentile] and without [age = 59.4 (55.9, 62.4) yr] a history of HTNP before and during isometric handgrip (IHG) exercise (30% of maximal voluntary contraction) to fatigue. Muscle metaboreflex was measured during postexercise ischemia following IHG exercise. BP variables increased similarly in response to IHG exercise [systolic: NP = 11.5 (8.9, 17.6) %, HTNP = 11.3 (9.5, 15.9) %; diastolic NP = 11.2 (7.9, 13.3) %, HTNP = 9.5 (7.1, 14.3) %; mean blood pressure: NP = 9.8 (5.0, 13.6) %, and HTNP = 7.2 (4.4, 10.4) %] and postexercise ischemia [systolic: NP = 14.1 (10.3, 23.0) %, HTNP = 15.8 (10.6, 21.4) %; diastolic NP = 12.2 (4.8, 17.0) %, HTNP = 10.4 (5.3, 17.1) %; and mean blood pressure: NP = 11.1 (6.1, 17.9) %, HTNP = 9.4 (2.9, 14.8) %] in both groups. Although having a history of HTNP is associated with future cardiovascular disease risk, results from this study suggest that the risk may not be manifested through altered cardiovascular metaboreflex response to physical stressors., (Copyright © 2017 the American Physiological Society.)

The anterior and lateral thalamus has long been considered to play an important role in spatial and mnemonic cognitive functions; however, it remains unclear whether each region makes a unique contribution to spatial information processing. We begin by reviewing evidence from anatomical studies and electrophysiological recordings which suggest that at least one of the functions of the anterior thalamus is to guide spatial orientation in relation to a global or distal spatial framework, while the lateral thalamus serves to guide behavior in relation to a local or proximal framework. We conclude by reviewing experimental work using targeted manipulations (lesion or neuronal silencing) of thalamic nuclei during spatial behavior and single-unit recordings from neuronal representations of space. Our summary of this literature suggests that although the evidence strongly supports a working model of spatial information processing involving the anterior thalamus, research regarding the role of the lateral thalamus is limited and requires further attention. We therefore identify a number of major gaps in this research and suggest avenues of future study that could potentially solidify our understanding of the relative roles of anterior and lateral thalamic regions in spatial representation and memory., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Lower body negative pressure (LBNP) is often used to simulate blood loss in humans. It is unknown if cerebral blood flow responses to actual blood loss are analogous to simulated blood loss during LBNP. Nine healthy men were studied at baseline, during three levels of LBNP (5 min at -15, -30, and -45 mmHg), and during three levels of blood loss (333, 667, and 1,000 ml). LBNP and blood loss conditions were randomized. Intra-arterial mean arterial pressure (MAP) during LBNP was similar to that during blood loss (P ≥ 0.42). Central venous pressure (2.8 ± 0.7 vs. 4.0 ± 0.8, 1.2 ± 0.6 vs. 3.5 ± 0.8, and 0.2 ± 0.9 vs. 2.1 ± 0.9 mmHg for levels 1, 2, and 3, respectively, P ≤ 0.003) and stroke volume (71 ± 4 vs. 80 ± 3, 60 ± 3 vs. 74 ± 3, and 51 ± 2 vs. 68 ± 4 ml for levels 1, 2, and 3, respectively, P ≤ 0.002) were lower during LBNP than blood loss. Despite differences in central venous pressure, middle cerebral artery velocity (MCAv) and cerebrovascular conductance were similar between LBNP and blood loss at each level (MCAv at level 3: 62 ± 6 vs. 66 ± 5 cm/s, P = 0.37; cerebrovascular conductance at level 3: 0.72 ± 0.05 vs. 0.73 ± 0.05 cm·s(-1)·mmHg(-1), P = 0.53). While the slope of the MAP-MCAv relationship was slightly different between LBNP and blood loss (0.41 ± 0.03 and 0.66 ± 0.04 cm·s(-1)·mmHg(-1), respectively, P = 0.05), time domain gain between MAP and MCAv at maximal LBNP/blood loss (P = 0.23) and low-frequency MAP-mean MCAv transfer function coherence, gain, and phase were similar (P ≥ 0.10). Our results suggest that cerebral hemodynamic responses to LBNP to -45 mmHg and blood loss up to 1,000 ml follow a similar trajectory, and the arterial pressure-cerebral blood velocity relationship is not altered from baseline under these conditions.

Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. Although ≈80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine whether women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared with women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (aged 18-35 years) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53; 25±4 years) and women with natural menstrual cycles (n=74; 25±4 years). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure, 89±1 versus 85±1 mm Hg, respectively; P=0.01), although MSNA was similar in both groups (MSNA burst incidence, 16±1 versus 18±1 bursts/100 heartbeats, respectively; P=0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 versus 4.7±0.2 L/min, respectively; P=0.47) and total peripheral resistance (19.2±0.8 versus 20.0±0.9 U, respectively; P=0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use when compared with naturally menstruating women in the early follicular phase., (© 2015 American Heart Association, Inc.)

In the era of individualized medicine, gaps in knowledge remain about sex-specific risk factors, diagnostic and treatment options that might reduce mortality from cardiovascular disease (CVD) and improve outcomes for both women and men. In this review, contributions of biological mechanisms involving the sex chromosomes and the sex hormones on the cardiovascular system will be discussed in relationship to the female-specific risk factors for CVD: hypertensive disorders of pregnancy, menopause and use of hormonal therapies for contraception and menopausal symptoms. Additionally, sex-specific factors to consider in the differential diagnosis and treatment of four prevalent CVDs (hypertension, stroke, coronary artery disease and congestive heart failure) will be reviewed with emphasis on areas where additional research is needed.

Beta-adrenergic vasodilator responses may be blunted in humans who are at an increased risk for hypertension. Because menopause is associated with an increase in blood pressure, we tested the hypothesis that forearm blood flow responses to the β-adrenergic receptor agonist isoproterenol are blunted in older, postmenopausal women compared to young, premenopausal women. We used venous occlusion plethysmography to measure forearm blood flow in young premenopausal (26 ± 1 years; n = 13) and postmenopausal (61 ± 2 years; n = 12) women. Forearm blood flow and mean arterial pressure were measured at baseline and during isoproterenol infusion at 1.0, 3.0, 6.0, and 12.0 ng/100 mL tissue/min. The two groups did not differ in body mass index or mean arterial pressure. Baseline forearm blood flow was similar between young and postmenopausal women (3.7 ± 0.5 vs. 2.9 ± 0.4 mL/100 mL tissue/min, respectively; P > 0.05). At the lowest dose of isoproterenol, forearm blood flow vasodilator responses were lower in postmenopausal women compared with young women (5.8 ± 0.4 vs. 7.4 ± 0.3 mL/100 mL tissue/min, respectively; P < 0.05). Thereafter, forearm blood flow remained similar between the groups for the remaining isoproterenol doses. In conclusion, β-adrenergic receptor-mediated forearm vasodilator responses are blunted in healthy, older postmenopausal women at lower but not higher doses of isoproterenol. This suggests that in aging women, β-adrenergic receptor-mediated vasodilator responses may be blunted at a moderate level of stimulation while maximum receptor responses are preserved., (© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Background and Purpose: A variety of factors, such as pain level at rest and with activity, have been used to assess outcome of the VP procedure. However, few studies have assessed discharge disposition as a reflection of VP efficacy in the inpatient population. The purpose of this study was to compare patient disposition status before and after VP and determine what relationship exists between the treatment and patient discharge status., Materials and Methods: We performed a retrospective review of inpatients who underwent consultation for consideration of spinal augmentation for treatment of painful vertebral compression fractures. We gathered data concerning patients' demographics, living arrangements before hospitalization, discharge disposition, quantitative and qualitative pain levels, and length of hospital stay before and following VP., Results: Ninety inpatients underwent VP, 73 (81%) of whom lived independently at home before hospitalization. Of these 73 patients, 31 (42%) returned home after discharge, 9 (12%) returned home with home health care assistance, and 32 (44%) were sent to skilled nursing facilities. Six (7%) of the 90 patients resided in assisted-living centers before hospitalization; all of these patients were discharged to assisted-living or skilled nursing facilities. Eight (9%) of the 90 patients resided at skilled nursing centers before hospitalization, and all returned to nursing centers after their hospital stay. Discharge disposition was not significantly associated with preoperative pain levels at rest or with activity (P = .76 and P = .23, respectively) or with postoperative pain levels at rest or with activity (P = .08 and P = .25, respectively)., Conclusions: This study demonstrates that patients undergoing VP as inpatients are often discharged to rehabilitation centers rather than home, irrespective of their status before hospitalization or their pre- and postoperative pain levels.

Because medical students have many different learning styles, the authors, medical students at Mayo Clinic, College of Medicine researched the history of anatomical specimen procurement, reviewing topic-related film, academic literature, and novels, to write, direct, and perform a dramatization based on Robert Louis Stevenson's The Body-Snatcher. Into this performance, they incorporated dance, painting, instrumental and vocal performance, and creative writing. In preparation for the performance, each actor researched an aspect of the history of anatomy. These micro-research projects were presented in a lecture before the play. Not intended to be a research study, this descriptive article discusses how student research and ethics discussions became a theatrical production. This addition to classroom and laboratory learning addresses the deep emotional response experienced by some students and provides an avenue to understand and express these feelings. This enhanced multimodal approach to"holistic learning" could be applied to any topic in the medical school curriculum, thoroughly adding to the didactics with history, humanities, and team dynamics.

Objective: The purpose of this study was to determine the effects of intra-articular injections of high molecular weight (2000 kDa) sodium hyaluronate (HA) on the progression of articular cartilage degeneration in a rabbit partial medial meniscectomy model of osteoarthritis., Design: Six experimental groups included normal, sham operated, and operated and injected animals, the latter injected once-weekly (for two weeks or twelve weeks, beginning four weeks after surgery) with either 1% (w/v) HA or phosphate buffered saline (PBS). Following assessment of gross morphology, serial adjacent blocks of full-depth articular cartilage were prepared from the tibial condyle for analysis of total water, hydroxyproline, DNA and proteoglycan (uronic acid) content, as well as the ratio of galactosamine to glucosamine. Samples were sub-divided into inner (medial) and outer (lateral) regions., Results: No morphological differences were recognized between joints injected with PBS and those receiving HA. When analysed biochemically, there were no significant differences in hydration, hydroxyproline or DNA content between the experimental groups. In contrast, HA injection did affect changes in proteoglycan content. Expressed per tissue dry weight, uronic acid content in the operated group injected with PBS for two weeks was lower than normal (P<0.02), a result not seen in the corresponding HA injected group. After 12 weeks of PBS injections, uronic acid content (per dry weight) was higher than normal (P<0.01), an effect again not observed in the corresponding HA injected group. Results for the galactosamine: glucosamine ratio showed a reduction after 12 weeks of injections, but no differences between PBS and HA injected groups., Conclusions: Once-weekly, intra-articular injection of high molecular weight HA can prevent changes in proteoglycan content in tibial condylar articular cartilage, compared to PBS injected controls, in the rabbit partial meniscectomy model of osteoarthritis.

The field efficacy and safety of a single-dose Mycoplasma hyopneumoniae vaccine were evaluated in three-to five-week-old pigs. Two field efficacy studies were conducted, one in England with 673 pigs, and one in Germany with 719 pigs. The pigs were injected intramuscularly with either the vaccine or saline (control) at a ratio of 2:1 and reared under commercial conditions to slaughter weight. The efficacy of the vaccine was evaluated by comparing the lung lesions associated with infection with M. hyopneumoniae in the control and vaccinated animals postmortem. In both countries the vaccinated pigs had a significantly lower percentage of lung lesion scores, in England 5.7 v 10.2 per cent (P = 0.0022) and in Germany 3.9 v 7.7 per cent (P = 0.0056). In Germany the average daily weight gain (ADG) of the vaccinated pigs was significantly higher (639 g v 616 g) (P = 0.0205). In both countries and in both the treated and control animals there was a significant negative correlation between the ADG and the lung lesion score (P = 0.0001). Two safety trials were conducted, one in England and one in Germany, each with 75 pigs, and in each case 50 pigs were given the maximum batch release antigen titre of the vaccine and 25 were given saline. The safety of the vaccine was evaluated by observation for local and systemic reactions and any increases in rectal temperature. No abnormal reactions were observed in the vaccinated pigs and there was no significant difference between the mean peak rectal temperatures of the vaccinated and control pigs in either trial.

Carvedilol is a novel treatment for hypertension, having a balanced pharmacology of vasodilation and beta-receptor blockade. We present here the results of a three-way, multicenter, comparative study on the use of carvedilol, slow-release nifedipine, and atenolol in the management of essential hypertension. A total of 311 patients was entered into the study, of which 293 were randomized to one of the three treatment regimens. Full data are available on 255 patients. Systolic and diastolic blood pressure measurements, in both sitting and standing positions, were taken, together with the heart rate. There was no consistently significant difference between treatments with respect to blood pressure control. Differences in heart rate were more pronounced, with the reduction due to carvedilol being generally intermediate between nifedipine and atenolol. Further studies of carvedilol in hypertension, as well as other indications, are warranted.