A theoretical model for brisk walking- and running-induced lower urinary tract symptoms (BRUTS) and the development of the BRUTS-questionnaire (BRUTS-Q): A focus group and Delphi study.

AIMS: Existing questionnaires provide limited information on the nature, severity and context surrounding lower urinary tract symptoms (LUTS) experienced during running, jogging and brisk walking. The aims of this study were to develop a theoretical model of the experience of LUTS by females participating in gait-based exercise activities and to use this model to generate a questionnaire to evaluate the presence, symptoms and bother associated with LUTS experienced by females during gait-based activities. METHODS: A theoretical model was developed through a review of the literature and refined through a focus group consultation including pelvic health physiotherapists, females who experienced leakage during exercise and academic researchers who studied female LUTS. A draft questionnaire was developed using key constructs identified in the model by the focus group. A new expert panel was recruited, which included physiotherapists, women with self-reported gait-induced LUTS and urogynecologists. This panel followed a DELPHI process to evaluate the relevance and completeness of the constructs within the questionnaire. RESULTS: Two rounds of consultation were required to reach consensus on the completeness of included constructs as well as the inclusion and wording of questions. The resulting questionnaire contains questions related to five key constructs: physical activity characteristics, symptoms of urgency, urgency urinary incontinence, stress urinary incontinence experienced during exercise and management/mitigation strategies adopted by respondents. CONCLUSIONS: The content validity of the brisk walking- and running-induced lower urinary tracts symptoms questionnaire has been established. The next steps are to ensure that the questionnaire has adequate comprehensibility, followed by adequate measurement properties.

Social distancing causally impacts the spread of SARS-CoV-2: a U.S. nationwide event study.

We assess the causal impact of social distancing on the spread of SARS-CoV-2 in the U.S. using the quasi-natural experimental setting created by the spontaneous relaxation of social distancing behavior brought on by the protests that erupted across the nation following George Floyd's tragic death on May 25, 2020. Using a difference-in-difference specification and a balanced sample covering the [- 30, 30] day event window centered on the onset of protests, we document an increase of 1.34 cases per day, per 100,000 population, in the SARS-CoV-2 incidence rate in protest counties, relative to their propensity score matching non-protest counterparts. This represents a 26.8% increase in the incidence rate relative to the week preceding the protests. We find that the treatment effect only manifests itself after the onset of the protests and our placebo tests rule out the possibility that our findings are attributable to chance. Our research informs policy makers and provides insights regarding the usefulness of social distancing as an intervention to minimize the spread of SARS-CoV-2.

Stress Impairs Episodic Retrieval by Disrupting Hippocampal and Cortical Mechanisms of Remembering.

Despite decades of science investigating the neural underpinnings of episodic memory retrieval, a critical question remains: how does stress influence remembering and the neural mechanisms of recollection in humans? Here, we used functional magnetic resonance imaging and multivariate pattern analyses to examine the effects of acute stress during retrieval. We report that stress reduced the probability of recollecting the details of past experience, and that this impairment was driven, in part, by a disruption of the relationship between hippocampal activation, cortical reinstatement, and memory performance. Moreover, even memories expressed with high confidence were less accurate under stress, and this stress-induced decline in accuracy was explained by reduced posterior hippocampal engagement despite similar levels of category-level cortical reinstatement. Finally, stress degraded the relationship between the engagement of frontoparietal control networks and retrieval decision uncertainty. Collectively, these findings demonstrate the widespread consequences of acute stress on the neural systems of remembering.

Feasibility of studying the association between intraoperative regional cerebral oxygen saturation and postoperative functional decline (ReFUNCTION): a pilot sub-study of NeuroVISION-Cardiac Surgery.

PURPOSE: Function describes an individual's ability to perform everyday activities. In the context of cardiac surgery, functional changes quantify the effect of surgery on one's day-to-day life. Decreases in regional cerebral oxygen saturation (rScO2) measured using near-infrared spectroscopy (NIRS) has been associated with postoperative cognitive decline but its relationship with function has not been studied. We sought to determine the feasibility of conducting a large observational study examining the relationship between decreases in rScO2 during cardiac surgery and postoperative functional decline. METHODS: We undertook a single-centre, pilot sub-study of the NeuroVISION-Cardiac Surgery pilot study, which included adults undergoing isolated coronary artery bypass grafting on cardiopulmonary bypass; all patients enrolled in NeuroVISION-Cardiac Surgery were included. Function was evaluated at baseline, 30 days, and three months using the Standardized Assessment of Global activities in the Elderly (SAGE) scale. Blinded NIRS monitors were affixed for the duration of surgery. Our feasibility outcomes were to recruit one patient per week, obtain complete NIRS data in ≥ 90%, obtain SAGE at all time-points in ≥ 90%, and determine the time required for NIRS data to be transcribed into case report forms. RESULTS: 49/50 patients enrolled in NeuroVISION-Cardiac Surgery were recruited over 48 weeks (1.02 patients/week). Of the 49 included patients, 49 (100%) had complete NIRS data and 44 (90%) had complete SAGE data. The time required for NIRS data collection was a mean (standard deviation) of 5.5 (1.8) min per patient. CONCLUSION: This pilot study shows the feasibility of conducting a large observational study examining the relationship between decreases in cerebral saturation during cardiac surgery and postoperative functional decline. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT04241289); registered 27 January 2020.

RéSUMé: OBJECTIF : La capacité fonctionnelle constitue la capacité d'une personne à accomplir des activités quotidiennes. Dans le contexte d'une chirurgie cardiaque, les changements fonctionnels permettent de quantifier l'effet de la chirurgie sur le quotidien des individus. Les baisses de la saturation en oxygène cérébral régional (rScO2) mesurées à l'aide de la spectroscopie proche infrarouge (NIRS) ont été associées à un déclin cognitif postopératoire, mais leur relation par rapport à la capacité fonctionnelle n'a pas été étudiée. Nous avons tenté de déterminer s'il était possible de réaliser une vaste étude observationnelle examinant la relation entre les baisses de rScO2 pendant une chirurgie cardiaque et le déclin fonctionnel postopératoire. MéTHODE : Nous avons entrepris une sous-étude pilote monocentrique de l'étude pilote NeuroVISION-Cardiac Surgery, qui incluait des adultes subissant une chirurgie de pontage aortocoronarien sous circulation extracorporelle; tous les patients recrutés dans l'étude NeuroVISION-Cardiac Surgery ont été inclus dans ce volet. La capacité fonctionnelle a été évaluée avant l'opération, puis à 30 jours et trois mois à l'aide de l'échelle SAGE (Standardized Assessment of Global activities in the Elderly, soit Évaluation standardisée de la fonction globale chez la personne âgée). Des moniteurs de NIRS étaient installés pour toute la durée de la chirurgie sans que les valeurs ne soient connues de l'équipe traitante. Nos critères de faisabilité consistaient à recruter un patient par semaine, obtenir des données de NIRS complètes pour ≥ 90 % des patients, obtenir des données de SAGE pour tous les points dans le temps pour ≥ 90 % des patients, et déterminer le temps nécessaire à retranscrire les données de NIRS dans les formulaires d'étude de cas. RéSULTATS : Au total, 49/50 patients recrutés dans l'étude NeuroVISION-Cardiac Surgery ont été recrutés sur une période de 48 semaines (1,02 patients/semaine). Parmi les 49 patients inclus, les données de NIRS ont été obtenues pour 49 (100 %) patients et les données de SAGE pour 44 (90 %) patients. Le temps nécessaire à la collecte de données de NIRS était en moyenne (écart type) de 5,5 (1,8) min par patient. CONCLUSION : L'étude pilote a démontré la faisabilité d'une vaste étude observationnelle examinant la relation entre les baisses de la saturation cérébrale pendant la chirurgie cardiaque et le déclin fonctionnel postopératoire. ENREGISTREMENT DE L'éTUDE : www.clinicaltrials.gov (NCT04241289); enregistrée le 27 janvier 2020.

Cognitive focus affects spatial decisions under conditions of uncertainty.

Finding one's way to a destination is a common, everyday task that often relies on spatial information provided by humans and/or automatic devices. However, the information can be inaccurate. How we decide which route to take will depend on our thoughts about the available route information, including who or what provided it, and how these sources may be associated with differential accuracy and fallibility. In three experiments (previously reported in Brunyé et al. (Q J Exper Psychol 68(3):585-607, 2015)), we found that when route directions conflicted with the perceived environment, people trusted the landmark information other humans provided, but relied on the turn direction information from an automatic device. But what guides these behavioral results? Here we present a systematic linguistic analysis of retrospective reports that sheds some light on how information about the direction source affects cognitive focus. A focus on direction sources in the instruction triggered a cognitive focus on the direction source throughout. Participants who systematically switched strategies focused more on features of the scenario than those who did not. Non-switching strategies were associated with a higher focus on the participants' own reasoning processes, in particular when relying on turn information. These results highlight how cognitive focus is guided by scenario factors and individual preferences, triggering inferences that influence decisions.

Relationships Between 3-Dimensional Transperineal Ultrasound Imaging and Digital Intravaginal Palpation Assessments of the Pelvic Floor Muscles in Women With and Without Provoked Vestibulodynia.

BACKGROUND: Digital intravaginal palpation remains the favored method for clinical assessment of pelvic floor muscle (PFM) function in women; however, there is growing interest in using transperineal ultrasound imaging (TPUSI). TPUSI does not involve vaginal penetration, making it particularly relevant for PFM assessment in women with genito-pelvic pain and penetration disorders. AIMS: To study the relations between measures of PFM morphology and function assessed using 3-dimensional (3D) TPUSI and PFM assessment through intravaginal palpation. METHODS: 77 nulliparous premenopausal women with (n = 38) and without (n = 39) PVD participated. 3D TPUSI was used to measure levator hiatal dimensions at rest, at maximal voluntary contraction (MVC) of the PFMs, and at maximal Valsalva maneuver (MVM). Intravaginal palpation was used to assess PFM strength, PFM tone, PFM relaxation after contraction, and vaginal flexibility; each was scored using an ordinal grading scale. Ultrasound and palpation outcomes were compared using Spearman correlation coefficients and Kruskal-Wallis 1-way analyses of variance by rank. OUTCOMES: Outcomes included ultrasound measures of the levator hiatal area, anteroposterior diameter, and left-right transverse diameter at rest, at MVC, and at MVM; raw and relative changes in hiatal dimensions between rest and MVC and between rest and MVM; and palpation measures of PFM strength, tone, and relaxation after contraction, and vaginal flexibility. RESULTS: Weak to fair correlations were found between ultrasound and palpation measures. A smaller levator hiatus at rest was associated with greater PFM tone, less PFM relaxation, and less vaginal flexibility. Greater levator hiatal constriction and shortening of the hiatal anteroposterior diameter at MVC were associated with greater palpated PFM strength. Greater hiatal distention at MVM was associated with lower PFM tone and greater relaxation. CLINICAL TRANSLATION: 3D TPUSI and intravaginal palpation provide related but distinct information about PFM function in young women with and without PVD with high functioning PFMs. STRENGTHS AND LIMITATIONS: This was the first study to compare PFM assessment using 3D TPUSI and intravaginal palpation in nulliparous premenopausal women. A main strength of the study was the inclusion of women with PVD and asymptomatic controls, which provided a wide range in outcomes because differences in PFM morphology and function exist between women with and without PVD. The lack of inclusion of older women and women with weaker and/or hypotonic PFMs limits the generalizability of the findings. CONCLUSION: Although TPUSI has several advantages, including painless application, it is not recommended as a replacement for digital palpation in the clinical assessment of PFM function. Thibault-Gagnon S, Goldfinger C, Pukall C, et al. Relationships Between 3-Dimensional Transperineal Ultrasound Imaging and Digital Intravaginal Palpation Assessments of the Pelvic Floor Muscles in Women With and Without Provoked Vestibulodynia. J Sex Med 2018;15:346-360.

Differences in Pelvic Morphology Between Women With and Without Provoked Vestibulodynia.

OBJECTIVE: Pelvic morphology has been suggested to reflect increased tone and reduced strength of the pelvic floor muscles (PFMs) in women with provoked vestibulodynia (PVD) compared to healthy controls. We aimed to determine whether there are differences in pelvic morphology in the resting state, on maximum voluntary contraction (MVC), or on maximum effort Valsalva maneuver (MVM) between women with and without PVD. METHODS: While imaged using ultrasound, 38 women with PVD and 39 controls relaxed their PFMs, performed 3 MVCs and performed 3 MVMs. Levator plate length (LPL), levator plate angle (LPA), and anorectal angle (ARA) were determined at rest, at MVC and at MVM. The displacement of the bladder neck (BN) on MVC and on MVM was also determined. Two-way ANCOVAs were used to evaluate the main effects of group and task, the interaction between group and task, and the effect of resting morphology on LPL, LPA, and ARA. A 2-way repeated-measures ANOVA was used to determine whether the groups differed in terms of BN displacement during the tasks. RESULTS: Women with PVD had smaller LPLs and LPAs than controls across all tasks. The significant group differences in LPL and LPA at MVC and MVM were no longer significant once the resting values were included as covariates in the models. Bladder neck displacement differed between the groups at MVM but not at MVC. CONCLUSION: Women with PVD display shorter LPL sand smaller LPAs than controls but their behavior does not differ when MVC and MVMs are performed. Our results do not support the hypothesis that women with PVD demonstrate abnormalities in PFM contractility on MVC or compliance on MVM.

Effectiveness of Cognitive-Behavioral Therapy and Physical Therapy for Provoked Vestibulodynia: A Randomized Pilot Study.

INTRODUCTION: Non-medical and non-surgical treatments for provoked vestibulodynia target psychological, sexual, and pelvic floor muscle factors that maintain the condition. AIM: The goal of the study was to compare the effects of cognitive-behavioral therapy (CBT) and physical therapy (PT) on pain and psychosexual outcomes in women with provoked vestibulodynia. METHODS: In a clinical trial, 20 women with provoked vestibulodynia were randomly assigned to receive CBT or comprehensive PT. Participants were assessed before treatment, after treatment, and at 6-month follow-up by gynecologic examination, structured interviews, and standardized questionnaires measuring pain, psychological, and sexual variables. MAIN OUTCOME MEASURES: Outcome measurements were based on an adaptation of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations. The primary outcome was change in intercourse pain intensity. Secondary outcomes included pain during the cotton swab test, pain with various sexual and non-sexual activities, and sexual functioning and negative pain cognitions. RESULTS: The two treatment groups demonstrated significant decreases in vulvar pain during sexual intercourse, with 70% and 80% of participants in the CBT and PT groups demonstrating a moderate clinically important decrease in pain (≥30%) after treatment. Participants in the two groups also had significant improvements in pain during the gynecologic examination, the percentage of painful intercourse attempts, the percentage of activities resulting in pain, and the ability to continue intercourse without stopping because of pain. Psychological outcomes, including pain catastrophizing and perceived control over pain, also showed improvement in the two groups. Significant improvements in sexual functioning were observed only in participants who completed CBT. Few between-group differences were identified other than the PT group showing earlier improvements in some outcomes. Nearly all improvements were maintained at the 6-month follow-up. CONCLUSION: The results of the study suggest that CBT and PT can lead to clinically meaningful improvements in pain and areas of psychosexual functioning.

Differences in the Biometry of the Levator Hiatus at Rest, During Contraction, and During Valsalva Maneuver Between Women With and Without Provoked Vestibulodynia Assessed by Transperineal Ultrasound Imaging.

INTRODUCTION: Pelvic floor muscle (PFM) involvement is suspected in the pathophysiology of provoked vestibulodynia (PVD); however, the underlying mechanisms are unclear. PFM morphology can be inferred from the biometry of the levator hiatus determined through dynamic ultrasound imaging. AIMS: The aim of this study was to determine the nature of PFM involvement in women with PVD via an evaluation of the biometry of the levator hiatus at rest, upon maximal voluntary contraction (MVC) of the PFMs, and upon maximal Valsalva maneuver (MVM). METHODS: Thirty-eight women with PVD and 39 asymptomatic controls were imaged using 3D transperineal ultrasound. Levator hiatal dimensions (area; left-right [LR] and anteroposterior [AP] diameters) were measured at rest, on MVC, and on MVM. Differences in hiatal dimensions and in relative changes in dimensions from rest to MVC and from rest to MVM were compared between groups using separate 1-way analyses of variance for each measure and task. Analysis of covariance models were used to investigate the impact of levator hiatal dimensions at rest on the relative changes in the levator hiatal dimensions during MVC and MVM. MAIN OUTCOME MEASURES: Levator hiatal area, LR, and AP diameters, at rest, on MVC, and on MVM were the main outcome measures. Relative changes in hiatal dimensions were assessed as the percent change in hiatal area, LR diameter, and AP diameter. RESULTS: In comparison with controls, women with PVD had smaller hiatal areas at rest, on MVC, and on MVM, concurrent with smaller LR diameters on MVM. Women with PVD had a significantly smaller change in hiatal area on MVM than controls, but no differences were evident on MVC. In both groups, smaller levator hiatal dimensions at rest were associated with smaller relative decreases in dimensions on MVC and larger relative increases in dimensions on MVM. CONCLUSION: In comparison to controls, women with PVD appear to have narrower levator hiatus' and less capacity to distend their hiatus on Valsalva. The state of the PFMs at rest appears to significantly influence biometric changes in the PFMs during contraction and Valsalva.

Active and Passive Components of Pelvic Floor Muscle Tone in Women with Provoked Vestibulodynia: A Perspective Based on a Review of the Literature.

AIM: Pelvic floor muscle (PFM) dysfunctions, especially elevated tone or tension, are suggested to play an important role in the pathophysiology of provoked vestibulodynia (PVD). However, the involvement of the PFMs remains misunderstood as the assessment of muscle tone is complex and requires a thorough understanding of muscle physiology in relation to the characteristics and limitations of current PFM assessment tools. The aim of this review was to describe the structures and mechanisms involved in muscle tone in normally innervated muscle, and to discuss and relate these concepts to the PFM findings in women with PVD. METHODS: A narrative overview of the literature retrieved from searches of electronic databases and hand searches. RESULTS: Muscle tone in a normally innervated muscle comprises both active (contractile) and passive (viscoelastic) components. Current methods for evaluating PFM tone such as digital palpation, ultrasound imaging, pressure perineometry, dynamometry, and electromyography may evaluate different components. Research findings suggestive of PFM hypertonicity in women with PVD include elevated general PFM tone, changes in viscoelastic properties, and at least in some women, abnormal increases in electrogenic activity. CONCLUSION: There is a growing body of evidence to support the involvement of PFM hypertonicity in the pathophysiology of PVD. Limitations of the instruments as well as their properties should be considered when evaluating PFM tone in order to obtain better insight into which component of PFM tone is assessed. Future research is required for further investigating the underlying mechanisms of PFM hypertonicity, and studying the specific effects of physiotherapeutic interventions on PFM tone in women with PVD.

Do women notice the impact of childbirth-related levator trauma on pelvic floor and sexual function? Results of an observational ultrasound study.

INTRODUCTION AND HYPOTHESIS: The levator ani is thought to play an important role in sexual function; however, to date little literature has been published on the impact of delivery-related levator trauma on female sexual function. We hypothesised that delivery-related levator trauma has a negative impact on women's reports of pelvic floor and sexual function postpartum. METHODS: In 294 primigravid women with a singleton pregnancy, four-dimensional (4D) translabial ultrasound imaging was used to assess delivery-related levator avulsion and levator hiatal over-distension, and postpartum pelvic floor and sexual function was assessed by an in-house validated questionnaire. Associations between questionnaire responses and levator avulsion and hiatal over-distension were investigated using standard linear modelling methods. RESULTS: Levator avulsion was diagnosed in 14% of women (42 out of 292; 25 unilateral, 17 bilateral) and was found to be significantly associated with lower scores for the pelvic floor integrity and function domain of the questionnaire (P < 0.0005). Avulsion was associated with lower scores for this domain (no avulsion = 2.78, unilateral avulsion = 2.61, bilateral avulsion = 2.29). This association remained significant after controlling for potential confounders (p = 0.013). Avulsion was not associated with any of the other domains of sexual function and levator hiatal over-distension was not associated with scores for any of the questionnaire domains. CONCLUSIONS: The effect of levator avulsion on pelvic floor and sexual function an average of 5.2 months after childbirth seems to be limited to a perception of increased vaginal and pelvic floor muscle laxity, and reduced pelvic floor muscle efficiency. The impact of levator hiatal over-distension on postpartum pelvic floor and sexual function appears to be negligible.

Extracellular vesicles may provide an alternative detoxification pathway during skeletal muscle myoblast ageing.

Skeletal muscle (SM) acts as a secretory organ, capable of releasing myokines and extracellular vesicles (SM-EVs) that impact myogenesis and homeostasis. While age-related changes have been previously reported in murine SM-EVs, no study has comprehensively profiled SM-EV in human models. To this end, we provide the first comprehensive comparison of SM-EVs from young and old human primary skeletal muscle cells (HPMCs) to map changes associated with SM ageing. HPMCs, isolated from young (24 ± 1.7 years old) and older (69 ± 2.6 years old) participants, were immunomagnetically sorted based on the presence of the myogenic marker CD56 (N-CAM) and cultured as pure (100% CD56+) or mixed populations (MP: 90% CD56+). SM-EVs were isolated using an optimised protocol combining ultrafiltration and size exclusion chromatography (UF + SEC) and their biological content was extensively characterised using Raman spectroscopy (RS) and liquid chromatography mass spectrometry (LC-MS). Minimal variations in basic EV parameters (particle number, size, protein markers) were observed between young and old populations. However, biochemical fingerprinting by RS highlighted increased protein (amide I), lipid (phospholipids and phosphatidylcholine) and hypoxanthine signatures for older SM-EVs. Through LC-MS, we identified 84 shared proteins with functions principally related to cell homeostasis, muscle maintenance and transcriptional regulation. Significantly, SM-EVs from older participants were comparatively enriched in proteins involved in oxidative stress and DNA/RNA mutagenesis, such as E3 ubiquitin-protein ligase TTC3 (TTC3), little elongation complex subunit 1 (ICE1) and Acetyl-CoA carboxylase 1 (ACACA). These data suggest SM-EVs could provide an alternative pathway for homeostasis and detoxification during SM ageing.

Management of female sexual pain disorders.

Our understanding of the sexual pain disorders vaginismus and dyspareunia has been fundamentally altered over the past two decades due to increased attention and empirically sound research in this domain. This increased knowledge base has included a shift from a dualistic view of the etiology of painful and/or difficult vaginal penetration being due to either psychological or physiological causes, to a multifactorial perspective. The present chapter reviews current classification and prevalence rates, including ongoing definitional debates. Research regarding the etiology, assessment and management of sexual pain disorders is discussed from a biopsychosocial perspective. Cyclical theories of the development and maintenance of sexual pain disorders, which highlight the complex interplay among physiological, psychological and social factors, are described. Medical/surgical treatment options, pelvic floor rehabilitation and psychological approaches are reviewed, as well as future directions in treatment research.

Off-label use of drug-eluting versus bare metal stents: a lesion-specific systematic review of long-term outcomes.

OBJECTIVE: The purpose of this systematic review was to evaluate differences in lesion-specific outcomes with the "off-label" use of drug-eluting stents (DES) versus bare metal stents (BMS). METHODS: MEDLINE, PubMed, the Cochrane databases, and other Web were searched for studies evaluating off-label use of DES and BMS with the same characteristics. Of 1,258 abstracts or manuscripts reviewed, 112 studies were included (total N = 23,438). Studies were excluded if patients received both types of stent or no stent; lesion type was unknown; lesion-specific outcomes for ≥6 months were unavailable; or <25 patients were enrolled. RESULTS: Overall mortality at 6-12 months was approximately 3% for BMS and DES for off-label use. Increase in mortality was greater from 6-12 months to 2 years with BMS than with DES (3.3%-9.1%; 2.8%-4.1%); however, rates were similar at 3 years (BMS: 18.8%; DES:15.3%). Myocardial Infarction rates were similar for both types at 6-12 months (BMS: 6.5%; DES: 6.0%). Overall rates of stent thrombosis were 1.8% and 1.7% for BMS and DES, respectively. Similar or slightly lower rates of stent thrombosis were seen for most lesion types, except higher rates for small vessels for BMS (5.2%) and true bifurcation for DES (3.3%). Rates of target lesion revascularization (TLR) were 7.5% for BMS and 19.6% for DES at 6-12 months. At 2-years TLR remained lower than DES. When the combined group was compared to registry data alone, similar values were seen. CONCLUSIONS: Rates of mortality, myocardial infarction (MI), and stent thrombosis were similar in patients receiving BMS or DES, while TLR rates were lower in DES patients.

Stress Disrupts Human Hippocampal-Prefrontal Function during Prospective Spatial Navigation and Hinders Flexible Behavior.

The ability to anticipate and flexibly plan for the future is critical for achieving goal-directed outcomes. Extant data suggest that neural and cognitive stress mechanisms may disrupt memory retrieval and restrict prospective planning, with deleterious impacts on behavior. Here, we examined whether and how acute psychological stress influences goal-directed navigational planning and efficient, flexible behavior. Our methods combined fMRI, neuroendocrinology, and machine learning with a virtual navigation planning task. Human participants were trained to navigate familiar paths in virtual environments and then (concurrent with fMRI) performed a planning and navigation task that could be most efficiently solved by taking novel shortcut paths. Strikingly, relative to non-stressed control participants, participants who performed the planning task under experimentally induced acute psychological stress demonstrated (1) disrupted neural activity critical for mnemonic retrieval and mental simulation and (2) reduced traversal of shortcuts and greater reliance on familiar paths. These neural and behavioral changes under psychological stress were tied to evidence for disrupted neural replay of memory for future locations in the spatial environment, providing mechanistic insight into why and how stress can alter planning and foster inefficient behavior.

Perioperative covert stroke in patients undergoing coronary artery bypass graft surgery.

Objectives: Covert stroke is a complication of coronary artery bypass graft surgery that is increasingly recognized as a serious problem. In noncardiac surgery settings, covert stroke is associated with the development of delirium, long-term cognitive decline, and future clinical stroke. Therefore, we sought to determine the feasibility of conducting a large, prospective cohort study of the influence of covert stroke on neurocognitive outcomes in patients undergoing coronary artery bypass graft surgery. Methods: NeuroVISION Cardiac pilot was a prospective cohort study enrolling patients aged ≥21 years undergoing isolated coronary artery bypass graft surgery to receive diffusion-weighted magnetic resonance imaging of the brain after surgery to identify patients with covert stroke. Patients were screened for postoperative delirium in-hospital and were administered questionnaires of cognitive and global function (once before and twice after surgery). Regional cerebral oxygen saturation was recorded during surgery using near-infrared spectroscopy. Results: Between March 27, 2017, and February 11, 2018, 50 of 66 patients enrolled (76%) completed the brain magnetic resonance imaging (1 patient per week). Among the 49 patients included in the analysis, 19 (39%; 95% confidence interval, 26%-53%) experienced perioperative covert stroke and 3 (6%) had a clinical stroke within 30 days of surgery. Postoperative delirium occurred in 5 (26%) patients with covert stroke and in 3 (10%) patients who did not experience covert stroke. Conclusions: The NeuroVISION Cardiac pilot study established the feasibility of conducting a large, prospective cohort study of the determinants and consequences of covert stroke in patients undergoing coronary artery bypass graft surgery.

Content Tuning in the Medial Temporal Lobe Cortex: Voxels that Perceive, Retrieve.

How do we recall vivid details from our past based only on sparse cues? Research suggests that the phenomenological reinstatement of past experiences is accompanied by neural reinstatement of the original percept. This process critically depends on the medial temporal lobe (MTL). Within the MTL, perirhinal cortex (PRC) and parahippocampal cortex (PHC) are thought to support encoding and recall of objects and scenes, respectively, with the hippocampus (HC) serving as a content-independent hub. If the fidelity of recall indeed arises from neural reinstatement of perceptual activity, then successful recall should preferentially draw upon those neural populations within content-sensitive MTL cortex that are tuned to the same content during perception. We tested this hypothesis by having eighteen human participants undergo functional MRI (fMRI) while they encoded and recalled objects and scenes paired with words. Critically, recall was cued with the words only. While HC distinguished successful from unsuccessful recall of both objects and scenes, PRC and PHC were preferentially engaged during successful versus unsuccessful object and scene recall, respectively. Importantly, within PRC and PHC, this content-sensitive recall was predicted by content tuning during perception: Across PRC voxels, we observed a positive relationship between object tuning during perception and successful object recall, while across PHC voxels, we observed a positive relationship between scene tuning during perception and successful scene recall. Our results thus highlight content-based roles of MTL cortical regions for episodic memory and reveal a direct mapping between content-specific tuning during perception and successful recall.

The temporal relationship between activity of the pelvic floor muscles and motion of selected urogenital landmarks in healthy nulliparous women.

AIMS: The purpose of this study was to investigate the relationship between pelvic floor muscle (PFM) electromyographic (EMG) activation and urogenital landmark motion measured using 2D transperineal ultrasound (US) imaging. METHODS: Eight healthy, nulliparous women performed maximum voluntary PFM contractions while EMG and transperineal US images were acquired simultaneously. Changes in the levator plate length (LPL), bladder neck (BN) position and urethral position were determined by visual inspection. The relative timing of EMG onset and the onset of landmark motion, and the correlation coefficients between EMG activation and landmark motion were computed. Comparisons between the correlation coefficients and onset latencies of each landmark motion were made using one-way analysis of variance models. RESULTS: Despite generally good reliability metrics for the onset of EMG and the onset of landmark motion, the relative timing of EMG onset and the onset of landmark motion demonstrated no systematic patterns of activation onset. That said, the overall motion of the different urogenital landmarks throughout the MVC task was highly correlated with the PFM EMG data; correlation coefficients were generally good (>0.90) and highly significant (p < .001). The correlation between PFM EMG and LPL motion was significantly better than the correlation between PFM EMG and motion of the other landmarks. The relevance of one outlier is discussed. CONCLUSIONS: The motion of all urogenital landmarks seen on US imaging is highly correlated with PFM EMG activation during maximum voluntary PFM contractions and may therefore be of value in the context of biofeedback training to infer that PFM activation has occurred. The motion of the BN, however, may require more cautious interpretation than the reduction of LPL. The timing of the onset of urogenital landmark motion on transperineal US imaging does not precede nor follow the timing of PFM activation, while the high variance of relative onset timing makes the onset of landmark motion of questionable value when training or evaluating co-ordination or motor control.

Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults.

Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.5 ± 0.6 kg/m2 ) and 8 obese (33.6 ± 1.2 kg/m2 ) physically active young adults participated in a study that determined muscle protein synthesis and intracellular signaling at rest and following an acute bout of resistance exercise. Mixed muscle protein synthesis was determined by combining stable isotope tracer ([13 C6 ]phenylalanine) infusion with serial biopsies of the vastus lateralis. A unilateral leg resistance exercise model was adopted so that resting and postexercise measurements of muscle protein synthesis could be obtained simultaneously. Obesity was associated with higher basal levels of serum insulin (P < 0.05), plasma triacylglycerol (P < 0.01), plasma cholesterol (P < 0.01), and plasma CRP (P < 0.01), as well as increased insulin resistance determined by HOMA-IR (P < 0.05). However, resting and postexercise rates of muscle protein synthesis were not significantly different between lean and obese participants (P = 0.644). Furthermore, resistance exercise stimulated muscle protein synthesis (~50% increase) in both groups (P < 0.001), with no difference between lean and obese (P = 0.809). Temporal increases in the phosphorylation of intracellular signaling proteins (AKT/4EBP1/p70S6K) were observed within the exercised leg (P < 0.05), with no differences between lean and obese. These findings suggest a normal anabolic response to muscle loading in obese young adults.

Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells and prevents neutrophil adhesion: an ERalpha-mediated pathway.

OBJECTIVE: Interferon gamma (IFN-gamma) was shown to induce CD40 and CD40L expression on endothelial cells (ECs) and consequently to promote neutrophil adhesion. The pro- and anti-inflammatory effects of estrogens are well recognized but their role on the regulation of CD40 and CD40L expression on ECs remains undefined. METHODS AND RESULTS: Treatment of porcine aortic endothelial cells (PAEC) with IFN-gamma for 24 h enhanced CD40 and CD40L expression by 97% and 78%, respectively. Pretreatment of PAEC with 17-beta-estradiol (17betaE) for 24 h prevented the latter expression of CD40/CD40L. Treatment of PAEC with antisense oligomers targeting ERalpha mRNA attenuated the ability of 17betaE to inhibit the IFN-gamma-induced CD40 and CD40L protein expression. The IFN-gamma activation pathway of CD40 is known to involve the phosphorylation of the Janus activated kinase (JAK) and the signal transducer and activator of transcription 1 (Stat1). 17betaE, acting via the estrogen receptor alpha (ERalpha), abrogated IFN-gamma-mediated effects on Stat1 but failed to inhibit Jak1 and Jak2 phosphorylation. Furthermore, 17betaE prevented neutrophil adhesion induced by IFN-gamma. CONCLUSION: In summary, 17betaE binding to ERalpha blocked IFN-gamma-induced Stat1 phosphorylation, CD40 and CD40L protein expression, and neutrophil adhesion onto ECs.