Sex differences in the physiological responses to cardiac rehabilitation: a systematic review.

BACKGROUND: Heart disease is one of the leading causes of death in Canada. Many heart disease patients are referred for cardiac rehabilitation, a multidisciplinary outpatient program often consisting of exercise training. Cardiac rehabilitation has been proven to be a successful secondary preventative measure in reducing mortality and improving overall health in heart disease patients, and its completion is important for both sexes as there is growing evidence that women benefit as much as men, if not more, with regard to mortality. It is important to note that previous studies have shown that healthy men and women respond differently to aerobic and resistance training, possibly due to hormones, body composition, autonomic and/or cardiovascular differences. However, evaluating sex differences in the efficacy of standard cardiac rehabilitation programs has not yet been fully explored with many studies investigating clinical or anthropometric data but not physiological outcomes. This systematic review aimed to investigate physiological differences in male and female heart disease patients after cardiac rehabilitation. The inclusion criteria were purposefully broad to encompass many cardiac rehabilitation scenarios, many cardiac disease states, and various program lengths and intensities with the intention of highlighting strengths and weaknesses of the current body of literature. METHODS: To conduct a synthesis without meta-analysis, a search strategy was generated to examine the relationships between heart disease patients, a supervised exercise program, physiological outcomes, and sex differences. The review was registered (Prospero: CRD42021251614) and the following databases were searched from inception to 19 December 2023: APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), Embase (Ovid), Emcare Nursing (Ovid), Medline All (Ovid; includes PubMed non-Medline), and Web of Science Core Collection. Eighty-eight studies pertaining to fitness, metabolism, body composition, respiratory function, cardiac function and C-reactive protein underwent data extraction. RESULTS AND CONCLUSIONS: Importantly, this review suggests that men and women respond similarly to a wide-range of cardiac rehabilitation programs in most physiological variables. However, many studies discussing maximal oxygen consumption, functional capacity, six-minute walk distances, and grip strength suggest that men benefit more. Further research is required to address certain limitations, such as appropriate statistical methods and type/intensity of exercise interventions.

The effects of oral contraceptives on resting autonomic function and the autonomic response to physiological stressors: a systematic review.

PURPOSE: This systematic review aimed to summarize how oral contraceptives (OC) affect resting autonomic function and the autonomic response to a variety of physiological stressors. METHODS: A search strategy was created to retrieve citations investigating physiological responses comparing OC users to non-users (NOC) in response to autonomic reflex activation. RESULTS: A total of 6148 citations were identified across databases from inception to June 2, 2022, and 3870 citations were screened at the abstract level after deduplication. Then, 133 texts were assessed at full-text level, and only 40 studies met eligibility requirements. Included citations were grouped by the aspect of autonomic function assessed, including autonomic reflex (i.e., baroreflex, chemoreflex, mechanoreflex, metaboreflex, and venoarterial reflex), or indicators (i.e., heart rate variability, pulse wave velocity, and sympathetic electrodermal activity), and physiological stressors that may alter autonomic function (i.e., auditory, exercise, mental or orthostatic stress, altitude, cold pressor test, sweat test, and vasodilatory infusions). CONCLUSION: OC influence the physiological responses to chemoreflex, mechanoreflex, and metaboreflex activation. In terms of autonomic indices and physiological stressors, there are more inconsistencies within the OC literature, which may be due to estrogen dosage within the OC formulation (i.e., heart rate variability) or the intensity of the stressor (exercise intensity/duration or orthostatic stress). Further research is required to elucidate the effects of OC on these aspects of autonomic function because of the relatively small amount of available research. Furthermore, researchers should more clearly define or stratify OC use by duration, dose, and/or hormone cycling to further elucidate the effects of OC.

Interchange reconnection as the source of the fast solar wind within coronal holes.

The fast solar wind that fills the heliosphere originates from deep within regions of open magnetic field on the Sun called 'coronal holes'. The energy source responsible for accelerating the plasma is widely debated; however, there is evidence that it is ultimately magnetic in nature, with candidate mechanisms including wave heating1,2 and interchange reconnection3-5. The coronal magnetic field near the solar surface is structured on scales associated with 'supergranulation' convection cells, whereby descending flows create intense fields. The energy density in these 'network' magnetic field bundles is a candidate energy source for the wind. Here we report measurements of fast solar wind streams from the Parker Solar Probe (PSP) spacecraft6 that provide strong evidence for the interchange reconnection mechanism. We show that the supergranulation structure at the coronal base remains imprinted in the near-Sun solar wind, resulting in asymmetric patches of magnetic 'switchbacks'7,8 and bursty wind streams with power-law-like energetic ion spectra to beyond 100 keV. Computer simulations of interchange reconnection support key features of the observations, including the ion spectra. Important characteristics of interchange reconnection in the low corona are inferred from the data, including that the reconnection is collisionless and that the energy release rate is sufficient to power the fast wind. In this scenario, magnetic reconnection is continuous and the wind is driven by both the resulting plasma pressure and the radial Alfvénic flow bursts.

The mismatch of narratives and local ecologies in the everyday governance of water access and mosquito control in an urbanizing community.

Mosquito-borne disease presents a significant threat to urban populations, but risk can be uneven across a city due to underlying environmental patterns. Urban residents rely on social and economic processes to control the environment and mediate disease risk, a phenomenon known as everyday governance. We studied how households employed everyday governance of urban infrastructure relevant to mosquito-borne disease in Bengaluru, India to examine if and how inequalities in everyday governance manifest in differences in mosquito control. We found that governance mechanisms differed for water access and mosquitoes. Economic and social capital served different roles for each, influenced by global narratives of water and vector control.

MultipleXed Population Selection and Enrichment single nucleus RNA sequencing (XPoSE-seq) enables sample identity retention during transcriptional profiling of rare populations.

Single nucleus RNA-sequencing is critical in deciphering tissue heterogeneity and identifying rare populations. However, current high throughput techniques are not optimized for rare target populations and require tradeoffs in design due to feasibility. We provide a novel snRNA pipeline, MulipleXed Population Selection and Enrichment snRNA-sequencing (XPoSE-seq), to enable targeted snRNA-seq experiments and in-depth transcriptomic characterization of rare target populations while retaining individual sample identity.

Impact of 12 weeks of basic military training on testosterone and cortisol responses.

INTRODUCTION: Military personnel train and operate in challenging multistressor environments, which can affect hormonal levels, and subsequently compromise performance and recovery. The aims of this project were to evaluate concentrations of cortisol and testosterone and subjective perceptions of stress and recovery across basic military training (BMT). METHODS: 32 male recruits undergoing BMT were tracked over a 12-week course. Saliva samples were collected weekly, on waking, 30 min postwaking and bedtime. Perceptions of stress and recovery were collected weekly. Daily physical activity (steps) were measured via wrist-mounted accelerometers across BMT. Physical fitness was assessed via the multistage fitness test and push-ups in weeks 2 and 8. RESULTS: Concentrations of testosterone and cortisol, and the testosterone:cortisol ratio changed significantly across BMT, with variations in responses concurrent with programmatic demands. Perceptions of stress and recovery also fluctuated according to training elements. Recruits averaged 17 027 steps per day between weeks 2 and 12, with week-to-week variations. On average, recruits significantly increased predicted VO2max (3.6 (95% CI 1.0 to 6.1) mL/kg/min) and push-ups (5. 5 (95% CI 1.4 to 9.7) repetitions) between weeks 2 and 8. CONCLUSIONS: Recruit stress responses oscillated over BMT in line with programmatic demands indicating that BMT was, at a group level, well-tolerated with no signs of enduring physiological strain or overtraining. The sensitivity of cortisol, testosterone and the testosterone:cortisol ratio to the stressors of military training, suggest they may have a role in monitoring physiological strain in military personnel. Subjective measures may also have utility within a monitoring framework to help ensure adaptive, rather than maladaptive (eg, injury, attrition), outcomes in military recruits.

Parker Solar Probe Observations of Solar Wind Energetic Proton Beams Produced by Magnetic Reconnection in the Near-Sun Heliospheric Current Sheet.

We report observations of reconnection exhausts in the Heliospheric Current Sheet (HCS) during Parker Solar Probe Encounters 08 and 07, at 16 R s and 20 R s , respectively. Heliospheric current sheet (HCS) reconnection accelerated protons to almost twice the solar wind speed and increased the proton core energy by a factor of ∼3, due to the Alfvén speed being comparable to the solar wind flow speed at these near-Sun distances. Furthermore, protons were energized to super-thermal energies. During E08, energized protons were found to have leaked out of the exhaust along separatrix field lines, appearing as field-aligned energetic proton beams in a broad region outside the HCS. Concurrent dropouts of strahl electrons, indicating disconnection from the Sun, provide further evidence for the HCS being the source of the beams. Around the HCS in E07, there were also proton beams but without electron strahl dropouts, indicating that their origin was not the local HCS reconnection exhaust.

Direct observations of anomalous resistivity and diffusion in collisionless plasma.

Coulomb collisions provide plasma resistivity and diffusion but in many low-density astrophysical plasmas such collisions between particles are extremely rare. Scattering of particles by electromagnetic waves can lower the plasma conductivity. Such anomalous resistivity due to wave-particle interactions could be crucial to many processes, including magnetic reconnection. It has been suggested that waves provide both diffusion and resistivity, which can support the reconnection electric field, but this requires direct observation to confirm. Here, we directly quantify anomalous resistivity, viscosity, and cross-field electron diffusion associated with lower hybrid waves using measurements from the four Magnetospheric Multiscale (MMS) spacecraft. We show that anomalous resistivity is approximately balanced by anomalous viscosity, and thus the waves do not contribute to the reconnection electric field. However, the waves do produce an anomalous electron drift and diffusion across the current layer associated with magnetic reconnection. This leads to relaxation of density gradients at timescales of order the ion cyclotron period, and hence modifies the reconnection process.

Correlation of fetal ventricular size and need for postnatal cerebrospinal fluid diversion surgery in open spina bifida.

OBJECTIVES: Open spina bifida is a common cause of hydrocephalus in the postnatal period. In-utero closure of the fetal spinal defect decreases the need for postnatal cerebrospinal fluid (CSF) diversion surgery. Good prenatal predictors of the need for postnatal CSF diversion surgery are currently lacking. In this study, we aimed to assess the association of fetal ventriculomegaly and its progression over the course of pregnancy with the rate of postnatal hydrocephalus requiring intervention. METHODS: In this retrospective study, fetuses with a prenatal diagnosis of open spina bifida were assessed longitudinally. Ventricular diameter, as well as other potential predictors of the need for postnatal CSF diversion surgery, were compared between fetuses undergoing prenatal closure and those undergoing postnatal repair. RESULTS: The diameter of the lateral ventricle increased significantly throughout gestation in both groups, but there was no difference in maximum ventricular diameter at first or last assessment between fetuses undergoing prenatal closure and those undergoing postnatal repair. There was no significant difference in the rate of progression of ventriculomegaly between the two groups, with a mean progression rate of 0.83 ± 0.5 mm/week in the prenatal-repair group and 0.6 ± 0.6 mm/week in the postnatal-repair group (P = 0.098). Fetal repair of open spina bifida was associated with a lower rate of postnatal CSF diversion surgery (P < 0.001). In all subjects, regardless of whether they had prenatal or postnatal surgery, the severity of ventriculomegaly at first and last assessments was associated independently with the need for postnatal CSF diversion surgery (P = 0.005 and P = 0.001, respectively), with a greater need for surgery in fetuses with larger ventricular size, even after controlling for gestational age at assessment. CONCLUSIONS: In fetuses with open spina bifida, fetal ventricular size increases regardless of whether spina bifida closure is performed prenatally or postnatally, but the need for CSF diversion surgery is significantly lower in those undergoing prenatal repair. Ventriculomegaly is associated independently with the need for postnatal CSF diversion in fetuses with open spina bifida, irrespective of timing of closure. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Hydrologic and soil properties of mature bioretention cells in Ontario, Canada.

Bioretention systems, which mimic natural hydrology and reduce volume of stormwater runoff, are a preferred solution for meeting water balance objectives, but lack of knowledge about the long-term performance of these systems hinders their wider adoption. This study was a field survey of mature (>3 years and up to 10 years post-construction) bioretention cells across Ontario, Canada. The survey involved visual inspections, determination of soil physical parameters and soil-water interaction parameters, infiltration capacity testing and synthetic drawdown testing. Results indicate that infiltration capacity remains above the recommended minimum of 25 mm/hr, likely due to high content soils and development of soil structure due to biological factors over time. The drawdown times for three sites ranged from 5 minutes to 6 hours, much less than the maximum allowed drawdown time of 24-48 hours. Ksat (saturated hydraulic conductivity) was only moderately negatively correlated with age, and where data existed on KSat at the beginning of operation, KSat improved for six out of nine sites. Soil-water interaction properties more closely resembled loam soils than sandy soils, which may be due to the development of a soil structure over time. We recommend conducting visual inspections regularly over infiltration capacity testing for quick determination of maintenance needs.

Faster Form of Electron Magnetic Reconnection with a Finite Length X-Line.

Observations in Earth's turbulent magnetosheath downstream of a quasiparallel bow shock reveal a prevalence of electron-scale current sheets favorable for electron-only reconnection where ions are not coupled to the reconnecting magnetic fields. In small-scale turbulence, magnetic structures associated with intense current sheets are limited in all dimensions. And since the coupling of ions are constrained by a minimum length scale, the dynamics of electron reconnection is likely to be 3D. Here, both 2D and 3D kinetic particle-in-cell simulations are used to investigate electron-only reconnection, focusing on the reconnection rate and associated electron flows. A new form of 3D electron-only reconnection spontaneously develops where the magnetic X-line is localized in the out-of-plane (z) direction. The consequence is an enhancement of the reconnection rate compared with two dimensions, which results from differential mass flux out of the diffusion region along z, enabling a faster inflow velocity and thus a larger reconnection rate. This outflow along z is due to the magnetic tension force in z just as the conventional exhaust tension force, allowing particles to leave the diffusion region efficiently along z unlike the 2D configuration.

Targeting monoamine oxidase A for T cell-based cancer immunotherapy.

Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain, where it breaks down neurotransmitters and thereby influences mood and behavior. Small-molecule MAO inhibitors (MAOIs) have been developed and are clinically used for treating depression and other neurological disorders. However, the involvement of MAO-A in antitumor immunity has not been reported. Here, we observed induction of the Maoa gene in tumor-infiltrating immune cells. Maoa knockout mice exhibited enhanced antitumor T cell immunity and suppressed tumor growth. MAOI treatment significantly suppressed tumor growth in preclinical mouse syngeneic and human xenograft tumor models in a T cell-dependent manner. Combining MAOI and anti-PD-1 treatments generated synergistic tumor suppression effects. Clinical data correlation studies associated intratumoral MAOA expression with T cell dysfunction and decreased patient survival in a broad range of cancers. We further demonstrated that MAO-A restrains antitumor T cell immunity through controlling intratumoral T cell autocrine serotonin signaling. Together, these data identify MAO-A as an immune checkpoint and support repurposing MAOI antidepressants for cancer immunotherapy.

Electron Acceleration during Macroscale Magnetic Reconnection.

The first self-consistent simulations of electron acceleration during magnetic reconnection in a macroscale system are presented. Consistent with solar flare observations, the spectra of energetic electrons take the form of power laws that extend more than two decades in energy. The drive mechanism for these nonthermal electrons is Fermi reflection in growing and merging magnetic flux ropes. A strong guide field suppresses the production of nonthermal electrons by weakening the Fermi drive mechanism. For a weak guide field the total energy content of nonthermal electrons dominates that of the hot thermal electrons even though their number density remains small. Our results are benchmarked with the hard x-ray, radio, and extreme ultraviolet observations of the X8.2-class solar flare on September 10, 2017.

Lower-Hybrid Drift Waves Driving Electron Nongyrotropic Heating and Vortical Flows in a Magnetic Reconnection Layer.

We report measurements of lower-hybrid drift waves driving electron heating and vortical flows in an electron-scale reconnection layer under a guide field. Electrons accelerated by the electrostatic potential of the waves exhibit perpendicular and nongyrotropic heating. The vortical flows generate magnetic field perturbations comparable to the guide field magnitude. The measurements reveal a new regime of electron-wave interaction and how this interaction modifies the electron dynamics in the reconnection layer.

Energy Flux Densities near the Electron Dissipation Region in Asymmetric Magnetopause Reconnection.

Magnetic reconnection is of fundamental importance to plasmas because of its role in releasing and repartitioning stored magnetic energy. Previous results suggest that this energy is predominantly released as ion enthalpy flux along the reconnection outflow. Using Magnetospheric Multiscale data we find the existence of very significant electron energy flux densities in the vicinity of the magnetopause electron dissipation region, orthogonal to the ion energy outflow. These may significantly impact models of electron transport, wave generation, and particle acceleration.

Highly structured slow solar wind emerging from an equatorial coronal hole.

During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvénic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfvén-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvénic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind.

Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.

In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vß repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.

Creatine uptake regulates CD8 T cell antitumor immunity.

T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a CrT (Slc6a8) gene, which encodes a surface transporter controlling the uptake of creatine into a cell. Using CrT knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy. We further demonstrated that creatine acts as a "molecular battery" conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell-based cancer immunotherapies.

Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.

Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patient's lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.

Publisher Correction: Electron magnetic reconnection without ion coupling in Earth's turbulent magnetosheath.

Change history: In this Letter, the y-axis values in Fig. 3f should go from 4 to -8 (rather than from 4 to -4), the y-axis values in Fig. 3h should appear next to the major tick marks (rather than the minor ticks), and in Fig. 1b, the arrows at the top and bottom of the electron-scale current sheet were going in the wrong direction; these errors have been corrected online.