Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury

Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy+total-body cooling (n=26), hypoxic-ischemic encephalopathy (n=12), acute ischemic stroke (n=15), and transient tachypnea of the newborn (n=48) was conducted; transient tachypnea of the newborn neonates were used as the control group. Absolute neutrophil count and absolute lymphocyte count at three time-intervals (0–12, 12–36, and 36–60 h after birth) were collected, and neutrophilto-lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy+total-body cooling neonates demonstrated significant time-interval-dependent changes in absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to transient tachypnea of the newborn and acute ischemic stroke patients. Pooled analysis of absolute lymphocyte count for neonates with acute ischemic stroke and hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy+total-body cooling) revealed that absolute lymphocyte count changes occurring at 0–12h are likely due to disease progression, rather than total-body cooling treatment. Conclusion: These data suggest that the neutrophil/lymphocyte response is modulated following neonatal ischemic brain injury, representing a possible target for therapeutic intervention. However, initial severity of hypoxic-ischemic encephalopathy among these patients could also account for the observed changes in the immune response to injury. Thus, additional work to clarify the contributions of cooling therapy and disease severity to neutrophil/lymphocyte response following hypoxicischemic encephalopathy in neonates is warranted

Locomotor effects of a low-frequency fire alarm on C57BL/6 male mice: a preliminary study

Maintaining appropriate acoustic conditions for animal welfare and data collection are crucial in biomedical research facilities. Negative impacts of disruptive sound are known and can include auditory damage, immune function changes, and behavioral alterations. One type of disruptive sound occurring in research facilities is that of fire alarms. To ameliorate this problem, many facilities have incorporated the use of low-frequency fire alarms that emit tones outside the rodent audible range. The impact of these devices has been assumed to be negligible. However, this has yet to be evaluated with controlled behavioral experiments. Thus, our objective was to investigate the impact of low-frequency fire alarm exposure on locomotor behavior in the open field, a test sensitive to acoustic stimuli disruption. Male mice were randomized to three alarm exposure groups (No-Alarm; Alarm-During; and Alarm-After) and placed in individual photobeam-activated locomotor chambers. The Alarm-During group displayed significantly reduced horizontal locomotion, with a trend towards reduced vertical locomotion. These data suggest that a low-frequency brief alarm tone can temporarily disrupt movement, a valuable insight should an alarm be deployed. Further, findings support close collaboration between researchers and institutional facility staff to ensure appropriate acoustic conditions are maintained, whenever possible, for research animals

Image_3_IL-27 alters inflammatory cytokine expression and limits protective immunity against Mycobacterium tuberculosis in a neonatal BCG vaccination model.tif

BackgroundEfforts to control tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (Mtb), have been hampered by the immense variability in protection from BCG vaccination. While BCG protects young children from some forms of TB disease, long-term protection against pulmonary disease is more limited, suggesting a poor memory response. New vaccines or vaccination strategies are required to have a realistic chance of eliminating TB disease. In TB endemic areas, routine immunization occurs during the neonatal period and as such, we hypothesized that inadequate protective immunity elicited by BCG vaccination could be the result of the unique early-life immune landscape. Interleukin (IL)-27 is a heterodimeric cytokine with immune suppressive activity that is elevated in the neonatal period.ObjectiveWe investigated the impact of IL-27 on regulation of immune responses during neonatal BCG vaccination and protection against Mtb.MethodsHere, we used a novel model of neonatal vaccination and adult aerosol challenge that models the human timeline of vaccine delivery and disease transmission.ResultsOverall, we observed improved control of Mtb in mice unresponsive to IL-27 (IL-27Rα-/-) that was consistent with altered expression patterns of IFN-γ and IL-17 in the lungs. The balance of these cytokines with TNF-α expression may be key to effective bacterial clearance.ConclusionsOur findings suggest the importance of evaluating new vaccines and approaches to combat TB in the neonatal population most likely to receive them as part of global vaccination campaigns. They further indicate that temporal strategies to antagonize IL-27 during early life vaccination may improve protection.</p

Image_1_IL-27 alters inflammatory cytokine expression and limits protective immunity against Mycobacterium tuberculosis in a neonatal BCG vaccination model.tif

BackgroundEfforts to control tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (Mtb), have been hampered by the immense variability in protection from BCG vaccination. While BCG protects young children from some forms of TB disease, long-term protection against pulmonary disease is more limited, suggesting a poor memory response. New vaccines or vaccination strategies are required to have a realistic chance of eliminating TB disease. In TB endemic areas, routine immunization occurs during the neonatal period and as such, we hypothesized that inadequate protective immunity elicited by BCG vaccination could be the result of the unique early-life immune landscape. Interleukin (IL)-27 is a heterodimeric cytokine with immune suppressive activity that is elevated in the neonatal period.ObjectiveWe investigated the impact of IL-27 on regulation of immune responses during neonatal BCG vaccination and protection against Mtb.MethodsHere, we used a novel model of neonatal vaccination and adult aerosol challenge that models the human timeline of vaccine delivery and disease transmission.ResultsOverall, we observed improved control of Mtb in mice unresponsive to IL-27 (IL-27Rα-/-) that was consistent with altered expression patterns of IFN-γ and IL-17 in the lungs. The balance of these cytokines with TNF-α expression may be key to effective bacterial clearance.ConclusionsOur findings suggest the importance of evaluating new vaccines and approaches to combat TB in the neonatal population most likely to receive them as part of global vaccination campaigns. They further indicate that temporal strategies to antagonize IL-27 during early life vaccination may improve protection.</p

Image_2_IL-27 alters inflammatory cytokine expression and limits protective immunity against Mycobacterium tuberculosis in a neonatal BCG vaccination model.tif

BackgroundEfforts to control tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (Mtb), have been hampered by the immense variability in protection from BCG vaccination. While BCG protects young children from some forms of TB disease, long-term protection against pulmonary disease is more limited, suggesting a poor memory response. New vaccines or vaccination strategies are required to have a realistic chance of eliminating TB disease. In TB endemic areas, routine immunization occurs during the neonatal period and as such, we hypothesized that inadequate protective immunity elicited by BCG vaccination could be the result of the unique early-life immune landscape. Interleukin (IL)-27 is a heterodimeric cytokine with immune suppressive activity that is elevated in the neonatal period.ObjectiveWe investigated the impact of IL-27 on regulation of immune responses during neonatal BCG vaccination and protection against Mtb.MethodsHere, we used a novel model of neonatal vaccination and adult aerosol challenge that models the human timeline of vaccine delivery and disease transmission.ResultsOverall, we observed improved control of Mtb in mice unresponsive to IL-27 (IL-27Rα-/-) that was consistent with altered expression patterns of IFN-γ and IL-17 in the lungs. The balance of these cytokines with TNF-α expression may be key to effective bacterial clearance.ConclusionsOur findings suggest the importance of evaluating new vaccines and approaches to combat TB in the neonatal population most likely to receive them as part of global vaccination campaigns. They further indicate that temporal strategies to antagonize IL-27 during early life vaccination may improve protection.</p

Deactivation of SARS-CoV-2 with pulsed-xenon ultraviolet light: Implications for environmental COVID-19 control.

ObjectivesProlonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators.MethodsChamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV.ResultsFor hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, &gt;4.54 log10, and &gt;4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in &gt;4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators.ConclusionWith the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2

Les humanités numériques dans une perspective internationale : opportunités, défis, outils et méthodes

Ce numéro de la revue ILCEA se propose d’offrir un aperçu de projets de recherche rendus possibles par une intégration du numérique dans diverses disciplines SHS et aires géographiques, mais aussi de faire état des questionnements des chercheurs qui y ont eu recours, des solutions qu’ils ont mises en place afin de mener à bien leurs travaux et de pistes de réflexion pour l’avenir sur ce terrain encore largement exploratoire. This issue of the ILCEA journal aims to provide an overview of projects made possible by the integration of digital technology in various disciplines of the humanities and geographical areas, but also to report on the questions raised by the researchers who have used it, the solutions they have implemented in order to carry out their work, and the avenues for future reflection in this field, which is still largely exploratory