Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are ...bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17β-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.
Recreational and medical use of stimulants among young adults have gained popularity in the United States over the last decade and their use may increase vulnerability to brain biochemical changes ...and addictive behaviors. The long-term effects of chronic stimulant exposure in later adulthood have not been fully elucidated.
Our study investigated whether chronic exposure to methamphetamine (METH), at a dose designed to emulate human therapeutic dosing for ADHD, would promote biochemical alterations and affect sensitivity to the rewarding effects of subsequent METH dosing.
Groups of 3.5-month-old male and female C57BL/6J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 1 month (5 days/week). METH (0.5 mg/kg)-induced conditioned place preference (CPP) was tested in mice to determine the effects of previous METH exposure on reward-related behavior. Mice were randomly assigned to Experiment I (males and females) or Experiment II (females only) in which CPP testing was respectively performed either 0.5 or 5 months after the end of METH injections, at ~5 or 10 months old respectively. The midbrain and striatum, regions involved in reward circuit, were assessed for markers associated with neurotoxicity, dopaminergic function, neuroinflammation and epigenetic changes after behavioral testing.
Previous exposure to chronic METH did not have significant short-term effects on CPP response but led to a decreased CPP response in 10-month-old females. Previous exposure to METH induced some short-term changes to biochemical markers measured in a brain region and sex-dependent manner, while long-term changes were only observed with GFAP and KDM5C.
In conclusion, our data suggest sex- and post-exposure duration-dependent outcomes and warrant further exploration of the long-term neurobehavioral consequences of psychostimulant use in both sexes.
Rationale
Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these ...psychostimulants and how they interact with age have not been fully studied.
Objectives
Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments.
Methods
Groups of 4-month-old male and female C57BL/6 J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7, and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing.
Results
Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females, and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition; however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males.
Conclusion
In
conclusion
, cognitive and motor functions were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.
Treatment of Alzheimer’s disease (AD) has been limited to managing of symptoms or anti-amyloid therapy with limited results and uncertainty. Seeking out new therapies that can reverse the effects of ...this devastating disease is important. Hyperbaric oxygen (HBO) therapy could be such a candidate as it has been shown to improve brain function in certain neurological conditions. Furthermore, the role sex plays in the vulnerability/resilience to AD remains equivocal. An understanding of what makes one sex more vulnerable to AD could unveil new pathways for therapy development. In this study, we investigated the effects of HBO on cognitive, motor, and affective function in a mouse model of AD (5xFAD) and assessed protein oxidation in peripheral tissues as a safety indicator. The motor and cognitive abilities of 5xFAD mice were significantly impaired. HBO therapy improved cognitive flexibility and associative learning of 5xFAD females but not males, but HBO had no effect other aspects of cognition. HBO also reversed AD-related declines in balance but had no impact on gait and anxiety-like behavior. HBO did not affect body weights or oxidative stress in peripheral tissues. Our study provides further support for HBO therapy as a potential treatment for AD and emphasizes the importance of considering sex as a biological variable in therapeutic development. Further investigations into the underlying mechanisms of HBO’s sex-specific responses are warranted, as well as optimizing treatment protocols for maximum benefits.
Minor changes (~0.1 m/s) in human gait speed are predictive of various measures of decline and can be used to identify at-risk individuals prior to further decline. These associations are possible ...due to an abundance of human clinical research. However, age-related gait changes are not well defined in rodents, even though rodents are used as the primary pre-clinical model for many disease states as well as aging research. Our study investigated the usefulness of a novel automated system, the CatWalk™ XT, to measure age-related differences in gait. Furthermore, age-related functional declines have been associated with decreases in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular shift. Therefore the secondary aim of this study was to determine whether chronic glutathione deficiency led to exacerbated age-associated impairments. Groups of male and female wild-type (gclm
) and knock-out (gclm
) mice aged 4, 10 and 17 months were tested on the CatWalk and gait measurements recorded. Similar age-related declines in all measures of gait were observed in both males and females, and chronic glutathione depletion was associated with some delays in age-related declines, which were further exacerbated. In conclusion, the CatWalk is a useful tool to assess gait changes with age, and further studies will be required to identify the potential compensating mechanisms underlying the effects observed with the chronic glutathione depletion.
Background: The efficient use of operating theatres is important to ensure optimum cost–benefit for the hospital and to clear waiting lists. This audit uses the orthopaedic trauma theatre as a model ...to assess the theatre efficiency at our institution.
Methods: We performed a retrospective audit using data gathered from the operating theatre database at our institution. We considered each component of the operating theatre process and integrated them to give a combined value for surgical and anaesthetic time (end utilization) and total theatre efficiency (operating theatre utilization).
Results: Results showed that relative to the standards set, changeover time and start times were sub‐standard, with consistently prolonged changeovers and late starts. End utilization and operating theatre utilization were 78.8 and 81%, against a standard of 77 and 85–90%, respectively. However, these figures may be misleading due to sub‐standard performance in changeover time and other variables.
Conclusions: We have highlighted inefficiency in the orthopaedic trauma theatre at our institution and suggest various strategies to improve this that may be applied universally.
To examine the treatment recommendation patterns among urologists and radiation oncologists, the level of concordance or discordance between physician recommendations, and the association between ...physician recommendations and the treatment that patients received.
The study was a secondary analysis of data from a randomized clinical trial conducted November 2010 to April 2014 (NCT02053389). Eligible participants were patients from the trial who saw both specialists. The primary outcome was physician recommendations that were scored using an adapted version of the validated PhyReCS coding system. Secondary outcomes included concordance between physician recommendations and the treatment patients received.
Participants were 108 patients (Mean age 61.9 years; range 43-82; 87% non-Hispanic White). Urologists were more likely to recommend surgery (79% of recommendations) and radiation oncologists were more likely to recommend radiation (68% of recommendations). Recommendations from the urologists and radiation oncologists were concordant for only 33 patients (30.6%). Most patients received a treatment that both physicians recommended (59%); however, 35% received a treatment that only one of their physicians recommended. When discordant, urologists more often recommended surgery and radiation oncologists recommended radiation and surgery as equally appropriate options.
Urologists and radiation oncologists are more likely to differ than agree in their treatment recommendations for the same patients with clinically localized prostate cancer and more likely to favor treatment aligned with their specialty. Additional studies are needed to better understand how patients make decisions after meeting with two different specialists to inform the development of best practices within oncology clinics.
Abstract
We present the results of a stellar population analysis of 72 Ly
α
-emitting galaxies (LAEs) in GOODS-N at 1.9 <
z
< 3.5 spectroscopically identified by the Hobby−Eberly Telescope Dark ...Energy Experiment (HETDEX). We provide a method for connecting emission-line detections from the blind spectroscopic survey to imaging counterparts, a crucial tool needed as HETDEX builds a massive database of ∼1 million Ly
α
detections. Using photometric data spanning as many as 11 filters covering 0.4 <
λ
(
μ
m) < 4.5 from the Hubble Space Telescope and Spitzer Space Telescope, we study the objects’ global properties and explore which properties impact the strength of Ly
α
emission. We measure a median stellar mass of
0.8
−
0.5
+
2.9
×
10
9
M
⊙
and conclude that the physical properties of HETDEX spectroscopically selected LAEs are comparable to LAEs selected by previous deep narrowband studies. We find that stellar mass and star formation rate correlate strongly with the Ly
α
equivalent width. We then use a known sample of
z
> 7 LAEs to perform a protostudy of predicting Ly
α
emission from galaxies in the epoch of reionization, finding agreement at the 1
σ
level between prediction and observation for the majority of strong emitters.
Abstract
Background
The EDITH service provides an alternative to Emergency Department (ED) attendance for the older adult by providing emergency care in the person home. It is imperative to explore ...how this service is received by the key stakeholders in order to ensure it is meeting the needs of older adults and to improve and diversify same.
Methods
A patient feedback survey was circulated to patients and family members who received the EDITH service. A postal option and a QR code leading to an online option were utilised. 50 surveys were randomly selected for inclusion. Quantitative data was analysed via paper count method and thematic analysis was completed for the qualitative data.
Results
74% rated the service as “excellent”, 22% “very good” and 4% “good”. Alternative options to the service were identified as “going to ED” 22% , “going to GP” 22%, “waited until they would get better” 4%, “waited until they got worse” 2%, “would do nothing” 6%. 80% rated the combined expertise of a doctor and OT as “extremely important”, 94% rated the home visit aspect as “extremely important” and 90% rated ED avoidance as “extremely important”. Key themes that emerged regarding what the service does well included “personalised care”, “ED avoidance”, “compassion” and “timeliness of service”. Areas for improvement included “improving communication loop to both patients and/or community services! and “ability to directly access the service”. 95% of respondents advised they would or have already recommended the service to others. Of note, a key theme in the comments section was the need for a similar service in other hospitals.
Conclusion
The EDITH service appears to be meeting stake-holders expectations, areas for improvement have been identified and are currently being addressed. It is imperative to obtain the perception of the service user and to tailor interventions accordingly, this feedback is invaluable in order to meet future service needs.
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