A Randomized Controlled Trial of High-Intensity Exercise and Executive Functioning in Cognitively Normal Older Adults

BackgroundThere is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function.MethodsNinety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO₂peak.ResultsFirst, the exercise intervention was found to increase cardiorespiratory fitness (VO₂peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants.ConclusionAt the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.     

ADRB2, brain white matter integrity and cognitive ageing in the Lothian Birth Cohort 1936

The non-synonymous mutations arg16gly (rs1042713) and gln27glu (rs1042714) in the adrenergic β-2 receptor gene (ADRB2) have been associated with cognitive function and brain white matter integrity. The current study aimed to replicate these findings and expand them to a broader range of cognitive and brain phenotypes. The sample used is a community-dwelling group of older people, the Lothian Birth Cohort 1936. They had been assessed cognitively at age 11 years, and undertook further cognitive assessments and brain diffusion MRI tractography in older age. The sample size range for cognitive function variables was N = 686–765, and for neuroimaging variables was N = 488–587. Previously-reported findings with these genetic variants did not replicate in this cohort. Novel, nominally significant associations were observed; notably, the integrity of the left arcuate fasciculus mediated the association between rs1042714 and the Digit Symbol Coding test of information processing speed. No significant associations of cognitive and brain phenotypes with ADRB2 variants survived correction for false discovery rate. Previous findings may therefore have been subject to type 1 error. Further study into links between ADRB2, cognitive function and brain white matter integrity is required.     

Retrograde Mitochondrial Transport Is Essential for Organelle Distribution and Health in Zebrafish Neurons

In neurons, mitochondria are transported by molecular motors throughout the cell to form and maintain functional neural connections. These organelles have many critical functions in neurons and are of high interest as their dysfunction is associated with disease. While the mechanics and impact of anterograde mitochondrial movement toward axon terminals are beginning to be understood, the frequency and function of retrograde (cell body directed) mitochondrial transport in neurons are still largely unexplored. While existing evidence indicates that some mitochondria are retrogradely transported for degradation in the cell body, the precise impact of disrupting retrograde transport on the organelles and the axon was unknown. Using long-term, in vivo imaging, we examined mitochondrial motility in zebrafish sensory and motor axons. We show that retrograde transport of mitochondria from axon terminals allows replacement of the axon terminal population within a day. By tracking these organelles, we show that not all mitochondria that leave the axon terminal are degraded; rather, they persist over several days. Disrupting retrograde mitochondrial flux in neurons leads to accumulation of aged organelles in axon terminals and loss of cell body mitochondria. Assays of neural circuit activity demonstrated that disrupting mitochondrial transport and function has no effect on sensory axon terminal activity but does negatively impact motor neuron axons. Taken together, our work supports a previously unappreciated role for retrograde mitochondrial transport in the maintenance of a homeostatic distribution of mitochondria in neurons and illustrates the downstream effects of disrupting this process on sensory and motor circuits.SIGNIFICANCE STATEMENT Disrupted mitochondrial transport has been linked to neurodegenerative disease. Retrograde transport of this organelle has been implicated in turnover of aged organelles through lysosomal degradation in the cell body. Consistent with this, we provide evidence that retrograde mitochondrial transport is important for removing aged organelles from axons; however, we show that these organelles are not solely degraded, rather they persist in neurons for days. Disrupting retrograde mitochondrial transport impacts the homeostatic distribution of mitochondria throughout the neuron and the function of motor, but not sensory, axon synapses. Together, our work shows the conserved reliance on retrograde mitochondrial transport for maintaining a healthy mitochondrial pool in neurons and illustrates the disparate effects of disrupting this process on sensory versus motor circuits.     

Elite female athletes’ experiences and perceptions of the menstrual cycle on training and sport performance

The purpose of the current study was twofold (a) to examine elite female athletes’ experiences of their menstrual cycle, with a focus upon the impact on training and competition performance and (b) the openness of conversation pertaining to the menstrual cycle with coaching and support staff. Following receipt of institutional ethical approval, individual semi‐structured interviews were conducted with 17 elite female athletes (25.5 ± 4.7 years) from multiple sports. Results revealed athletes’ experiencing a natural menstrual cycle reported physical symptoms alongside mood disturbances and reduced motivation to train. The decision to actively control the menstrual cycle was often triggered by a desire to reduce the effect on competition, to lessen anxieties about making required weight or reduce distraction to manage during competition. Athletes indicated an openness to talk about the menstrual cycle to other females, however, there was variation in the comfort athletes experienced regarding talking to male coaches. Overall, the findings highlight the need to educate elite athletes and coaches on the menstrual cycle, considering it in the same light as other physiological functions in sport to improve health, well‐being, and performance. Furthermore, providing education on how to construct positive conversations, equipping individuals with the correct terminology, and confidence to talk about the menstrual cycle will reduce some reservations identified through improved knowledge and understanding.     

The mentorship experience of students and nurses in pre‐registration nursing education: A thematic synthesis of qualitative studies

Mentorship is considered to play a paramount role in empowering nursing students to recieve superlative benefit from clinical placement. Although the new standards for student supervision and assessment approved by the Nursing and Midwifery Council in 2018 seemed to lead to the disillusionment of mentorship, they support clinical education and devotion to nursing students' clinical learning globally. The aim of this synthesis was to review and explore the experiences of mentorship of preregistration nursing students and nurses. A systematic search of databases was performed for qualitative studies published in English from 2000 to 2018. Eleven qualitative studies were selected, from which three analytical themes emerged: mentors' capabilities and readiness for preregistration nursing student mentorship, humanistic approach as foundation to the effectiveness of preregistration nursing student mentorship, and the collaboration of stakeholders in health care and educational settings to enhance preregistration nursing student mentorship. A thematic framework of mentorship in preregistration nursing education was introduced. The thematic synthesis sheds light on how to improve a formal system of mentorship and clinical supervision for nursing education.     

Radiotherapy for SMAD4-negative musculoskeletal lesions from pancreatic cancer

Background

Pancreatic cancer (PC) predominantly metastasizes to liver, lung, and peritoneum. Metastatic disease correlates with SMAD4 status. Musculoskeletal metastases (MSM) are rare in pancreatic cancer. The role of radiation therapy (RT) in patients with musculoskeletal metastases is not clear.

Methods

We present a case of a woman with musculoskeletal metastases of PC evolving 4 years after Whipple’s procedure and adjuvant therapy. She was treated with RT for 7 MSM. Radiation dose was 15–45 Gy, delivered in doses of 2.5–5 Gy per fraction. SMAD4 status was examined by immunohistochemistry. Furthermore we undertook a review of the literature to examine the value of RT in musculoskeletal metastasis of PC.

Results

In the presented patient we treated 7 MSM of SMAD4-mutant PC with RT. RT achieved local control in 4 of the 7 MSM. At the resection margin of one MSM recurrent tumor was observed after RT. The status of one MSM was unknown and one MSM showed local progression. Follow-up revealed progression of pain in 1 of the 7 MSM. Except of hyperpigmentation no side effects occurred. There was no dose–correlation effect on tumor control observed. A review of the literature showed that a musculoskeletotrophic phenotype of metastases is rare in PC. MSM of PC are rapidly increasing soft tissue masses causing pain and loss of anatomical function. RT as a treatment option for musculoskeletal metastasis is described in the current literature in only 2 cases. Radiotherapy aims to achieve local control, pain relief, and to maintain anatomical function.

Conclusion

Radiotherapy is an effective and well-tolerated approach for multiple musculoskeletal metastases of PC.

     

A Comparison of the Efficacy of Various Antioxidants on the Oxidative Stability of Irradiated Polyethylene

Background

Ultrahigh-molecular-weight polyethylene (UHMWPE) is subjected to radiation crosslinking to form highly crosslinked polyethylene (HXLPE), which has improved wear resistance. First-generation HXLPE was subjected to thermal treatment to reduce or quench free radicals that can induce long-term oxidative degeneration. Most recently, antioxidants have been added to HXLPE to induce oxidative resistance rather than by thermal treatment. However, antioxidants can interfere with the efficiency of radiation crosslinking.

Questions/purposes

We sought to identify (1) which antioxidant from among those tested (vitamin E, β-carotene, butylated hydroxytoluene, or pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate]) causes the least reduction of crosslinking; (2) which promotes the greatest oxidative stability; and (3) which had the lowest ratio of oxidation index to crosslink density.

Methods

Medical-grade polyethylene (PE) resin was blended with 0.1 weight % of the following stabilizers: alpha tocopherol (vitamin E), β-carotene, butylated hydroxytoluene (BHT), and pentaerythritol tetrakis [methylene-3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate] (a hindered phenol antioxidant [HPAO]). These blends were compression-molded into sheets and subjected to electron beam irradiation to a dose of 100 kGy. Equilibrium swelling experiments were conducted to calculate crosslink density. Each PE was subjected to accelerated aging for a period of 2 weeks and Fourier transform infrared spectroscopy was used to measure the maximum oxidation. Statistical analysis was conducted using analysis of variance with Fisher’s protected least significant difference in which a p value of < 0.05 was used to define a significant difference.

Results

The least reduction of crosslinking in antioxidant-containing HXLPE was observed with HPAO, which had a crosslink density (n = 6) of 0.167 (effect size [ES] = 0.87; 95% confidence interval [CI], 0.162–0.173) mol/dm³ compared with 0.139 (ES = 1.57; 95% CI, 0.132–0.146) mol/dm³ (p = 0.020) for BHT, 0.131 (ES = 1.77; 95% CI, 0.123–0.139) mol/dm³ (p = 0.004) for β-carotene, and 0.130 (ES = 1.79; 95% CI, 0.124–0.136) mol/dm³ (p = 0.003) for vitamin E, whereas pure HXLPE had a crosslink density of 0.203 (95% CI, 0.170–0.235) mol/dm³ (p = 0.005). BHT-PE had an oxidation index of 0.21 (ES = 13.14; 95% CI, 0.19–0.22) followed by HPAO-PE, vitamin E-PE and β-carotene-PE, which had oxidation indices of 0.28 (ES = 9.68; 95% CI, 0.28–0.29), 0.29 (ES = 9.59; 95% CI, 0.27–0.30), and 0.35 (ES = 6.68; 95% CI, 0.34–0.37), respectively (p < 0.001 for all groups). BHT-PE had the lowest ratio of oxidation index to crosslink density of the materials tested (1.49, ES = 1.94; 95% CI, 1.32–1.66) followed by HPAO-PE (1.70, ES = 1.52; 95% CI, 1.61–1.80), vitamin E-PE (2.21, ES = 0.52; 95% CI, 2.05–2.38), and β-carotene-PE (2.69, ES = -0.43; 95% CI, 2.46–2.93) compared with control PE (2.47, 95% CI, 2.07–2.88) with β-carotene (p = 0.208) and vitamin E (p = 0.129) not being different from the control.

Conclusions

BHT-modified HXLPE was found in this study to have the lowest oxidation index as well as the lowest ratio of oxidation index to crosslink density compared with vitamin E, HPAO, and β-carotene-modified HXLPEs. More comprehensive studies are required such as wear testing using joint simulators as well as biocompatibility studies before BHT-modified HXLPE can be considered for clinical use.

Clinical Relevance

BHT is a synthetic antioxidant commonly used in the polymer industry to prevent long-term oxidative degradation and has been approved by the FDA for use in cosmetics and foodstuffs. It may be an attractive potential stabilizer for HXLPE in total joint replacements.