Cytisine is neuroprotective in female but not male 6-hydroxydopamine lesioned parkinsonian mice and acts in combination with 17-ß-estradiol to inhibit apoptotic endoplasmic reticulum stress in dopaminergic neurons.

Apoptotic endoplasmic reticulum (ER) stress is a major mechanism for dopaminergic (DA) loss in Parkinson's disease (PD). We assessed if low doses of the partial α4ß2 nicotinic acetylcholine receptor agonist, cytisine attenuates apoptotic ER stress and exerts neuroprotection in substantia nigra pars compacta (SNc) DA neurons. Alternate day intraperitoneal injections of 0.2 mg/kg cytisine were administered to female and male mice with 6-hydroxydopamine (6-OHDA) lesions in the dorsolateral striatum, which caused unilateral degeneration of SNc DA neurons. Cytisine attenuated 6-OHDA-induced PD-related behaviors in female, but not in male mice. We also found significant reductions in tyrosine hydroxylase (TH) loss within the lesioned SNc of female, but not male mice. In contrast to female mice, DA neurons within the lesioned SNc of male mice showed a cytisine-induced pathological increase in the nuclear translocation of the pro-apoptotic ER stress protein, C/EBP homologous protein (CHOP). To assess the role of estrogen in cytisine neuroprotection in female mice, we exposed primary mouse DA cultures to either 10 nM 17-ß-estradiol and 200 nM cytisine or 10 nM 17-ß-estradiol alone. 17-ß-estradiol reduced expression of CHOP, whereas cytisine exposure reduced 6-OHDA-mediated nuclear translocation of two other ER stress proteins, activating transcription factor 6 and x-box-binding protein 1, but not CHOP. Taken together, these data show that cytisine and 17-ß-estradiol work in combination to inhibit all three arms (activating transcription factor 6, x-box-binding protein 1, and CHOP) of apoptotic ER stress signaling in DA neurons, which can explain the neuroprotective effect of low-dose cytisine in female mice.

Why do people with chronic obstructive pulmonary disease repeat pulmonary rehabilitation? Perspectives of patients and health professionals.

Many people with chronic obstructive pulmonary disease (COPD) undertake pulmonary rehabilitation more than once. This study examined patient experiences and health professional perspectives regarding repeating pulmonary rehabilitation. Participants were 14 patients with COPD and 15 health professionals. Patients had undertaken pulmonary rehabilitation at a tertiary hospital; health professionals were doctors, physiotherapists, and nurses. Semi-structured interviews were conducted, and data were analyzed using thematic analysis. Patients described improved fitness and better breathing after repeating pulmonary rehabilitation; however, some also reported that repeating required confronting their disease progression. Improved confidence and motivation were an important outcome of repeating. Although most participants had attended community-based exercise classes, they valued the greater intensity of exercise and closer supervision that came with repeating pulmonary rehabilitation. Health professionals reported referring patients to repeat pulmonary rehabilitation if they had worsening functional capacity, an exacerbation, or hospitalization. There was no agreement regarding the optimal time for repeating and many would only re-refer if the patient demonstrated motivation to attend. In conclusion, patients with COPD reported many symptomatic benefits from repeating pulmonary rehabilitation and gained confidence from a supervised program. There was no agreement between health professionals regarding the optimal time to repeat pulmonary rehabilitation.

Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain.

Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population.