Diminishing neuronal acidification by channelrhodopsins with low proton conduction.

Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems.

Diminishing neuronal acidification by channelrhodopsins with low proton conduction.

Many channelrhodopsins are permeable to protons. We found that in neurons, activation of a high-current channelrhodopsin, CheRiff, led to significant acidification, with faster acidification in the dendrites than in the soma. Experiments with patterned optogenetic stimulation in monolayers of HEK cells established that the acidification was due to proton transport through the opsin, rather than through other voltage-dependent channels. We identified and characterized two opsins which showed large photocurrents, but small proton permeability, PsCatCh2.0 and ChR2-3M. PsCatCh2.0 showed excellent response kinetics and was also spectrally compatible with simultaneous voltage imaging with QuasAr6a. Stimulation-evoked acidification is a possible source of disruptions to cell health in scientific and prospective therapeutic applications of optogenetics. Channelrhodopsins with low proton permeability are a promising strategy for avoiding these problems. Statement of Significance: Acidification is an undesirable artifact of optogenetic stimulation. Low proton-permeability opsins minimize this artifact while still allowing robust optogenetic control.

Self-efficacy as a prognostic factor and treatment moderator in chronic musculoskeletal pain patients attending pain management programmes: A systematic review.

OBJECTIVE: Evidence on the effectiveness of pain management programmes (PMPs) for chronic pain patients is mixed. Self-efficacy may be associated with outcome of PMPs. The purpose of this systematic review was to assess the role of self-efficacy as a (i) prognostic factor and (ii) moderator of treatment, in chronic musculoskeletal pain (CMP) patients attending a PMP. METHODS: A systematic review of the literature and qualitative synthesis was carried out. Six electronic databases were searched (1989-2020). Studies that measured pain self-efficacy as a prognostic factor or treatment moderator in patients with CMP, who participated in a multidisciplinary PMP were included. Study quality was appraised using the Quality in Prognosis Studies (QUIPS) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Six studies investigating self-efficacy as a prognostic factor were included with a total of 1881 participants. No studies were found assessing self-efficacy as a treatment moderator. Self-efficacy was a prognostic factor for physical functioning in two studies. There was weak evidence for self-efficacy as a prognostic factor for disability, health-related quality of life and pain outcomes and no evidence for psychological variables, disease severity and tender point index following PMPs. Quality of evidence was very low using the GRADE system for each outcome measure. CONCLUSION: Baseline self-efficacy may play a role in physical function outcomes in CMP patients attending a PMP. Higher quality evidence is needed to determine the influence of self-efficacy on outcomes in this setting.

A 5-year evaluation of the emergency contraception enhanced community pharmacy service provided in Wales.

BACKGROUND: Access to emergency contraception (EC) has been a core component of attempts to address high teenage pregnancy rates in Wales. A national service was commissioned in 2011, allowing supply of EC free of charge from community pharmacies (CPs). This study investigated 5 years of the EC service, to describe its use and investigate changes in the pattern of use over time. METHODS: Secondary analyses of data from all National Health Service funded CP EC consultations in Wales between 1 August 2012 and 31 July 2017 (n=181 359). Data comprised standardised clinical and demographic information, in the form of predefined service user responses, submitted for reimbursement by CPs. RESULTS: Overall service provision remained relatively consistent over the study period, with women aged between 13 and 59 years accessing the service. An association was observed between the time since unprotected sexual intercourse and the day on which the service was accessed (Χ2(18)=16 292.327, p<0.001). Almost half (47.9%) of requests were because no contraception had been used, with a strong and positive association for teenagers and women aged 40+ years. A statistically significant and increasing percentage of consultations were accompanied by further sexual health advice (r=0.7, p<0.01). CONCLUSIONS: Access to EC through CPs is contributing to reducing teenage conceptions and termination rates. However, action is needed to increase contraception use in all age groups. Reduced availability of CP services on Sundays is a barrier to timely EC access. Findings support an expanded role for community pharmacists in provision of regular contraception.

Using Evidence-Based Design to Improve Pharmacy Department Efficiency.

Using a case study of a pharmacy department rebuild in the South West of England, this article examines the use of evidence-based design to improve the efficiency and staff well-being with a new design. This article compares three designs, the current design, an anecdotal design, and an evidence-based design, to identify how evidence-based design can improve efficiency and staff well-being by reducing walking time and distance. Data were collected from the existing building and used to measure the efficiency of the department in its current state. These data were then mapped onto an anecdotal design, produced by architects from interviews and workshops with the end users, and an evidence-based design, produced by highlighting functions with high adjacencies. This changed the view on the working processes within the department, shifting away from a focus on the existing robotic dispensing system. Using evidence-based design was found to decrease the walking time and distance for staff by 24%, as opposed to the anecdotal design, which increased these parameters by 9%, and is predicted to save the department 248 min across 2 days in staff time spent walking.