Synthesis of the European ALARA network 20th workshop 'ALARA for interventional radiology and nuclear medicine'.

The European as low as reasonably achievable(ALARA) network regularly organises workshops on topical issues in radiation protection (RP). The topic of the 20th workshop was: 'ALARA for interventional radiology (IR) and nuclear medicine (NM)'. The objective was to examine the challenges faced when applying the optimisation principle (ALARA) in IR and NM and to consider how ALARA could be better implemented for patient and staff exposures. This memorandum provides a synthesis of the workshop sessions, and recommendations coming from the working groups discussion. Parallels are drawn with the recommendations arising from the 13th EAN workshop on 'ALARA and the medical sector (2011)' to consider how the optimisation challenges in IR and NM have evolved over the past decade. Current levels of exposure are presented along with operational practice and the challenges and opportunities for improvement, both in monitoring and practice. Whilst RP challenges remain, the application of ALARA appears more established in IR compared with experiences reported in 2011. The application of ALARA to emerging technologies in the NM setting is in need of further development to ensure that RP is considered at all stages in the development process of new radiopharmaceuticals. Besides the obvious technical and operational aspects, the importance of education and training, human factors and broadly the RP 'culture' were deemed fundamental to the success of the application of ALARA and where further emphasis is needed. All concerned parties, medical physics experts (MPEs), radiation protection experts, clinical staff, manufacturers and regulators have a role to play in the application of ALARA and this is discussed in the memorandum. Many of the recommendations from the 13th EAN workshop remain applicable today and overlap with the recommendations arising from the 20th workshop. This should prompt attention given that the use of IR and the development of novel radiopharmaceuticals for NM is only anticipated to increase with time.

TNF signaling via TNF receptors does not mediate the effects of short-term exercise on cognition, anxiety and depressive-like behaviors in middle-aged mice.

BACKGROUND: We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR2 receptors mediates the effects of long-term exercise on locomotion, cognition and anxiety, but not depressive-like behavior. We now investigated whether the TNF signaling via its receptors also mediates the effects of short-term exercise on cognition, anxiety and depressive-like behaviors. METHODS: Thirteen-month-old C57BL/6 (WT), TNF-/-, TNFR1-/-, and TNFR2-/- mice were provided with 4 weeks of voluntary wheel running followed by behavioral testing using an established behavioral battery. Each genotype had a respective non-exercise control. RESULTS: There was no interaction between genotype and exercise in any of the tests but the main effect of genotype, and not exercise, were found to be significant in the open field (OF), forced-swim test (FST) and Barnes maze (BM). In the OF, the control and exercise TNFR2-/- mice spent significantly less time in the inner zone than mice in the control and exercise WT and TNF-/- cohorts. In the FST, control and exercise WT mice showed significantly higher immobility time than their control and exercise TNF-/-, TNFR1-/- and TNFR2-/- cohorts. In the BM, the latency to escape over 4 days of training was significantly higher in all KO groups compared to WT, irrespective of exercise. Also, the latency to escape to the original location during the probe trial was higher for control and exercise WT compared to corresponding TNFR1-/- mice. In contrast, the latency to escape to the new location was lower for control and exercise WT compared to control and exercise TNFR1-/- and TNFR2-/- mice. The latency to escape to the new location in exercise groups was longer compared to control within all genotypes. CONCLUSION: While TNF signaling via the TNF receptors mediates cognition, anxiety and depressive-like behaviors independently, it does not mediate the effects of short-term exercise on these behaviors in middle-aged mice.

How timely is access to palliative care medicines in the community? A mixed methods study in a UK city.

OBJECTIVE: To investigate timely access to palliative medicines/drugs (PMs) from community pharmacies to inform palliative care service delivery. DESIGN: Mixed methods in two sequential phases: (1) prospective audit of prescriptions and concurrent survey of patients/representatives collecting PMs from pharmacy and (2) interviews with community pharmacists (CPs) and other healthcare professionals (HCPs). SETTING: Five community pharmacies in Sheffield, UK and HCPs that deliver palliative care in that community. PARTICIPANTS: Phase 1: five CPs: two providing access to PMs within a locally commissioned service (LCS) and three not in the LCS; 55 patients/representatives who completed the survey when accessing PMs and phase 2: 16 HCPs, including five phase 1 CPs, were interviewed. RESULTS: The prescription audit collected information on 75 prescriptions (75 patients) with 271 individual PMs; 55 patients/representatives (73%) completed the survey. Patients/representatives reported 73% of PMs were needed urgently. In 80% of cases, patients/representatives received all PMs on the first pharmacy visit. One in five had to travel to more than one pharmacy to access PMs. The range of PMs stocked by pharmacies was the key facilitating factor. CPs reported practical issues causing difficulty keeping PMs in stock and playing a reactive role with palliative prescriptions. Confidentiality concerns were cited by other HCPs who were reluctant to share key patient information proactively with pharmacy teams. Inadequate information transfer, lack of CP integration into the care of palliative patients and poor HCP knowledge of which pharmacies stock PMs meant patients and their families were not always able to access PMs promptly. CONCLUSIONS: Consistent routine information transfer and integration of pharmacy teams in the care of palliative patients are needed to achieve timely access to PMs. Commissioners of PM access schemes should review and monitor access. HCPs need to be routinely made aware and reminded about the service and its locations.

TNF signalling via the TNF receptors mediates the effects of exercise on cognition-like behaviours.

BACKGROUND: Altered TNF levels are associated with cognitive impairment in depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). Exercise improves cognition-like behaviours, reduces the expression of tumour necrosis factor alpha (TNF), and increases expression of the soluble TNF receptors soluble TNFR1 (sTNFR1) and sTNFR2. We suggest TNF and its receptors are involved in cognitive function and dysfunction, and investigate whether exercise mediates its effects on cognitive function via TNF and its receptors. METHODS: We utilised C57BL/6, TNF-/-, TNFR1-/-, and TNFR2-/- mice to compare exercise to non-exercise control groups to investigate whether exercise exerts its effects on various types of cognition-like behaviours via TNF and its receptors. RESULTS: Recognition memory improved with exercise in WT mice, was impaired in TNFR1-/- exercise mice, showed non-significant impairment with exercise in TNF-/- mice, and no changes in TNFR2-/- mice. In spatial learning there were exercise related improvements in WT mice, non-significant but meaningful impairments evident in TNFR1-/- exercise mice, modest improvement in TNF-/- exercise mice, and potentially meaningful non-significant improvements in TNFR2-/- exercise mice. Moreover, WT and TNFR2-/- mice displayed noteworthy non-significant improvements in spatial memory, whereas TNFR1-/- exercise mice demonstrated non-significant spatial memory impairment. Exercise did not alter cognitive flexibility in any strain. DISCUSSION: TNF receptor signalling via the TNFR1 and TNFR2 appears to mediate the effects of exercise on cognitive-like behaviours. The potential for exercise to regulate human TNF and TNF signalling and cognitive dysfunction needs investigation under inflammatory conditions including depression and neuropsychiatric disorders.

Exercise related anxiety-like behaviours are mediated by TNF receptor signaling, but not depression-like behaviours.

Depression can involve disrupted pro-inflammatory TNF signaling via the TNF receptors TNFR1 and TNFR2, or the soluble TNF receptors sTNFR1 and sTNFR2. However, exercise might attenuate pro-inflammatory signaling in depression and related anxiety. We hypothesized that six months voluntary wheel running exercise would improve depression-like and anxiety-like behaviours in WT and TNFR1-/- mice, but not in TNF-/- and TNFR2-/- mice compared to their respective control mice. METHODS: We investigated the effects of six months voluntary wheel running exercise on open field (OF) and elevated zero maze (EZM) anxiety-like behaviours, and forced swim test (FST) depression-like behaviours in control and exercise WT, TNF-/-, TNFR1-/-, and TNFR2-/- mice with two-way ANOVAs. RESULTS: Exercise reduced of anxiety-like behaviours in TNFR2-/- exercise mice compared to their respective controls. Compared to WT control mice, WT exercise mice displayed significantly reduced EZM anxiety-like behaviours. There were no exercise related changes in FST immobility time. Between-strains analyses found WT control and exercise mice displayed reduced EZM anxiety-like behaviours compared to TNF-/- and TNFR1-/- control and exercise mice, and WT exercise mice displayed reduced anxiety-like behavior compared to TNFR2-/- exercise mice. DISCUSSION: Exercise associated TNFR1 and TNFR2 signaling in concert in WT exercise mice mediated reductions in aspects of anxiety-like behaviours. These findings are consistent with the current view that imbalances in TNF signaling are involved in disrupted affect. Additional studies are needed to further explore the roles of exercise related TNFR1 and TNFR2 signaling in anxiety-like and depression-like behaviours.

Does ceasing exercise induce depressive symptoms? A systematic review of experimental trials including immunological and neurogenic markers.

BACKGROUND: Regular exercise in adults improves depressive symptoms (DS) and major depressive disorder (MDD), however the clinical effects of ceasing exercise are largely unknown. METHODS: Seven databases were searched from inception to December 2017. Eligibility criteria included English language studies investigating the effects of ceasing exercise on DS or MDD in regularly active adults with or without prior DS or MDD. Blood based markers related to exercise cessation (EC) were assessed, if recorded. Studies investigating exercise follow-up periods were excluded. RESULTS: No studies investigated EC in MDD. Six studies including two RCTS and three studies investigating neurogenic and immune biological markers associated with DS met inclusion criteria (152 healthy adults, females n = 50/32.89%). Compared to baseline, EC increased DS after three days, one week, and two weeks. Female participants had significantly more DS than male participants. Following EC, no changes in brain derived neurotrophic factor (BDNF) or tumour necrosis factor alpha (TNF) were evident, however C-reactive protein (CRP) at week one and interleukin 6 (IL6) at week two were reduced. LIMITATIONS: Quality concerns including risks of attrition and reporting bias limit our confidence in these results. CONCLUSIONS: Ceasing regular exercise increases DS in healthy adults, with greater DS in females than males. Contrary to the cytokine/inflammatory hypothesis of depression, DS were associated with reduced CRP and IL6 and without increased TNF. High quality trials are needed to extend this field of research in both healthy and MDD populations.

Arthroscopic technique for treatment of femoroacetabular impingement.

With an increasing understanding of femoroacetabular impingement (FAI) and advancement of the surgical treatment in patients with FAI, various techniques have been published. Successful outcome after arthroscopic hip surgery depends on appropriately reshaping the bony architecture to allow for improved range of motion before impingement symptoms occur, with special attention to preserve the labrum and restore its function. We present our surgical technique for the arthroscopic treatment of FAI.