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Graphical AbstractHighlights d Aged mice form contextual memory like young mice, but reconsolidation is impaired d Only in young mice is contextual memory formation associated with structural LTP d In aged mice, contextual memory formation correlates with multi-innervated spines d Inhibition of multi-innervated spines impairs memory in aged but not young mice SUMMARY Long-lasting changes at synapses enable memory storage in the brain. Although aging is associated with impaired memory formation, it is not known whether the synaptic underpinnings of memory storage differ with age. Using a training schedule that results in the same behavioral memory formation in young and aged mice, we examined synapse ultrastructure and molecular signaling in the hippocampus after contextual fear conditioning. Only in young, but not old mice, contextual fear memory formation was associated with synaptic changes that characterize well-known, long-term potentiation, a strengthening of existing synapses with one input. Instead, old-age memory was correlated with generation of multi-innervated dendritic spines (MISs), which are predominantly two-input synapses formed by the attraction of an additional excitatory, presynaptic terminal onto an existing synapse. Accordingly, a blocker used to inhibit MIS generation impaired contextual fear memory only in old mice. Our results reveal how the synaptic basis of hippocampal memory storage changes with age and suggest that these distinct memory-storing mechanisms may explain impaired updating in old age. Sigma Plot Systat software https://systatsoftware.com/sp/download.html Photomerge TM CS6 Adobe Photoshop CS6 https://www.adobe.com/uk SEM. Align 1.26b program 1.26b program

BackgroundManagement of the axilla in breast cancer is becoming increasingly conservative. Patients identified with a low axillary nodal burden (two or fewer involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node clearance (cANC). ‘Fast track’ to ANC in patients with involved nodes on pre-operative ultrasound may be over-treating a subgroup of these patients with low nodal burden, which would have precluded their need for ANC. This systematic review assesses the proportion of patients with involved nodes on pre-operative axillary ultrasound, which would fit low axillary burden criteria.MethodsMeta-analysis of studies comparing axillary burden of breast cancer patients identified as pre-operative ultrasound negative versus positive was performed. The primary outcome measure was the number of patients with two or fewer involved nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals (CIs), means and probabilities of identifying two or fewer involved nodes versus greater than two were calculated.ResultsSix studies reported the axillary burden in 4271 patients who were either directed straight to ANC or cANC after SNB. There was a significantly greater axillary burden in the ultrasound positive versus negative groups (OR 5.95, 95% CI 5.80–6.11) with mean nodal retrieval values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively. Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of ultrasound positive patients possessed low axillary burden.ConclusionsPre-operative ultrasound positive patients have significantly higher axillary burden. However, nearly half do fit the criteria of low axillary burden and could be considered for omission of ANC.

Fracture clinic services are under significant pressures to meet patients' expectations of a high-quality service. The virtual fracture clinic has shown early promise in helping to reduce such pressures. We used the virtual fracture clinic for hand and wrist injuries treated in the orthopaedic fracture clinic and used key quality indicators to measure improvement. Over the first 21 months, key patient outcome measures and satisfaction scores for patients discharged from the virtual fracture clinic with education to self-care were excellent. Our results show that a virtual fracture clinic model can be applied to provide high-quality care for hand and wrist injuries. The main advantage of the virtual fracture clinic is its ability to direct patients to the right person for timely treatment. We conclude from our 21-month experience that this model of care allows safe, effective, patient-centred, efficient and equitable care to the patients with hand and wrist fractures. Level of evidence: IV

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Purpose The steady move towards axillary conservatism in breast cancer is based on studies demonstrating that axillary node clearance affords no survival benefit in a subset of patients with a positive pre-operative axillary ultrasound (AUS). However, less attention has been paid to AUS-negative patients who receive sentinel node biopsy as standard. Methods Previously assembled systematic review data was reassessed to evaluate nodal burden amongst patients with breast cancer and a clinically and radiologically negative axilla. Results Pooled data from four cohort studies reporting pre-operative axillary ultrasound in 5139 patients with breast cancer show it has a negative predictive rate of 0.951 (95% confidence interval 0.941-0.960). Conclusions Reconsidering the use of ultrasound in patients with early breast cancer and non-palpable axillae reveals that sentinel node biopsy itself may represent surgical over-treatment in patients with a negative axillary ultrasound. The implications of this on the future of surgical management of the axilla are discussed.

ObjectivesBrain tumours lead to significant morbidity including a neurocognitive, physical and psychological burden of disease. The extent to which they impact the multiple domains of health is difficult to capture leading to a significant degree of unmet needs. Mobile health tools such as Vinehealth have the potential to identify and address these needs through real-world data generation and delivery of personalised educational material and therapies. We aimed to establish the feasibility of Vinehealth integration into brain tumour care, its ability to collect real-world and (electronic) patient-recorded outcome (ePRO) data, and subjective improvement in care.DesignA mixed-methodology IDEAL stage 1 study.SettingA single tertiary care centre.ParticipantsSix patients consented and four downloaded and engaged with the mHealth application throughout the 12 weeks of the study.Main outcome measuresOver a 12-week period, we collected real-world and ePRO data via Vinehealth. We assessed qualitative feedback from mixed-methodology surveys and semistructured interviews at recruitment and after 2 weeks.Results565 data points were captured including, but not limited to: symptoms, activity, well-being and medication. EORTC QLQ-BN20 and EQ-5D-5L completion rates (54% and 46%) were impacted by technical issues; 100% completion rates were seen when ePROs were received. More brain cancer tumour-specific content was requested. All participants recommended the application and felt it improved care.ConclusionsOur findings indicate value in an application to holistically support patients living with brain cancer tumours and established the feasibility and safety of further studies to more rigorously assess this.

Introduction:The use of neo-adjuvant radiotherapy (NRT) has been proven effective at improving cancer related outcome measures, including overall-survival (OS) in the management of solid cancers. However, its utilisation in breast cancer has not been explored to the extent of neo-adjuvant chemotherapy (NAC). The evidence for the application of NRT in breast cancer is evaluated.Methods: PubMed, Embase and the Cochrane Library databases were searched systematically in August 2020 for studies that addressed the role of NRT in the treatment of breast cancer. Studies were deemed eligible if they reported on objective outcome measurements of OS, disease free-survival (DFS) or pathological complete response (pCR) and attained a satisfactory quality assessment.Findings: A total of 23 studies reported upon 3,766 patients who had received NRT of which 3,233 also received NAC concurrently (neo-adjuvant chemo-radiotherapy (NCRT)). The pCR values ranged from 14% to 42%, 5-year DFS 61.4% to 81% and 5-year OS 71.6% to 84.2%. Complications were confined to radiation dermatitis with no cases of implant loss reported during breast reconstruction. The application of NRCT alone showed no significant difference in OS or DFS compared to NCRT followed by surgery.Interpretation: Numbers of patients receiving exclusively NRT is small. However, NCRT is oncologically safe with a low side-effect profile including preceding breast reconstruction. Potential benefits include precise cancer volume targeting, chemosensitisation, elimination of delays in adjuvant therapies and alternatives to chemotherapy in oestrogen receptor positive patients. These factors warrant further exploration within randomised controlled-trials.