Glutathione accelerates sodium channel inactivation in excised rat axonal membrane patches

The effects of glutathione were studied on the gating behaviour of sodium channels in membrane patches of rat axons. Depolarizing pulses from –120 to –40 mV elicited sodium currents of up to 500 pA, indicating the simultaneous activation of up to 250 sodium channels. Inactivation of these channels in the excised, inside-out configuration was fitted by two time constants ( h1=0.81 ms; h2= 5.03 ms) and open time histograms at 0 mV revealed a biexponential distribution of channel openings ( short=0.28 ms; long=3.68 ms). Both, the slow time constant of inactivation and the long lasting single channel openings disappeared after addition of the reducing agent glutathione (2–5 mM) to the bathing solution. Sodium channels of excised patches with glutathione present on the cytoplasmatic face of the membrane had inactivation kinetics similar to channels recorded in the cell-attached configuration. These observations indicate that redox processes may contribute to the gating of axonal sodium channels

Sentinel lymph node biopsy with one-step nucleic acid assay relegates the need for preoperative ultrasound-guided biopsy staging of the axilla in patients with early stage breast cancer

Avoiding axillary node clearance in patients with early stage breast cancer and low‑burden node‑positive axillary disease is an emerging practice. Informing the decision to adopt axillary conservation is examined by comparing routine preoperative axillary staging using ultrasound (AUS) ± AUS biopsy (AUSB) with intraoperative staging using sentinel lymph node biopsy (SLNB) and a one‑step nucleic acid cytokeratin‑19 amplification assay (OSNA). A single‑centre, retrospective cohort study of 1,315 consecutive new diagnoses of breast cancer in 1,306 patients was undertaken in the present study. An AUS ± AUSB was performed on all patients as part of their initial assessment. Patients who had a normal ultrasound (AUS‑) or negative biopsy (AUSB‑) followed by SLNB with OSNA ± axillary lymph node dissection (ALND), and those with a positive AUSB (AUSB+), were assessed. Tests for association were determined using a χ2 and Fisher's Exact test. A total of 266 (20.4%) patients with cT1‑3 cN0 staging received 271 AUSBs. Of these, 205 biopsies were positive and 66 were negative. The 684 patients with an AUS‑/AUSB‑assessment proceeded to SLNB with OSNA. AUS sensitivity and negative predictive value (NPV) were 0.53 [0.44‑0.62; 95% confidence interval (CI)] and 0.58 (0.53‑0.64, 95% CI), respectively. Using a total tumour load cut‑off of 15,000 copies/µl to predict ≥2 macro‑metastases, the sensitivity and NPV for OSNA were 0.82 (0.71‑0.92, 95% CI) and 0.98 (0.97‑0.99, 95% CI) (OSNA vs. AUS P<0.0001). Of the AUSB+ patients, 51% had ≤2 positive nodes following ALND and were potentially over‑treated. Where available, SLNB with OSNA should replace AUSB for axillary assessment in cT1‑2 cN0 patients with ≤2 indeterminate nodes seen on AUS

Intraoperative prediction of the two axillary lymph node macrometastases threshold in patients with breast cancer using a one‑step nucleic acid cytokeratin‑19 amplification assay

The aim of the present study was to assess the sensitivity, specificity and practicality of using a one‑step nucleic acid amplification (OSNA) assay during breast cancer staging surgery to predict and discriminate between at least 2 involved nodes and more than 2 involved nodes and facilitate the decision to provide axillary conservation in the presence of a low total axillary node tumour burden. A total of 700 consecutive patients, not treated with neo‑adjuvant chemotherapy, received intraoperative sentinel lymph node (SLN) analysis using OSNA for cT1‑T3 cN0 invasive breast cancer. Patients with at least one macrometastasis on whole‑node SLN analysis underwent axillary lymph node dissection (ALND). The total tumour load (TTL) of the macrometastatic SLN sample was compared with the non‑sentinel lymph node (NSLN) status of the ALND specimen using routine histological assessment. In total, 122/683 patients (17.9%) were found to have an OSNA TTL indicative of macrometastasis. In addition, 45/122 (37%) patients had NSLN metastases on ALND with a total positive lymph node burden exceeding the American College of Surgeons Oncology Group Z0011 trial threshold of two macrometastatic nodes. The TTL negative predictive value was 0.975 [95% confidence interval (CI), 0.962‑0.988]. The area under the curve for the receiver operating characteristic curve was 0.86 (95% CI, 0.81‑0.91), indicating that SLN TTL was associated with the prediction (and partitioning) of total axillary disease burden. OSNA identifies a TTL threshold value where, in the presence of involved SLNs, ALND may be avoided. This technique offers objective confidence in adopting conservative management of the axilla in patients with SLN macrometastases

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Triathlon &amp; Endurance Sports

Relative Energy Deficiency in Sport (RED-S) is a clinical syndrome comprising low energy availability (LEA) as a result of over-training and a negative calorific balance. This syndrome has a wide range of biological, physiological and psychological effects on athletes. These include hormonal changes, low bone density and depression. Diagnosis of RED-S is challenging, as often initial signs are subtle and not widely recognized by general physicians, and access to imaging can be difficult.In this narrative review we discuss the consequences of RED-S, risk factors for the condition and management. Emergence of educational resources such as the BASEM (British Association of Sports and Exercise Medicine) Health and Performance website and the RED-S Clinical Assessment Tool (CAT) is improving understanding of this condition.We highlight a literature gap which is leading to difficulty identifying and managing athletes with health consequences subsequent to low energy availability. Notably, there is a dearth of research in para-athletes, minority group athletes and adolescents.Thus, we propose an increase in implementation of previous research and further funding for large scale studies to define the long-term health and performance consequences of LEA, which will in turn educate and lead to better outcomes for patients.&amp;nbsp; Key Words: Female Athlete, Low Energy Availability, Clinical Syndrome, Athlete

Combined use of the chemitrode with osmotic minipumps for experimental brain research

This paper describes a simple-to-build minipump-chemitrode assembly which can be used for long term electrophysiological, chemical and behavioural studies. This system consists of an osmotic minipump, a cannula and an array of nine electrodes which are connected to a miniature Winchester Socket. A detailed plan for construction of both the chemitrode and the minipump-chemitrode is given together with some suggestions for possible usages in brain research(such as kindling). The osmotic minipump consists of a collapsible reservoir of flexible, impermeable material, surrounded by a sealed layer containing an osmotic agent--all of which is contained by a semipermeable membrane. Imbibed water generates hydrostatic pressure on the flexible lining of the reservoir, gradually compressing it, producing a constant flow of its contents through the delivery portal