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

O in Mouth

The poems in O in Mouth are concerned with pleasure and guilt, self and other, form and transgression, orgasms and the weight of the moments after. They focus on orality in poetry and in sex, locating the mouth as the site of all these concerns. Much of this book is written in dialogue with other texts, including Shakespeare’s sonnets, Dante\u27s Vita Nuova, Helene Cixous\u27s The Newly Born Woman, as well as many others, including some of Pablo Neruda’s love poems. While reading representations of eros, I was excited by the passion and desire felt by the lovers; yet I found myself troubled by how, while exalted, the beloved (generally female) was often treated as if she was completely passive, always already dead. Reading, I found myself seeing from the active subject position of the lover, yet I could also see myself in the passive, silent, and often female beloved. The poems in this book attempt to respond to this complicated relationship; they want to participate in the long and rich history of love poetry, but they also speak back (hence the erasures and echoes in L/B ). They desire to slide between the self and other, male and female and locate their Voice in the multiplicity of self that Cixous uses to define bisexuality in The Newly Born Woman. The manuscript begins in sonnets, because sonnets are a memory we keep in our mouths. But these sonnets are echoes, an experiment with the boundaries of this form that reflects their desire to push at the edges of self and voice. Their building tension acts as a framework for the rest of the book, asking the questions which are cyclically repeated throughout. How can we sustain the moments of love, orgasm, pleasure, presence? How do we cope with the fact that eventually we have to drag our bodies from the bed? And where and how do these two modes of living press in on each other? The sections that follow repeat and build upon these themes. Using the mouth as the central place of sexuality and of speaking, the poems think about the push between pleasure and nonpleasure in circles. This book doesn’t treat love as an arching narrative which reaches its climax and ends in denouement. Instead it hopes to mimic the constant having and losing of love that is our experience. It uses the O as a visual and vocal representation of these circles while representing the void that is simultaneously necessary in their existence. The book ends in a confessional mode, following the attempt to sustain pleasure and presence in the cicadas. While one of their formal goals is to look at dull and mundane existence juxtaposed against those moments of lyric pleasure in the cicadas, they find that this delineation is blurry. Pleasure pushes in. Robert Creeley ends his poem, The Language, by saying Speech/ is a mouth. For him, the mouth and what it makes are simultaneous. Earlier in the same poem, Creeley tells us Words/ say everything… I heard words/ and words full// of holes/ aching. Language, by design, must say everything, but this same language leaves us with painful absences. The poems in the following collection are meant to act as mouths and it is in these aching holes I wish to explore love in O in Mouth

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