Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations

The mechanisms of seizure emergence, and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. Our study shows that the transition to seizure is not a sudden phenomenon,but a slow process characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by the synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We show that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence

Development of sentinel node localization and ROLL in breast cancer in Europe

The concept of a precise region in which to find the lymph nodes that drain the lymph directly from the primary tumor site can be traced back to a century ago to the observations of Jamieson and Dobson who described how cancer cells spread from cancer of the stomach in a single lymph node, which they called the â\u80\u9cprimary glandâ\u80\u9d. However, Cabanas was the first in 1977 to realize the importance of this concept in clinical studies following lymphography performed in patients with penile cancer. Thanks to Mortonâ\u80\u99s studies on melanoma in 1992, we began to understand the potential impact of the sentinel lymph node (SN) on the surgical treatment of this type of cancer. The use of a vital dye (blue dye) administered subdermally in the region surrounding the melanoma lesion led to the identification of the sentinel node, and the vital dye technique was subsequently applied to other types of solid tumors, e.g. breast, vulva. However, difficulties in using this technique in anatomical regions with deep lymphatic vessels, e.g. axilla, led to the development of lymphoscintigraphy, started by Alex and Krag in 1993 on melanoma and breast cancer and optimized by our group at European Institute of Oncology (IEO) in Milan in 1996. Today, lymphoscintigraphy is still considered as the most reliable method for the detection of the SN. In 1996, a new method for the localization of non-palpable breast lesion called radioguided occult lesion localization (ROLL) was also developed at IEO. Retrospective and prospective studies have since shown that the ROLL procedure permits the easy and accurate surgical removal of non-palpable breast lesions, overcoming the limitations of previous techniques such as the wire-guided localization. The purpose of this paper is to describe the evolution of SN biopsy and radioguided surgery in the management of breast cancer. We also include a review of the literature on the clinical scenarios in which SN biopsy in breast cancer is currently used, with particular reference to controversies and future prospects

Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis

The authors would like to thank members of OBD Reference Facility Benjamin Foulkes, Chloe Bird, Emily Corfeld and Matthew Salter for expedient processing of clinical samples on the EpiSwitch™ platform and Magdalena Jeznach and Willem Westra for help with preparation of the manuscript. The study employed samples from the SERA Biobank used with permission and approval of the SERA Approval Group. We gratefully acknowledge the invaluable contribution of the clinicians and operating team in SERA. We would also like to thank Prof. Raju Kucherlapati (Harvard Medical School), and Prof. Jane Mellor (Oxford Univ.), Prof. John O’Shea (National Institute of Health) and Prof. John Isaacs (New Castle Univ.) for their independent and critical review of our study. A list of Scottish Early Rheumatoid Arthritis (SERA) inception cohort investigators is provided in Additional fle 1: Additional Note. Funding This work was funded by Oxford BioDynamics.Peer reviewedPublisher PD

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

WSES guidelines for emergency repair of complicated abdominal wall hernias

Peer reviewe