The Interplay of Solvation and Polarization Effects on Ion Pairing in Nanoconfined Electrolytes.

The nature of ion-ion interactions in electrolytes confined to nanoscale pores has important implications for energy storage and separation technologies. However, the physical effects dictating the structure of nanoconfined electrolytes remain debated. Here we employ machine-learning-based molecular dynamics simulations to investigate ion-ion interactions with density functional theory level accuracy in a prototypical confined electrolyte, aqueous NaCl within graphene slit pores. We find that the free energy of ion pairing in highly confined electrolytes deviates substantially from that in bulk solutions, observing a decrease in contact ion pairing but an increase in solvent-separated ion pairing. These changes arise from an interplay of ion solvation effects and graphene's electronic structure. Notably, the behavior observed from our first-principles-level simulations is not reproduced even qualitatively with the classical force fields conventionally used to model these systems. The insight provided in this work opens new avenues for predicting and controlling the structure of nanoconfined electrolytes.

Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia.

Nuclear factor I-C (NFIC) belongs to a family of NFI transcription factors that binds to DNA through CAATT-boxes and are involved in cellular differentiation and stem cell maintenance. Here we show NFIC protein is significantly overexpressed in 69% of acute myeloid leukemia patients. Examination of the functional consequences of NFIC overexpression in HSPCs showed that this protein promoted monocytic differentiation. Single-cell RNA sequencing analysis further demonstrated that NFIC overexpressing monocytes had increased expression of growth and survival genes. In contrast, depletion of NFIC through shRNA decreased cell growth, increased cell cycle arrest and apoptosis in AML cell lines and AML patient blasts. Further, in AML cell lines (THP-1), bulk RNA sequencing of NFIC knockdown led to downregulation of genes involved in cell survival and oncogenic signaling pathways including mixed lineage leukemia-1 (MLL-1). Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML.

The PROCESS 2020 Guideline: Updating Consensus Preferred Reporting Of CasESeries in Surgery (PROCESS) Guidelines.

INTRODUCTION: The PROCESS Guidelines were first published in 2016 and were last updated in 2018. They provide a structure for reporting surgical case series in order to increase reporting robustness and transparency, and are used and endorsed by authors, journal editors and reviewers alike. In order to drive forwards reporting quality, they must be kept up to date. As such, we have updated these guidelines via a DELPHI consensus exercise. METHODS: The updated guidelines were produced via a DELPHI consensus exercise. Members from the previous DELPHI group were again invited, alongside editorial board members and peer reviewers of the International Journal of Surgery and the International Journal of Surgery Case Reports. An online survey was completed by this expert group to indicate their agreement with proposed changes to the checklist items. RESULTS: A total of 53 surgical experts agreed to participate and 49 (92%) completed the survey. The responses and suggested modifications were incorporated into the previous 2018 guidelines. There was a high degree of agreement amongst the PROCESS Group, with all but one of the PROCESS items receiving over 70% of scores ranging 7-9. CONCLUSION: A DELPHI consensus exercise was completed and an updated and improved PROCESS Checklist is now presented.

A protocol for wide awake local anaesthetic no tourniquet (WALANT) hand surgery in the context of the coronavirus disease 2019 (COVID-19) pandemic.

There are new and unique challenges to emergency surgery service provision posed by the Coronavirus disease 2019 global pandemic. It is in the best interests of patients for care providers to streamline services where possible to maximise the number of cases that can be performed by limited surgical and anaesthetic teams, as well as minimising patient interactions and admission times to reduce potential spread of the virus. There is evidence that wide awake local anaesthetic no tourniquet (WALANT) hand and upper limb surgery can meet this need in a number of ways, including reduced pre-operative work up, the lack of a need for an anaesthetist or ventilator, shorter inpatient stays and improved cost efficiencies. Though updated national guidelines exist that advocate increased use of WALANT surgery in response to the pandemic there are not yet clear protocols to facilitate this. We outline a protocol being developed at one UK Major Trauma Centre tailored to the expansion of WALANT hand and upper limb emergency surgery with particular emphasis on facilitating timely surgical care while minimising healthcare encounters pre and post-operatively. This will serve to reduce potential transmission of the virus and create cost efficiencies to free funding for COVID-19 related care. Our protocol is easily replicable and may be of benefit to other centres dealing with emergency upper limb surgery in the new climate of COVID-19.

Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 2 (surgical prioritisation).

The Coronavirus (COVID-19) Pandemic represents a once in a century challenge to human healthcare with over 4.5 million cases and over 300,000 deaths thus far. Surgical practice has been significantly impacted with all specialties writing guidelines for how to manage during this crisis. All specialties have had to triage the urgency of their daily surgical procedures and consider non-surgical management options where possible. The Pandemic has had ramifications for ways of working, surgical techniques, open vs minimally invasive, theatre workflow, patient and staff safety, training and education. With guidelines specific to each specialty being implemented and followed, surgeons should be able to continue to provide safe and effective care to their patients during the COVID-19 pandemic. In this comprehensive and up to date review we assess changes to working practices through the lens of each surgical specialty.

Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 1.

The Coronavirus (COVID-19) pandemic has resulted in over 4.5 million confirmed cases and over 300,000 deaths. The impact of COVID-19 on surgical practice is widespread, ranging from workforce and staffing issues, procedural prioritisation, viral transmission risk intraoperatively, changes to perioperative practice and ways of working alongside the impact on surgical education and training. Whilst there has been a growing literature base describing the early clinical course of COVID-19 and on aspects of critical care related to treating these patients, there has been a dearth of evidence on how this pandemic will affect surgical practice. This paper seeks to review the current evidence and offers recommendations for changes to surgical practice to minimise the effect of the COVID-19 pandemic.

Evidence based management guideline for the COVID-19 pandemic - Review article.

COVID-19 has now been declared a pandemic. To date, COVID-19 has affected over 2.5 million people worldwide, resulting in over 170,000 reported deaths. Numerous preventative strategies and non-pharmaceutical interventions have been employed to mitigate the spread of disease including careful infection control, the isolation of patients, and social distancing. Management is predominantly focused on the provision of supportive care, with oxygen therapy representing the major treatment intervention. Medical therapy involving corticosteroids and antivirals have also been encouraged as part of critical management schemes. However, there is at present no specific antiviral recommended for the treatment of COVID-19, and no vaccine is currently available. Despite the strategic implementation of these measures, the number of new reported cases continues to rise at a profoundly alarming rate. As new findings emerge, there is an urgent need for up-to-date management guidelines. In response to this call, we review what is currently known regarding the management of COVID-19, and offer an evidence-based review of current practice.

Use of Wide-Awake Local Anaesthetic No Tourniquet (WALANT) in upper limb and hand surgery: A systematic review protocol.

INTRODUCTION: Wide Awake Local Anaesthetic No Tourniquet (WALANT) technique has been developed to eliminate tourniquet pain during upper limb and hand surgery whilst also improving utilisation of operating theatre time and inpatient stay, however inconclusive data still limits the techniques uptake. Here presents a protocol for a systematic review to collate findings to produce conclusive data on efficacy of WALANT. METHODS: This systematic review will be registered a priori. All study designs defined by the Oxford Centre for Evidence-Based Medicine will be included in the search. "WALANT" in "upper limb" and "hand" surgery will be investigated as per the devised search strategy. 18 electronic databases will be searched, including PubMed, Medline and Embase in addition to a Grey literature search. Two independent teams of 3 researchers will screen all relevant titles, abstracts and subsequent full texts for suitability. Data will be extrapolated and entered into a preformatted database for analysis. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal and presented at both national and international conferences within the field of plastic and orthopaedic surgery. This review aims to inform surgical practice and policy.

World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19).

An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.