Due to the increasing prominence of antibiotic resistance, novel drug discovery and delivery approaches targeting bacteria are essential. In this work we evaluate a prodrug design to improve the cytotoxic profile of polycationic oligothioetheramides (oligoTEAs), which are promising antimicrobials. Herein we chemically modify the oligoTEA, PDT-4G, with a polyethylene glycol (PEG) and show that 1, 2, and 5 kDa PEGs mitigate cytotoxicity. As PEGylation reduces antibacterial activity, we evaluate two peptide linkers which, unlike oligoTEAs, are susceptible to proteolytic cleavage in serum. To gain insight into the prodrug reactivation, two linkers were tested, the 5-residue peptide sequence LMPTG, and the dipeptide sequence VC-PABC. In the presence of 20 % serum, prodrugs made with the VC-PABC linker successfully inhibited bacterial growth. Overall, we observed reactivation of oligoTEAs facilitated by serum protease cleavage of the peptide linkers. This work opens the door to the future design of antimicrobial prodrugs with tunable release profiles.
  This study examined the short-term and long-term mortality of community- and hospital-acquired hypernatraemia in a large cohort of general hospitalised patients, and the impact of delayed serum sodium correction in hypernatraemic patients.
 
  Adult patients admitted to Mayo Clinic Rochester from 2011 to 2013 were examined. The patients with admission serum sodium ≥138mEq/L and at least 2 serum sodium measurements during hospitalisation were included. Hypernatraemia was defined as serum sodium ≥143mEq/L. The patients were categorised into three groups based on serum sodium at admission and during hospitalisation (a) normal serum sodium, (b) community-acquired hypernatraemia and (c) hospital-acquired hypernatraemia. Outcomes included hospital mortality and 1-year mortality after hospital discharge amongst hospital survivors.
 
  Of 25781 eligible patients, 45% had normal serum sodium, 20% had community-acquired hypernatraemia and 35% had hospital-acquired hypernatraemia. In adjusted analysis, odds ratios (ORs) o 3 is associated with increased mortality.
 Hypernatraemia, regardless of acquisition origin, is associated with elevated short-term and long-term mortality. Hospital-acquired hypernatraemia was more common and had a higher short-term mortality than community-acquired hypernatraemia. Failure to correct hypernatraemia by hospital day 3 is associated with increased mortality.Excising the nitrogen in secondary amines, and coupling the two residual fragments is a skeletal editing strategy that can be used to construct molecules with new skeletons, but which has been largely unexplored. Here we report a versatile method of N-atom excision from N-heterocycles. The process uses readily available N-heterocycles as substrates, and proceeds by N-sulfonylazidonation followed by the rearrangement of sulfamoyl azide intermediates, providing various cyclic products. Examples are provided of deletion of nitrogen from natural products, synthesis of chiral O-heterocycles from commercially available chiral β-amino alcohols, formal inert C-H functionalization through a sequence of N-directed C-H functionalization and N-atom deletion reactions in which the N-atom can serve as a traceless directing group.
  BRAF inhibitors such as encorafenib and vemurafenib in combination with MEK inhibitors are commonly used for the treatment of patients with BRAF V600-mutant melanoma.
 
  A patient with relapsed metastatic melanoma with a BRAF V600 mutation was started on treatment with vemurafenib and cobimetinib.  https://www.selleckchem.com/products/atn-161.html  Within 2 weeks of treatment start, he was hospitalized and diagnosed with encephalitis through a lumbar puncture and treated with corticosteroids, with subsequent normalization of cerebrospinal fluid (CSF) findings. When he recovered and was switched to encorafenib treatment, the same symptoms recurred, and the patient was treated with high-dose steroids and intravenous immunoglobulin, again with improvement in his CSF. He has not had a relapse of his symptoms since BRAF inhibitor treatment was permanently discontinued.
 
  This is the first known report of a patient who has developed encephalitis because of treatment with BRAF inhibitors.
 This is the first known report of a patient who has developed encephalitis because of treatment with BRAF inhibitors.
  In New South Wales (NSW), Australia, trauma accounts for 6% of deaths. Trauma patients receiving definitive care in regional trauma centres are 34% more likely to have a fatal outcome compared to level 1 centres. Following the implementation of the NSW State Trauma Plan where patients with major trauma are fast tracked to regional trauma services, should NSW rural surgeons and retrieval doctors continue to receive surgical training in neurotrauma?
 
  The study's primary objective was to ascertain which NSW regional and rural hospitals have the equipment to perform neurotrauma and when it was last used. The study also examined the outcome of those patients who had undergone an emergency neurosurgical procedure.
 
  Of the 149 regional and rural hospitals in NSW, 16 stored a Hudson brace, perforator, burr and Gigli saw sterile and ready to use in the operating theatre. Only one hospital utilised the equipment in the last year and 11 in the last 10 years. Of those patients who had undergone an emergency neurosurgical procedure, two patients died prior to transfer and three were confirmed deceased after transfer to a tertiary centre.
 
  The implementation of the NSW State Trauma Plan has streamlined the trauma triage process and transport of neurotrauma patients to regional and major trauma services. However, it is likely that knowledge of how to perform burr hole and craniectomy for the evacuation of extradural haematoma remains a useful skill for the rural surgeon and retrieval doctor if transport is delayed.
 The implementation of the NSW State Trauma Plan has streamlined the trauma triage process and transport of neurotrauma patients to regional and major trauma services. However, it is likely that knowledge of how to perform burr hole and craniectomy for the evacuation of extradural haematoma remains a useful skill for the rural surgeon and retrieval doctor if transport is delayed.