The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Properties of Neon, Magnesium, and Silicon Primary Cosmic Rays Results from the Alpha Magnetic Spectrometer

We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8 x 10(6) Ne, 2.2 x 10(6) Mg, and 1.6 x 10(6) Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays

Towards Understanding the Origin of Cosmic-Ray Positrons

Precision measurements of cosmic ray positrons are presented up to 1 TeV based on 1.9 million positrons collected by the Alpha Magnetic Spectrometer on the International Space Station. The positron flux exhibits complex energy dependence. Its distinctive properties are (a) a significant excess starting from 25.2 +/- 1.8 GeV compared to the lower-energy, power-law trend, (b) a sharp dropoff above 284(-64)(+91) GeV, (c) in the entire energy range the positron flux is well described by the sum of a term associated with the positrons produced in the collision of cosmic rays, which dominates at low energies, and a new source term of positrons, which dominates at high energies, and (d) a finite energy cutoff of the source term of E-s = 810(-180)(+310) GeV is established with a significance of more than 4 sigma. These experimental data on cosmic ray positrons show that, at high energies, they predominantly originate either from dark matter annihilation or from other astrophysical sources

Properties of Cosmic Helium Isotopes Measured by the Alpha Magnetic Spectrometer

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of He-3 and He-4 fluxes are presented. The measurements are based on 100 million He-4 nuclei in the rigidity range from 2.1 to 21 GV and 18 million He-3 from 1.9 to 15 GV collected from May 2011 to November 2017. We observed that the He-3 and He-4 fluxes exhibit nearly identical variations with time. The relative magnitude of the variations decreases with increasing rigidity. The rigidity dependence of the He-3/He-4 flux ratio is measured for the first time. Below 4 GV, the He-3/He-4 flux ratio was found to have a significant long-term time dependence. Above 4 GV, the He-3/He-4 flux ratio was found to be time independent, and its rigidity dependence is well described by a single power law proportional to R-Delta with Delta = 0.294 0.004. Unexpectedly, this value is in agreement with the B/O and B/C spectral indices at high energies

Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2 x 10(6) events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above similar to 700 GV. We observed that the nitrogen flux Phi(N) can be presented as the sum of its primary component Phi(P)(N) and secondary component Phi(S)(N), Phi(N) = Phi(P)(N) + Phi(S)(N), and we found Phi(N) is well described by the weighted sum of the oxygen flux Phi(O) (primary cosmic rays) and the boron flux Phi(B) (secondary cosmic rays), with Phi(P)(N) = (0.090 +/- 0.002) x Phi(O) and Phi(S)(N) = (0.62 +/- 0.02) x Phi(B) over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to < 30% above 1 TV

Properties of Iron Primary Cosmic Rays: Results from the Alpha Magnetic Spectrometer

We report the observation of new properties of primary iron (Fe) cosmic rays in the rigidity range 2.65 GV to 3.0 TV with 0.62 x 10(6) iron nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. Above 80.5 GV the rigidity dependence of the cosmic ray Fe flux is identical to the rigidity dependence of the primary cosmic ray He, C, and O fluxes, with the Fe/O flux ratio being constant at 0.155 +/- 0.006. This shows that unexpectedly Fe and He, C, and O belong to the same class of primary cosmic rays which is different from the primary cosmic rays Ne, Mg, and Si class

Properties of Heavy Secondary Fluorine Cosmic Rays: Results from the Alpha Magnetic Spectrometer

Precise knowledge of the charge and rigidity dependence of the secondary cosmic ray fluxes and the secondary-to-primary flux ratios is essential in the understanding of cosmic ray propagation. We report the properties of heavy secondary cosmic ray fluorine F in the rigidity R range 2.15 GV to 2.9 TV based on 0.29 million events collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The fluorine spectrum deviates from a single power law above 200 GV. The heavier secondary-to-primary F/Si flux ratio rigidity dependence is distinctly different from the lighter B/O (or B/C) rigidity dependence. In particular, above 10 GV, the F/Si/B/O ratio can be described by a power law R-delta with delta = 0.052 +/- 0.007. This shows that the propagation properties of heavy cosmic rays, from F to Si, are different from those of light cosmic rays, from He to O, and that the secondary cosmic rays have two classes

Towards Understanding the Origin of Cosmic-Ray Electrons

Precision results on cosmic-ray electrons are presented in the energy range from 0.5 GeV to 1.4 TeV based on 28.1 x 10(6) electrons collected by the Alpha Magnetic Spectrometer on the International Space Station. In the entire energy range the electron and positron spectra have distinctly different magnitudes and energy dependences. The electron flux exhibits a significant excess starting from 42.1(-5.2)(+5.4) GeV compared to the lower energy trends, but the nature of this excess is different from the positron flux excess above 25.2 +/- 1.8 GeV. Contrary to the positron flux, which has an exponential energy cutoff of 810(-180)(+310) GeV, at the 5 sigma level the electron flux does not have an energy cutoff below 1.9 TeV. In the entire energy range the electron flux is well described by the sum of two power law components. The different behavior of the cosmic-ray electrons and positrons measured by the Alpha Magnetic Spectrometer is clear evidence that most high energy electrons originate from different sources than high energy positrons