The formyl peptide fMLF primes platelet activation and augments thrombus formation

Formyl peptide receptors (FPRs) play pivotal roles in the regulation of innate immunity and host defence. FPRs include three family members; FPR1, FPR2/ALX and FPR3. The activation of FPR1 by its high affinity ligand, N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLF) (a bacterial chemoattractant peptide), triggers intracellular signalling in immune cells such as neutrophils and exacerbates inflammatory responses to accelerate the clearance of microbial infection. Notably, fMLF has been demonstrated to induce intracellular calcium mobilisation and chemotaxis in platelets that are known to play significant roles in the regulation of innate immunity and inflammatory responses. Despite a plethora of research focused on the roles of FPR1 and its ligands such as fMLF on the modulation of immune responses, their impact on the regulation of haemostasis and thrombosis remains unexplored

Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

<i>Pseudomonas aeruginosa</i> in Nepali hospitals: poor outcomes amid 10 years of increasing antimicrobial resistance

ObjectiveTo determine antimicrobial resistance patterns and prevalence of multi- (MDR, i.e., resistant to ⩾3 classes of antimicrobial agents) and extensively (XDR, i.e., resistant to ⩾3, susceptible to ⩽2 groups of antibiotics) drug-resistant strains of Pseudomonas aeruginosa.MethodsThis was a cross-sectional study conducted in Nepal Mediciti Hospital, Lalitpur, Nepal, using standard microbiological methods with Kirby Bauer disc diffusion to identify antimicrobial susceptibility.ResultsP. aeruginosa (n = 447) were most frequently isolated in respiratory (n = 203, 45.4%) and urinary samples (n = 120, 26.8%). AWaRe Access antibiotics showed 25-30% resistance, Watch antibiotics 30-55%. Susceptibility to AWaRe Reserve antibiotics remains high; however, 32.8% were resistant to aztreonam. Overall, 190 (42.5%) were MDR and 99 (22.1%) XDR (first Nepali report) based on mainly non-respiratory samples. The majority of infected patients were >40 years (n = 229, 63.2%) or inpatients (n = 181, 50.0%); 36 (15.2%) had an unfavourable outcome, including death (n = 25, 10.5%). Our larger study showed a failure of improvement over eight previous studies covering 10 years.ConclusionAntibiotic resistance in P. aeruginosa occurred to all 19 AWaRe group antibiotics tested. Vulnerable patients are at significant risk from such resistant strains, with a high death rate. Sustainable and acceptable antibiotic surveillance and control are urgently needed across Nepal, as antimicrobial resistance has deteriorated over the last decade

High antibiotic resistance and mortality with <i>Acinetobacter</i> species in a tertiary hospital, Nepal

SettingNepal Mediciti Hospital, Bhainsepati, Lalitpur, Nepal.ObjectivesTo determine antimicrobial resistance patterns, and the number and proportion of multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) cases among all patients with Acinetobacter isolates between September 2018 and September 2019.DesignThis was a hospital laboratory-based, cross-sectional study.ResultsAcinetobacter spp. (n = 364) were more common in respiratory (n = 172, 47.3%) and invasive samples such as blood, body fluids (n = 95, 26.1%). Sensitivity to AWaRe (Access, Watch and Reserve) Group antibiotics (tigecycline, polymyxin B, colistin) remained high. MDR (resistance to at least three classes of antimicrobial agents) (n = 110, 30.2%) and XDR (MDR plus carbapenem) (n = 87, 23.9%) isolates were most common in the Watch Group of antibiotics and found in respectively 99 (31.0%) and 78 (24.5%) patients (n = 319). Infected patients were more likely to be aged >40 years (n = 196, 61.4%) or inpatients (n = 191, 59.9%); 76 (23.8%) patients had an unfavourable outcome, including death (n = 59, 18.5%).ConclusionA significant proportion of MDR and XDR isolates was found; nearly one patient in five died. Robust hospital infection prevention and control measures (particularly for respiratory and invasive procedures) and routine surveillance are needed to reduce infections and decrease the mortality rate. Tigecycline, polymyxin B and colistin should be cautiously used only in MDR and XDR cases

Primordial Black Holes: sirens of the early Universe

Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

Pharmacists in Pharmacovigilance: Can Increased Diagnostic Opportunity in Community Settings Translate to Better Vigilance?

The pharmacy profession has undergone substantial change over the last two to three decades. Whilst medicine supply still remains a central function, pharmacist’s roles and responsibilities have become more clinic and patient focused. In the community (primary care), pharmacists have become important providers of healthcare as Western healthcare policy advocates patient self-care. This has resulted in pharmacists taking on greater responsibility in managing minor illness and the delivery of public health interventions. These roles require pharmacists to more fully use their clinical skills, and often involve diagnosis and therapeutic management. Community pharmacists are now, more than ever before, in a position to identify, record and report medication safety incidents. However, current research suggests that diagnostic ability of community pharmacists is questionable and they infrequently report to local or national schemes. The aim of this paper is to highlight current practice and suggest ways in which community pharmacy can more fully contribute to patient safety