Cryo-EM characterization of the anydromuropeptide permease AmpG central to bacterial fitness and β-lactam antibiotic resistance.

Bacteria invest significant resources into the continuous creation and tailoring of their essential protective peptidoglycan (PG) cell wall. Several soluble PG biosynthesis products in the periplasm are transported to the cytosol for recycling, leading to enhanced bacterial fitness. GlcNAc-1,6-anhydroMurNAc and peptide variants are transported by the essential major facilitator superfamily importer AmpG in Gram-negative pathogens including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa.

Building permits-control of type IV pilus assembly by PilB and its cofactors.

Many bacteria produce type IV pili (T4P), surfaced-exposed protein filaments that enable cells to interact with their environment and transition from planktonic to surface-adapted states. T4P are dynamic, undergoing rapid cycles of filament extension and retraction facilitated by a complex protein nanomachine powered by cytoplasmic motor ATPases. Dedicated assembly motors drive the extension of the pilus fiber into the extracellular space, but like any machine, this process is tightly organized.

A Growth-Survival Trade-Off Along an Elevation Gradient Is Altered by Earthquake Disturbance in a Monodominant Southern Beech Forest.

Tree growth-survival relationships link two demographic processes that individually dictate the composition, structure and functioning of forest ecosystems. While these relationships vary intra-specifically, it remains unclear how this reflects environmental variation and disturbance. We examined the influence of a 700-m elevation gradient and an  = 6.

PilY1 regulates the dynamic architecture of the type IV pilus machine in Pseudomonas aeruginosa.

Type IV pili (T4P) produced by the pathogen Pseudomonas aeruginosa play a pivotal role in adhesion, surface motility, biofilm formation, and infection in humans. Despite the significance of T4P as a potential therapeutic target, key details of their dynamic assembly and underlying molecular mechanisms of pilus extension and retraction remain elusive, primarily due to challenges in isolating intact T4P machines from the bacterial cell envelope. Here, we combine cryo-electron tomography with subtomogram averaging and integrative modelling to resolve in-situ architectural details of the dynamic T4P machine in P.

Cryptate binding energies towards high throughput chelator design: metadynamics ensembles with cluster-continuum solvation.

A tiered forcefield/semiempirical/-GGA pipeline together with a thermodynamic scheme designed with error cancellation in mind was developed to calculate binding energies of [2.2.2] cryptate complexes of mono- and divalent cations.

The effects of chlorhexidine, povidone-iodine and vancomycin on growth and biofilms of pathogens that cause prosthetic joint infections: an in-vitro model.

Background: Chlorhexidine gluconate (CHG) and povidone-iodine (PI) are commonly used to prevent prosthetic joint infection (PJI) during total joint replacement; however, their effective concentrations and impact on biofilms are not well defined.

Aim: To determine: (1) the in-vitro minimum inhibitory concentration of CHG and PI against model PJI-causing organisms and clinical isolates; (2) their impact on biofilm formation; (3) whether there is a synergistic benefit to combining the two solutions; and (4) whether adding the antibiotic vancomycin impacts antiseptic activity.

Methods: We measured in-vitro growth and biofilm formation of Staphylococcus epidermidis, meticillin-sensitive and meticillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans, as well as recent clinical isolates, in the presence of increasing concentrations of CHG and/or PI.

Pilot study to evaluate a training programme for primary care physiotherapists in the assessment and management of benign paroxysmal positional vertigo.

Objective: This pilot study aimed to evaluate a training programme for primary care physiotherapists focused on the assessment and management of benign paroxysmal positional vertigo.

Methods: A six-month training programme and toolkit utilising the revised Standards for Quality Improvement Reporting Excellence ('SQUIRE 2.0') guidelines was developed to facilitate the learning of new knowledge and skills in the assessment and management of benign paroxysmal positional vertigo following Gagne's model of instructional design.

Medical record prompts improve the frequency and documentation of dizziness and driving conversations in the ENT balance clinic.

Background: Driving capacity is affected by vestibular disorders and the medications used to treat them. Driving is not considered during medical consultations, with 92 per cent of patients attending a centre for dizziness not discussing it with the doctor.

Objective: To investigate if medical record prompts facilitate dizziness and driving conversations in ENT balance clinics.

Injury Risk Functions for the Midsized Male Wrist and Elbow as a Result of Behind Shield Blunt Trauma.

Ballistic shields protect users from a variety of threats, including projectiles. Shield back-face deformation (BFD) is the result of the shield deflecting or absorbing a projectile and deforming toward the user. Back-face deformation can result in localized blunt loading to the upper extremity, where the shield is supported by the user.

Laxative use in adults with intellectual disabilities: development of prescribing guidelines.

Background: Constipation is overrepresented in people with intellectual disabilities. Around 40% of people with intellectual disabilities who died prematurely were prescribed laxatives. A quarter of people with intellectual disabilities are said to be on laxatives.

A genetic screen identifies a role for oprF in Pseudomonas aeruginosa biofilm stimulation by subinhibitory antibiotics.

Biofilms are surface-associated communities of bacteria that grow in a self-produced matrix of polysaccharides, proteins, and extracellular DNA (eDNA). Sub-minimal inhibitory concentrations (sub-MIC) of antibiotics induce biofilm formation, potentially as a defensive response to antibiotic stress. However, the mechanisms behind sub-MIC antibiotic-induced biofilm formation are unclear.

Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence.

Introduction: Fragile X syndrome (FXS) is the most common inherited cause of Intellectual Disability. There is a broad phenotype that includes deficits in cognition and behavioral changes, alongside physical characteristics. Phenotype depends upon the level of mutation in the (fragile X messenger ribonucleoprotein 1) gene.

Mathematical modelling and deep learning algorithms to automate assessment of single and digitally multiplexed immunohistochemical stains in tumoural stroma.

Whilst automated analysis of immunostains in pathology research has focused predominantly on the epithelial compartment, automated analysis of stains in the stromal compartment is challenging and therefore requires time-consuming pathological input and guidance to adjust to tissue morphometry as perceived by pathologists. This study aimed to develop a robust method to automate stromal stain analyses using 2 of the commonest stromal stains (SMA and desmin) employed in clinical pathology practice as examples. An effective computational method capable of automatically assessing and quantifying tumour-associated stromal stains was developed and applied on cores of colorectal cancer tissue microarrays.

Injury Risk for the Hand and Forearm Under Loading Representative of Behind Shield Blunt Trauma.

Ballistic shields protect users from a variety of threats, including projectiles. Shield back-face deformation (BFD) is the result of the shield absorbing energy from a projectile and deforming towards the user. Back-face deformation can result in localized blunt loading to the upper extremity, where the shield is supported by the user and may cause injury through behind armour blunt trauma (BABT) mechanisms.

The potential for medicinal cannabis to help manage challenging behaviour in people with intellectual disability: A perspective review.

Background: Around 2% of the population have intellectual disabilities. Over one-third people with intellectual disabilities (PwID) present with 'challenging behaviour', which nosologically and diagnostically is an abstract concept. Challenging behaviour is influenced by a range of bio-psycho-social factors in a population, which is unable to suitably comprehend and/or communicate concerns.

Central metabolism is a key player in E. coli biofilm stimulation by sub-MIC antibiotics.

Exposure of Escherichia coli to sub-inhibitory antibiotics stimulates biofilm formation through poorly characterized mechanisms. Using a high-throughput Congo Red binding assay to report on biofilm matrix production, we screened ~4000 E. coli K12 deletion mutants for deficiencies in this biofilm stimulation response.

Phage Therapy in the Management of Urinary Tract Infections: A Comprehensive Systematic Review.

Urinary tract infections (UTIs) are a problem worldwide, affecting almost half a billion people each year. Increasing antibiotic resistance and limited therapeutic options have led to the exploration of alternative therapies for UTIs, including bacteriophage (phage) therapy. This systematic review aims at evaluating the efficacy of phage therapy in treating UTIs.

'They're all individuals, none of them are on the same boat': barriers to weight management in general practice from the rural nurse perspective.

Aim: To explore nurses' experiences with, and barriers to, obesity healthcare in rural general practice.

Background: Obesity is a significant health risk worldwide, which can lead to many other physical and psychosocial health issues that contribute to a poor quality of life. Primary care is considered the most suitable context to deliver obesity management healthcare across the world, including New Zealand, which reportedly has 34% of all adults (and 51% Indigenous Māori) classed as obese.

Barriers to obesity health care in general practice from rural Waikato GP perspectives: A qualitative study.

Objective: Over 34% of New Zealand (NZ) adults are classed as obese, which reduces quality of life for many individuals. Those living in rural areas, high-deprivation communities, and indigenous Māori populations are more likely to experience obesity and related co-morbidities than other cohorts. General practice is positioned as most suitable to deliver effective weight management health care; however, little is understood about the rural general practitioner (GP) experience in NZ, despite having the majority of patients at high risk of developing obesity.

Nutrient Limitation Sensitizes to Vancomycin.

Traditional antibacterial screens rely on growing bacteria in nutrient-replete conditions which are not representative of the natural environment or sites of infection. Instead, screening in more physiologically relevant conditions may reveal novel activity for existing antibiotics. Here, we screened a panel of antibiotics reported to lack activity against the opportunistic Gram-negative bacterium, , under low-nutrient and low-iron conditions, and discovered that the glycopeptide vancomycin inhibited the growth of at low micromolar concentrations through its canonical mechanism of action, disruption of peptidoglycan crosslinking.