Partial Scapholunate Interosseous Ligament Injuries: A Systematic Review of Treatment Options.

Purpose This systematic review summarizes the existing evidence on treatment options and outcomes for partial scapholunate interosseous ligament (pSLIL) injuries. Methods A systematic electronic search of Medline, Embase, and CINAHL was performed from inception through to February 13, 2022. All primary research articles addressing the treatment of pSLIL tears were eligible for inclusion regardless of timing of surgery, surgical technique, or rehabilitation. The PRISMA Checklist guided the reporting and data abstraction. Descriptive statistics and forest plots are presented. Results A total of 14 studies with 342 patients were included for analysis. Treatments were categorized into four groups: electrothermal shrinkage (ES), arthroscopic capsuloplasty (AC), open capsulodesis (OC), and no treatment (NT). There were five studies in the ES group ( N = 69, mean age = 34.3 ± 3.3 years), three studies in the AC group ( N = 138, mean age = 32.2 ± 3.8 years), five studies in the OC group ( N = 123, mean age of 30.7 ± 7.8 years), and one study in the NT group ( N = 12, mean age = 43 years, range = 28-67 years). The average postintervention visual analog scale pain score for the ES group was 1.4 ± 0.5 (from 5.7 ± 1.8), for the AC group was 3.2 ± 1.3 (from 6.6 ± 0), for the OC group was 2.3 ± 2.1 (from 5.6 ± 1.6), and for the NT group was 3.2 (from 7.6). The wrist extension range of motion improved postoperatively for all intervention groups (ES = 66.3°-70.7°; AC = 67°-74.5°; and OC = 48.9°-63.5°), whereas it remained unchanged for the NT group (46°-45°). Grip strength also improved in all intervention groups (ES = 17.9-29.9 kg; AC = 24.0-32.2 kg; and OC = 15.8-26.6 kg), while the NT group remained unchanged (25-24 kg). The radiographic scapholunate gap improved postoperatively in all groups that reported pre- and postintervention (ES = 2.2-1.9 mm; OC = 2.5-1.8 mm) and slightly worsened in the NT group (2.5-2.7 mm). In the ES group, there were three complications (11.5%, no major complications), in the AC group there was one major complication (0.9%, complex regional pain syndrome [CRPS]), and in the OC group there were six complications (15.4%, four major complications-CRPS). Conclusion All interventional treatment options (ES, AC, and OC) provided significant improvements in patient-reported pain, range of motion, grip strength, and radiographic parameters, with low complication rates. In comparison, no improvement in range of motion or grip strength was noted in the NT group. Therefore, surgical management of pSLIL injuries is an effective and relatively safe treatment option. Further studies comparing the outcomes of specific surgical treatments are warranted to further elucidate the optimal management option for pSLIL tears. Level of Evidence Level III, systematic review of Level III-IV studies.

Complexes of tubulin oligomers and tau form a viscoelastic intervening network cross-bridging microtubules into bundles.

The axon-initial-segment (AIS) of mature neurons contains microtubule (MT) fascicles (linear bundles) implicated as retrograde diffusion barriers in the retention of MT-associated protein (MAP) tau inside axons. Tau dysfunction and leakage outside of the axon is associated with neurodegeneration. We report on the structure of steady-state MT bundles in varying concentrations of Mg2+ or Ca2+ divalent cations in mixtures containing αß-tubulin, full-length tau, and GTP at 37 °C in a physiological buffer. A concentration-time kinetic phase diagram generated by synchrotron SAXS reveals a wide-spacing MT bundle phase (Bws), a transient intermediate MT bundle phase (Bint), and a tubulin ring phase. SAXS with TEM of plastic-embedded samples provides evidence of a viscoelastic intervening network (IN) of complexes of tubulin oligomers and tau stabilizing MT bundles. In this model, αß-tubulin oligomers in the IN are crosslinked by tau's MT binding repeats, which also link αß-tubulin oligomers to αß-tubulin within the MT lattice. The model challenges whether the cross-bridging of MTs is attributed entirely to MAPs. Tubulin-tau complexes in the IN or bound to isolated MTs are potential sites for enzymatic modification of tau, promoting nucleation and growth of tau fibrils in tauopathies.

Camouflaged angiogenic BMP-2 functions exposed by pico-paracrine biohybrids.

The constant release of human bone morphogenetic protein 2 (rhBMP-2) in the picomolar range (Pico-Stat) from PDLLA-biohybrids led to the detection of intrinsic novel pro- and anti-angiogenic functions of this cytokine. As integrant part in this perspective of previous work, first evidence for the binding of rhBMP-2, as an inverse agonist, to allosteric angiogenic receptors in cocultures of human endothelial cells is reported.

Crystal structures of multidrug efflux transporters from Burkholderia pseudomallei suggest details of transport mechanism.

BpeB and BpeF are multidrug efflux transporters from Burkholderia pseudomallei that enable multidrug resistance. Here, we report the crystal structures of BpeB and BpeF at 2.94 Å and 3.0 Å resolution, respectively. BpeB was found as an asymmetric trimer, consistent with the widely-accepted functional rotation mechanism for this type of transporter. One of the monomers has a distinct structure that we interpret as an intermediate along this functional cycle. Additionally, a detergent molecule bound in a previously undescribed binding site provides insights into substrate translocation through the pathway. BpeF shares structural similarities with the crystal structure of OqxB from Klebsiella pneumoniae, where both are symmetric trimers composed of three "binding"-state monomers. The structures of BpeB and BpeF further our understanding of the functional mechanisms of transporters belonging to the HAE1-RND superfamily.

Exploring Cefiderocol Resistance Mechanisms in Burkholderia pseudomallei.

Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by ß-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with in vitro resistance found in a few isolates. Resistance in clinical B. pseudomallei isolates from Australia is caused by a hitherto uncharacterized mechanism. We show that, like in other Gram-negatives, the PiuA outer membrane receptor plays a major role in cefiderocol nonsusceptibility in isolates from Malaysia.

A multiple comorbidities mouse lung infection model in ApoE­deficient mice.

Acute pneumonia is characterised by a period of intense inflammation. Inflammation is now considered to be a key step in atherosclerosis progression. In addition, pre-existing atherosclerotic inflammation is considered to play a role in pneumonia progression and risk. In the present study, a multiple comorbidities murine model was used to study respiratory and systemic inflammation that results from pneumonia in the setting of atherosclerosis. Firstly, a minimal infectious dose of Streptococcus pneumoniae (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 ApoE -/- mice were fed a high-fat diet prior to administering intranasally 105 colony forming units of TIGR4 or phosphate-buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by magnetic resonance imaging (MRI) and positron emission tomography (PET). Mice were euthanised and investigated for changes in lung morphology and changes in systemic inflammation using ELISA, Luminex assay and real-time PCR. TIGR4-inoculated mice presented with varying degrees of lung infiltrate, pleural effusion and consolidation on MRI at all time points up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4-inoculated mice up to 28 days PI. The majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4-inoculated mice displayed significantly increased inflammatory gene expression [interleukin (IL)-1ß and IL-6] in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7 and 28 days PI respectively. The mouse model developed by the authors presents a discovery tool to understand the link between inflammation related to acute infection such as pneumonia and increased risk of cardiovascular disease observed in humans.

A conserved active site PenA ß-lactamase Ambler motif specific for Burkholderia pseudomallei/B. mallei is likely responsible for intrinsic amoxicillin-clavulanic acid sensitivity and facilitates a simple diagnostic PCR assay for melioidosis.

Burkholderia pseudomallei is a soil- and water-dwelling Gram-negative bacterium that causes melioidosis in humans and animals. Amoxicillin-clavulanic acid (AMC) susceptibility has been hailed as an integral part of the screening algorithm for identification of B. pseudomallei, but the molecular basis for the inherent AMC susceptibility of this bacterium remains undefined. This study showed that B. pseudomallei (and the closely-related B. mallei) wild-type strains are the only Burkholderia spp. that contain a 70STSK73 PenA Ambler motif. This motif was present in >99.5% of 1820 analysed B. pseudomallei strains and 100% of 83 analysed B. mallei strains, and is proposed as the likely cause for their inherent AMC sensitivity. The authors developed a polymerase chain reaction (PCR) assay that specifically amplifies the penA70ST(S/F)K73-containing region from B. pseudomallei and B. mallei, but not from the remaining B. pseudomallei complex species or the 70STFK73 region from the closely-related penB of B. cepacia complex species. The abundance and purity of the 193-bp PCR fragment from putative B. pseudomallei isolates from clinical and environmental samples is likely sufficient for reliable confirmation of the presence of B. pseudomallei. The PCR assay is designed to be especially suited for use in resource-constrained areas. While not further explored in this study, the assay may allow diagnosis of putative B. mallei in culture isolates from animal and human samples.

Cognitive Behavioral Therapy for Insomnia Among Active Duty Military Personnel Diagnosed With Obstructive Sleep Apnea.

INTRODUCTION: Insomnia and obstructive sleep apnea are common conditions among military service members, with high rates of comorbidity. Although cognitive behavioral therapy for insomnia (CBT-I) has been established as an effective treatment for insomnia, it is unclear whether or not CBT-I is effective among service members with comorbid insomnia and obstructive sleep apnea. MATERIALS AND METHODS: This retrospective, observational study examined insomnia outcomes among a group of service member patients (N = 73) with comorbid insomnia and obstructive sleep apnea. All patients received individual CBT-I in a specialty sleep clinic at a military treatment facility. Seven outcomes associated with insomnia were evaluated before and after treatment. RESULTS: On average, patients showed significant improvement in sleep onset latency, wake after sleep onset, sleep efficiency, number of awakenings, and symptoms reported on the Insomnia Severity Index. Twenty-six percent of patients showed clinically significant improvement in reported insomnia symptoms. CONCLUSIONS: These results suggest that CBT-I may be effective in treating military service members with comorbid insomnia and obstructive sleep apnea. Despite the limitations of data collected in a clinical setting, consistent findings across five of the seven outcome measures provide good evidence that this treatment can be implemented in military settings.

Antagonistic activity of Lactiplantibacillus plantarum 6.2 extracted from cocoa fermentation and its supernatant on Gardnerella vaginalis.

Search for alternative methods for the treatment of bacterial vaginosis has been growing, and probiotics being among them. The most well-known probiotic microorganisms are lactobacilli, which are naturally present in the vaginal microenvironment. Cocoa fermentation is a source of lactic acid bacteria, with lactobacilli being the most prominent. The aim of this study was to evaluate the antagonistic activity of Lactiplantibacillus plantarum 6.2 a strain of lactobacilli isolated from cocoa fermentation, and its cell-free supernatant on Gardnerella vaginalis. It was shown that Lpb. plantarum 6.2 and its supernatant, used at three concentrations, i.e., 40, 20 and 10 mg/mL, have a strong antagonistic activity against G. vaginalis, with a probable action of proteinaceous bacteriocins; the activity was lost after heat treatment. The ability to exclude and displace G. vaginalis from the adhesion site to vaginal HMVII epithelial cells was also demonstrated by the lactobacilli and the supernatant, with the latter showing a bactericidal effect. Thus, the Lpb. plantarum 6.2 strain presents itself as a good probiotic with potential to be used not only as a therapeutic alternative for vaginosis but also as a complement to existing therapies.

Evaluation of Delafloxacin against a Burkholderia pseudomallei Efflux Mutant Panel.

In vitro activities of delafloxacin and ciprofloxacin were evaluated against Burkholderia pseudomallei mutants expressing or lacking defined resistance-nodulation-cell division (RND) efflux pumps using CLSI methodology at pHs of 5.8 and 7.2. Delafloxacin MIC values were as much as 8-fold lower at pH 5.8 than those at pH 7.2, while ciprofloxacin MICs increased as much as 8-fold. The data from this study suggest that compared to ciprofloxacin, delafloxacin may have improved efflux avoidance, notably at acidic pH. In contrast to ciprofloxacin, delafloxacin may thus retain its therapeutic potential, even in BpeEF-OprC efflux-pump-expressing B. pseudomallei strains that compromise the use of fluoroquinolones, such as ciprofloxacin. IMPORTANCE Resistance-nodulation-cell division (RND) efflux pumps play a major role in intrinsic and acquired antibiotic resistance in Burkholderia pseudomallei, and these pumps are its only known multidrug resistance determinants. Fluoroquinolones have performed poorly in clinical settings and are currently not recommended for treatment of B. pseudomallei infections. While the reasons for the poor clinical performance of this pathogen remain unclear, efflux may be partially responsible since fluoroquinolones like ciprofloxacin are prone to efflux by RND pumps, notably BpeEF-OprC. In vitro efficacy testing using a panel of efflux-proficient and efflux-deficient strains allows identification of fluoroquinolones that compared to ciprofloxacin are less prone to efflux.

Bilateral Preiser Disease in a Patient with Sickle Cell Anemia.

Preiser disease is a rare condition of avascular necrosis of the scaphoid occurring in the absence scaphoid fracture or trauma. While the etiology of Preiser disease remains unknown, it has been associated with steroid use, chemotherapy, and infrequently with systemic diseases. No reports have associated Preiser disease with hemoglobinopathy. Due to the rarity of Preiser disease, management remains controversial and evidence is limited. Here, we describe the case of a 32-year-old right-hand dominant male with sickle cell anemia and a 4-year history of bilateral wrist pain. Radiographs and gadolinium-enhanced magnetic resonance imaging revealed bilateral Preiser disease. He was successfully managed with a 1,2 intercompartmental supraretinicaular artery vascularized bone graft to the right scaphoid.

Anatomical Study of the Innervation of Triangular Fibrocartilage Complex and Distal Radioulnar and Radiocarpal Joints: Implications for Denervation.

PURPOSE: Open and percutaneous denervation is an emerging technique for joint pain. This study investigated the course and distribution of the articular branches innervating the triangular fibrocartilage complex (TFCC), distal radioulnar joint (DRUJ), and radiocarpal joint (RCJ) relative to bony and soft tissue landmarks to guide wrist denervation procedures. METHODS: Fourteen formalin-embalmed specimens were serially dissected to expose the origin, course, and distribution of articular branches innervating the TFCC, DRUJ, and RCJ. Bony and soft tissue landmarks to localize each articular branch were documented and visualized on a 3-dimensional reconstruction of the bones of the distal forearm and hand. RESULTS: The TFCC was innervated by articular branches from the posterior interosseus nerve (10 of 14 specimens), dorsal cutaneous branch of the ulnar nerve (14 of 14 specimens), palmar cutaneous branch of the ulnar nerve (12 of 14 specimens), and medial antebrachial cutaneous nerve (9 of 14 specimens). The DRUJ was innervated by the posterior interosseus nerve (9 of 14 specimens) and anterior interosseus nerve (14 of 14 specimens). The RCJ was innervated by the posterior interosseus nerve (14 of 14 specimens), superficial branch of the radial nerve (5 of 14 specimens), lateral antebrachial cutaneous nerve (14 of 14 specimens), and palmar cutaneous branch of the median nerve (10 of 14 specimens). CONCLUSIONS: Multiple nerves were found to innervate the TFCC, DRUJ, and RCJ. The relationship of anatomical landmarks to specific articular branches supplying the TFCC, DRUJ, and RCJ can inform selective denervation procedures based on the structural origin of pain. CLINICAL RELEVANCE: The detailed documentation of the spatial relationship of the nerve supply to the wrist provides clinicians with the anatomical basis to optimize current, and develop new denervation protocols to manage chronic wrist pain.

Cardiovascular changes after pneumonia in a dual disease mouse model.

Residual inflammation in cardiovascular organs is thought to be one of the catalysts for the increased risk of cardiovascular complications seen following pneumonia. To test this hypothesis, we investigated changes in plaque characteristics and inflammatory features in ApoE-/- mouse aorta and heart following pneumonia. Male ApoE-/- mice were fed a high fat diet for 8 weeks before intranasal inoculation with either Streptococcus pneumoniae serotype 4 (test group) or phosphate buffered saline (control group). Mice were sacrificed at 2-, 7- and 28-days post-challenge. Changes in plaque burden and characteristics in aortic root and thoracic aorta were characterized by Oil red O and Trichrome stains. Inflammatory changes were investigated by FDG-PET imaging and immunofluorescence staining. We found TIGR4-infected mice present with increased plaque presence in the aortic root and thoracic aorta at 2- and 28-days post-inoculation, respectively. Aortic wall remodelling was also more pronounced in mice challenged with pneumococci at 28 days post-inoculation. Aortic root plaques of infected mice had reduced collagen and smooth muscle cells, consistent with an unstable plaque phenotype. Pneumonia alters plaque burden, plaque characteristics, and aortic wall remodelling in ApoE-/- mice. These effects caused by Streptococcus pneumoniae TIGR4, may contribute to the increased risk of cardiovascular complications seen in survivors of this infection.

Proteomic Signatures of Antimicrobial Resistance in Yersinia pestis and Francisella tularensis.

Antimicrobial resistance (AMR) is a well-recognized, widespread, and growing issue of concern. With increasing incidence of AMR, the ability to respond quickly to infection with or exposure to an AMR pathogen is critical. Approaches that could accurately and more quickly identify whether a pathogen is AMR also are needed to more rapidly respond to existing and emerging biological threats. We examined proteins associated with paired AMR and antimicrobial susceptible (AMS) strains of Yersinia pestis and Francisella tularensis, causative agents of the diseases plague and tularemia, respectively, to identify whether potential existed to use proteins as signatures of AMR. We found that protein expression was significantly impacted by AMR status. Antimicrobial resistance-conferring proteins were expressed even in the absence of antibiotics in growth media, and the abundance of 10-20% of cellular proteins beyond those that directly confer AMR also were significantly changed in both Y. pestis and F. tularensis. Most strikingly, the abundance of proteins involved in specific metabolic pathways and biological functions was altered in all AMR strains examined, independent of species, resistance mechanism, and affected cellular antimicrobial target. We have identified features that distinguish between AMR and AMS strains, including a subset of features shared across species with different resistance mechanisms, which suggest shared biological signatures of resistance. These features could form the basis of novel approaches to identify AMR phenotypes in unknown strains.

Transmission of Antimicrobial Resistant Yersinia pestis During a Pneumonic Plague Outbreak.

BACKGROUND: Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy. METHODS: A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current recommended first-line treatment in Madagascar, was retrospectively characterized using epidemiology, clinical diagnostics, molecular characterization, and animal studies. RESULTS: The outbreak occurred in February 2013 in the Faratsiho district of Madagascar and involved 22 cases, including 3 untreated fatalities. The 19 other cases participated in funeral practices for the fatal cases and fully recovered after combination antimicrobial therapy: intramuscular streptomycin followed by oral co-trimoxazole. The Y. pestis strain that circulated during this outbreak is resistant to streptomycin resulting from a spontaneous point mutation in the 30S ribosomal protein S12 (rpsL) gene. This same mutation causes streptomycin resistance in 2 unrelated Y. pestis strains, one isolated from a fatal PP case in a different region of Madagascar in 1987 and another isolated from a fatal PP case in China in 1996, documenting this mutation has occurred independently at least 3 times in Y. pestis. Laboratory experiments revealed this mutation has no detectable impact on fitness or virulence, and revertants to wild-type are rare in other species containing it, suggesting Y. pestis strains containing it could persist in the environment. CONCLUSIONS: Unique antimicrobial resistant (AMR) strains of Y. pestis continue to arise in Madagascar and can be transmitted during PP outbreaks.

Expanding the Burkholderia pseudomallei Complex with the Addition of Two Novel Species: Burkholderia mayonis sp. nov. and Burkholderia savannae sp. nov.

Distinct Burkholderia strains were isolated from soil samples collected in tropical northern Australia (Northern Territory and the Torres Strait Islands, Queensland). Phylogenetic analysis of 16S rRNA and whole genome sequences revealed these strains were distinct from previously described Burkholderia species and assigned them to two novel clades within the B. pseudomallei complex (Bpc). Because average nucleotide identity and digital DNA-DNA hybridization calculations are consistent with these clades representing distinct species, we propose the names Burkholderia mayonis sp. nov. and Burkholderia savannae sp. nov. Strains assigned to B. mayonis sp. nov. include type strain BDU6T (=TSD-80; LMG 29941; ASM152374v2) and BDU8. Strains assigned to B. savannae sp. nov. include type strain MSMB266T (=TSD-82; LMG 29940; ASM152444v2), MSMB852, BDU18, and BDU19. Comparative genomics revealed unique coding regions for both putative species, including clusters of orthologous genes associated with phage. Type strains of both B. mayonis sp. nov. and B. savannae sp. nov. yielded biochemical profiles distinct from each other and from other species in the Bpc, and profiles also varied among strains within B. mayonis sp. nov. and B. savannae sp. nov. Matrix-assisted laser desorption ionization time-of-flight (MLST) analysis revealed a B. savannae sp. nov. cluster separate from other species, whereas B. mayonis sp. nov. strains did not form a distinct cluster. Neither B. mayonis sp. nov. nor B. savannae sp. nov. caused mortality in mice when delivered via the subcutaneous route. The addition of B. mayonis sp. nov. and B. savannae sp. nov. results in a total of eight species currently within the Bpc. IMPORTANCEBurkholderia species can be important sources of novel natural products, and new species are of interest to diverse scientific disciplines. Although many Burkholderia species are saprophytic, Burkholderia pseudomallei is the causative agent of the disease melioidosis. Understanding the genomics and virulence of the closest relatives to B. pseudomallei, i.e., the other species within the B. pseudomallei complex (Bpc), is important for identifying robust diagnostic targets specific to B. pseudomallei and for understanding the evolution of virulence in B. pseudomallei. Two proposed novel species, B. mayonis sp. nov. and B. savannae sp. nov., were isolated from soil samples collected from multiple locations in northern Australia. The two proposed species belong to the Bpc but are phylogenetically distinct from all other members of this complex. The addition of B. mayonis sp. nov. and B. savannae sp. nov. results in a total of eight species within this significant complex of bacteria that are available for future studies.

Outcomes from Returning Individual versus Only Study-Wide Biomonitoring Results in an Environmental Exposure Study Using the Digital Exposure Report-Back Interface (DERBI).

BACKGROUND: Study participants want to receive their biomonitoring results for environmental chemicals, and ethics guidelines encourage reporting back. However, few studies have quantitively assessed participants' responses to individual exposure reports, and digital methods have not been evaluated. OBJECTIVES: We isolated effects of receiving personal results vs. only study-wide findings and investigated whether effects differed for Black participants. METHODS: We randomly assigned a subset of 295 women from the Child Health and Development Studies, half of whom were Black, to receive a report with personal environmental chemical results or only study-wide (aggregate) findings. Reports included results for 42 chemicals and lipids and were prepared using the Digital Exposure Report-Back Interface (DERBI). Women were interviewed before and after viewing their report. We analyzed differences in website activity, emotional responses, and intentions to participate in future research by report type and race using Wilcoxon rank sum tests, Wilcoxon-Pratt signed ranks tests, and multiple regression. RESULTS: The personal report group spent approximately twice as much time on their reports as the aggregate group before the post-report-back interview. Among personal-report participants (n=93), 84% (78) viewed chemical group information for at least one personal result highlighted on their home page; among aggregate-report participants (n=94), 66% (62) viewed any chemical group page. Both groups reported strong positive feelings (curious, informed, interested, respected) about receiving results before and after report-back and mild negative feelings (helpless, scared, worried). Although most participants remained unworried after report-back, worry increased by a small amount in both groups. Among Black participants, higher post report-back worry was associated with having high levels of chemicals. CONCLUSIONS: Participants were motivated by their personal results to access online information about chemical sources and potential health effects. Report-back was associated with a small increase in worry, which could motivate appropriate action. Personal report-back increased engagement with exposure reports among Black participants. https://doi.org/10.1289/EHP9072.

The Pseudomonas aeruginosa whole genome sequence: A 20th anniversary celebration.

Toward the end of August 2000, the 6.3 Mbp whole genome sequence of Pseudomonas aeruginosa strain PAO1 was published. With 5570 open reading frames (ORFs), PAO1 had the largest microbial genome sequenced up to that point in time-including a large proportion of metabolic, transport and antimicrobial resistance genes supporting its ability to colonize diverse environments. A remarkable 9% of its ORFs were predicted to encode proteins with regulatory functions, providing new insight into bacterial network complexity as a function of network size. In this celebratory article, we fast forward 20 years, and examine how access to this resource has transformed our understanding of P. aeruginosa. What follows is more than a simple review or commentary; we have specifically asked some of the leaders in the field to provide personal reflections on how the PAO1 genome sequence, along with the Pseudomonas Community Annotation Project (PseudoCAP) and Pseudomonas Genome Database (pseudomonas.com), have contributed to the many exciting discoveries in this field. In addition to bringing us all up to date with the latest developments, we also ask our contributors to speculate on how the next 20 years of Pseudomonas research might pan out.

Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque.

Acute coronary syndrome (ACS) describes a range of conditions associated with the rupture of high-risk or vulnerable plaque. Vulnerable atherosclerotic plaque is associated with many changes in its microenvironment which could potentially cause rapid plaque progression. Present-day PET imaging presents a plethora of radiopharmaceuticals designed to image different characteristics throughout plaque progression. Improved knowledge of atherosclerotic disease pathways has facilitated a growing number of pathophysiological targets for more innovative radiotracer design aimed at identifying at-risk vulnerable plaque and earlier intervention opportunity. This paper reviews the efficacy of PET imaging radiotracers 18F-FDG, 18F-NaF, 68Ga-DOTATATE, 64Cu-DOTATATE and 68Ga-pentixafor in plaque characterisation and risk assessment, as well as the translational potential of novel radiotracers in animal studies. Finally, we discuss our murine PET imaging experience and the challenges encountered.