Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

Paediatric acute non-traumatic limp presenting to the emergency department: a retrospective observational study.

BACKGROUND: Acute non-traumatic limp in children has many causes, ranging from common benign and self-limiting disease to serious time-sensitive emergencies such as septic arthritis. We aimed to (1) describe the epidemiology and workup of paediatric acute non-traumatic limp presentation in three Australian EDs and (2) compare investigations and treatment between a tertiary paediatric centre and two non-tertiary centres. METHODS: A retrospective chart review of children aged 0-16 years, with an initial presentation of non-traumatic limp to three EDs in Melbourne, Australia. Data on presentation, management and outcomes was systematically collected on all eligible patients. RESULTS: Of 63 941 presentations over a 12-month period, 475 (0.7%) met inclusion criteria. The median (IQR) age of presentation was 5 (3-8) years, with a male predominance (61%). Blood tests and imaging were performed in 39% and 51%, respectively. 34% of presentations had no investigations. The most frequent ED diagnoses were transient synovitis (37%) and viral myositis (16%). 84% were discharged home after ED evaluation. Compared with the two non-tertiary hospitals, children who presented to the tertiary centre were less likely to have any investigation performed (OR=0.41, 95% CI: 0.27 to 0.62, p<0.001) and more likely to be discharged home after evaluation (OR=4.67, 95% CI: 2.79 to 7.81, p<0.001). CONCLUSION: Although mostly due to benign disorders, an important number of limping children who presented to the ED had serious disease, with approximately one-third of these not diagnosed at the initial ED visit. There is large variation in workup including blood test, imaging and decisions regarding ED disposition.

Outpatient parenteral antibiotic therapy (OPAT) for the management of bronchiectasis.

Background: Patients with bronchiectasis often require hospitalisation for the administration of intravenous antibiotics for the management of acute exacerbations. Increasingly, Outpatient Parenteral Antibiotic Therapy (OPAT) services have become available as a potential alternative for domiciliary management. Aims: This study assessed outcomes in both cystic fibrosis (CF) and non-CF bronchiectasis patients who received OPAT for the management of an acute exacerbation of bronchiectasis. Methods: A retrospective study of consecutive subjects was done in both CF and non-CF groups in a large metropolitan Health Service in Australia from 2016 to 2022. Results: There were 51 episodes of care in the non-CF group (22 subjects) and 73 episodes in the CF group (13 subjects). The non-CF group were nearly all treated with once daily domiciliary intravenous (IV) ceftriaxone (49/51 episodes) for a duration of 9.1 ± 3.0 days (mean and standard deviation (SD)) via a peripherally inserted venous canula (84% of episodes). In contrast, the CF group generally received dual IV antibiotics (64% of episodes), with an average duration of 16.8 ± 6.3 days via central venous access (100%). In the non-CF group, the admission rate to hospital after 1 month was 9.6% and in the CF group was 0%. At 3 and 6 months the readmission rate for the non-CF group was 15.7% and 19.6% and CF group was 21.9% and 31.5%. There was a low rate of complications for the OPAT admissions (2% for the non-CF group and 7% for CF group). Conclusions: OPAT is a viable alternative for the management of bronchiectasis exacerbations.

Pulmonary actinomycosis and polymicrobial empyema in a patient with ABPA and bronchocoele.

We present a 43-year-old woman, with a history of allergic bronchopulmonary aspergillosis and a chronic bronchocoele, who was admitted to hospital with an infection of the bronchocoele, progressing to a pulmonary abscess and polymicrobial empyema, following dental extraction and regular Lactobacillus probiotic ingestion. Interval chest imaging following this procedure demonstrated worsening right upper lobe opacities and a right-sided pleural effusion. Bronchoscopies identified copious mucoid secretions and an infected bronchocoele with a right upper lobe airways impaction. Oral cavity organisms including Actinomyces odontolyticus were cultured on bronchial washings. Streptococcus mitis and Lactobacillus rhamnosus were cultured in pleural fluid. Treatment with endoscopic mucoid secretion suctioning; intercostal catheter insertion and therapeutic drainage; and antibiotic, glucocorticoid and anti-IgE therapy resulted in clinical and radiological improvement. Our case illustrates the potential pulmonary complications from oral cavity organisms following tooth extraction and probiotic use in patients with chronic lung disease associated with mucoid lesions and airways obstruction.

Test characteristics of history, examination and investigations in the evaluation for septic arthritis in the child presenting with acute non-traumatic limp. A systematic review.

BACKGROUND: Septic arthritis is an uncommon but potentially significant diagnosis to be considered when a child presents to the emergency department (ED) with non-traumatic limp. Our objective was to determine the diagnostic accuracy of clinical findings (history and examination) and investigation results (pathology tests and imaging) for the diagnosis of septic arthritis among children presenting with acute non-traumatic limp to the ED. METHODS: Systematic review of the literature published between 1966 and June 2019 on MEDLINE and EMBASE databases. Studies were included if they evaluated children presenting with lower limb complaints and evaluated diagnostic performance of items from history, physical examination, laboratory testing or radiological examination. Data were independently extracted by two authors, and quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. RESULTS: 18 studies were identified, and included 2672 children (560 with a final diagnosis of septic arthritis). There was substantial heterogeneity in inclusion criteria, study setting, definitions of specific variables and the gold standard used to confirm septic arthritis. Clinical and investigation findings were reported using varying definitions and cut-offs, and applied to differing study populations. Spectrum bias and poor-to-moderate study design quality limit their applicability to the ED setting.Single studies suggest that the presence of joint tenderness (n=189; positive likelihood ratio 11.4 (95% CI 5.9 to 22.0); negative likelihood ratio 0.2 (95% CI 0.0 to 1.2)) and joint effusion on ultrasound (n=127; positive likelihood ratio 8.4 (95% CI 4.1 to 17.1); negative likelihood ratio 0.2 (95% CI 0.1 to 0.3)) appear to be useful. Two promising clinical risk prediction tools were identified, however, their performance was notably lower when tested in external validation studies. DISCUSSION: Differentiating children with septic arthritis from non-emergent disorders of non-traumatic limp remains a key diagnostic challenge for emergency physicians. There is a need for prospectively derived and validated ED-based clinical risk prediction tools.