Multi-omics and imaging mass cytometry characterization of human kidneys to identify pathways and phenotypes associated with impaired kidney function.

Despite the recent advances in our understanding of the role of lipids, metabolites, and related enzymes in mediating kidney injury, there is limited integrated multi-omics data identifying potential metabolic pathways driving impaired kidney function. The limited availability of kidney biopsies from living donors with acute kidney injury has remained a major constraint. Here, we validated the use of deceased transplant donor kidneys as a good model to study acute kidney injury in humans and characterized these kidneys using imaging and multi-omics approaches. We noted consistent changes in kidney injury and inflammatory markers in donors with reduced kidney function. Neighborhood and correlation analyses of imaging mass cytometry data showed that subsets of kidney cells (proximal tubular cells and fibroblasts) are associated with the expression profile of kidney immune cells, potentially linking these cells to kidney inflammation. Integrated transcriptomic and metabolomic analysis of human kidneys showed that kidney arachidonic acid metabolism and seven other metabolic pathways were upregulated following diminished kidney function. To validate the arachidonic acid pathway in impaired kidney function we demonstrated increased levels of cytosolic phospholipase A2 protein and related lipid mediators (prostaglandin E2) in the injured kidneys. Further, inhibition of cytosolic phospholipase A2 reduced injury and inflammation in human kidney proximal tubular epithelial cells in vitro. Thus, our study identified cell types and metabolic pathways that may be critical for controlling inflammation associated with impaired kidney function in humans.

Factors associated with viral load non-suppression among treatment-experienced pre-teenage children living with HIV in Kenya: a nationwide population-based cohort study, 2015-2021.

Background: Viral load non-suppression (VLNS) in children is a major public health concern because of attendant HIV disease progression and risk of morbidity and mortality. Based on a nationally representative database we present estimates of the prevalence, trends and factors associated with VLNS in Kenyan pre-teenage children between 2015 and 2021. Methods: Kenya National AIDS & STI Control Program's (NASCOP) maintains an early infant diagnosis and viral load (EID/VL) database for all persons living with HIV who are enrolled in the country's primary care clinics for purposes of monitoring progress towards achievement of the 95% viral suppression goals. Participants were eligible if they were children living with HIV (CLHIV), on combination ART (cART) treatment, and ≤12 years old. The modified Mann-Kendall trend test for serially correlated data was used to identify VLNS trends. Generalized estimating equations (GEE) with a logit link was used to assess the effects of covariates on the odds of VLNS (VL ≥1,000 copies/mL) over repeated points in time, allowing for the correlation among the repeated measures. Findings: Between January 2015 and December 2021, 508,743 viral load tests were performed on samples collected from 109,682 pre-teenage children. The prevalence of VLNS decreased from 22.9% (95% CI 22.4-23.3) to 12.5% (95% CI 12.1-12.9), p < 0.0001, and mean age increased from 3.1 (4.2) to 8.0 (3.2) years in 2015 and 2021 respectively. A modified Mann-Kendall trend test for serially correlated data denotes a statistically significant decreasing trend (τ = -0.300, p < 0.0001) over the study period. In the multivariable GEE analysis adjusted for covariates, the odds of VLNS decreased by 11% per year during the study period, (GEE-aOR 0.89, 95% CI 0.88-0.90; p < 0.0001). Factors positively associated with VLNS were EFV/NVP-based first-line cART regimen (GEE-aOR 1.74, 95% CI 1.65-1.84, p < 0.0001), PI-based cART regimen (GEE-aOR 1.82, 95% CI 1.72-1.92, p < 0.0001), and children aged 1-3 years (toddlers) (GEE-aOR: 1.84, 95% CI 1.79-1.90, p < 0.0001). On the contrary, DTG-based cART regimen, were negatively associated with VLNS (GEE-aOR 0.70, 95% CI 0.65-0.75, p < 0.0001). Interpretation: There is a strong evidence of decreasing viremia between 2015 and 2021. To sustain the decreasing trend, accelerating the switch from the suboptimal EVP/NVP first-line regimen to optimised DTG regimen is warranted. Funding: U.S. President's Emergency Plan for AIDS Relief (PEPFAR) and Clinton Health Access Initiative (CHAI).

Morphine aggravates inflammatory, behavioral, and hippocampal structural deficits in septic rats.

Although pain and sepsis are comorbidities of intensive care units, reported data on whether pain control by opioid analgesics could alter inflammatory and end-organ damage caused by sepsis remain inconclusive. Here, we tested the hypothesis that morphine, the gold standard narcotic analgesic, modifies behavioral and hippocampal structural defects induced by sepsis in male rats. Sepsis was induced with cecal ligation and puncture (CLP) and behavioral studies were undertaken 24 h later in septic and/or morphine-treated animals. The induction of sepsis or exposure to morphine (7 mg/kg) elicited similar: (i) falls in systolic blood pressure, (ii) alterations in spatial memory and learning tested by the Morris water maze, and (iii) depression of exploratory behavior measured by the new object recognition test. These hemodynamic and cognitive defects were significantly exaggerated in septic rats treated with morphine compared with individual interventions. Similar patterns of amplified inflammatory (IL-1ß) and histopathological signs of hippocampal damage were noted in morphine-treated septic rats. Additionally, the presence of intact opioid receptors is mandatory for the induction of behavioral and hemodynamic effects of morphine because no such effects were observed when the receptors were blocked by naloxone. That said, our findings suggest that morphine provokes sepsis manifestations of inflammation and interrelated hemodynamic, behavioral, and hippocampal deficits.

Effects of nutrient pulses on exotic species shift from positive to neutral with decreasing water availability.

Temporal fluctuation in nutrient availability generally promotes the growth of exotic plant species and has been recognized as an important driver of exotic plant invasions. However, little is known about how the impact of fluctuating nutrients on exotic species is dependent on the availability of other resources, although most ecosystems are experiencing dramatic variations in a wide variety of resources due to global change and human disturbance. Here, we explored how water availability mediates the effect of nutrient pulses on the growth of six exotic and six native plant species. We subjected individual plants of exotic and native species to well watered or water stressed conditions. For each level of water availability, we added equivalent amounts of nutrients at a constant rate, as a single large pulse, or in multiple small pulses. Under well watered conditions, nutrient pulses promoted exotic plant growth relative to nutrients supplied constantly, while they had no significant effect on natives. In contrast, under water stressed conditions, water deficiency inhibited the growth of all exotic and native species. More importantly, nutrient pulses did not increase plant growth relative to nutrients supplied constantly and these phenomena were observed for both exotic and native species. Taken together, our study shows that the impact of fluctuating nutrient availability on the growth of exotic plant species strongly depends on the variation of other resources, and that the positive effect of nutrient pulses under well watered conditions disappears under water stressed conditions. Our findings suggest that the variation in multiple resources may have complex feedback on exotic plant invasions and, therefore, it is critical to encompass multiple resources for the evaluation of fluctuating resource availability effects on exotic plant species. This will allow us to project the invasive trajectory of exotic plant species more accurately under future global change and human disturbance.

Nanotechnologies for control of pathogenic microbial biofilms.

Biofilms are formed at interfaces by microorganisms, which congregate in microstructured communities embedded in a self-produced extracellular polymeric substance (EPS). Biofilm-related infections are problematic due to the high resistance towards most clinically used antimicrobials, which is associated with high mortality and morbidity, combined with increased hospital stays and overall treatment costs. Several new nanotechnology-based approaches have recently been proposed for targeting resistant bacteria and microbial biofilms. Here we discuss the impacts of biofilms on healthcare, food processing and packaging, and water filtration and distribution systems, and summarize the emerging nanotechnological strategies that are being developed for biofilm prevention, control and eradication. Combination of novel nanomaterials with conventional antimicrobial therapies has shown great potential in producing more effective platforms for controlling biofilms. Recent developments include antimicrobial nanocarriers with enzyme surface functionality that allow passive infection site targeting, degradation of the EPS and delivery of high concentrations of antimicrobials to the residing cells. Several stimuli-responsive antimicrobial formulation strategies have taken advantage of the biofilm microenvironment to enhance interaction and passive delivery into the biofilm sites. Nanoparticles of ultralow size have also been recently employed in formulations to improve the EPS penetration, enhance the carrier efficiency, and improve the cell wall permeability to antimicrobials. We also discuss antimicrobial metal and metal oxide nanoparticle formulations which provide additional mechanical factors through externally induced actuation and generate reactive oxygen species (ROS) within the biofilms. The review helps to bridge microbiology with materials science and nanotechnology, enabling a more comprehensive interdisciplinary approach towards the development of novel antimicrobial treatments and biofilm control strategies.

Species-specific plant-mediated effects between herbivores converge at high damage intensity.

Plants are often exposed to multiple herbivores and densities of these attackers (or corresponding damage intensities) often fluctuate greatly in the field. Plant-mediated interactions vary among herbivore species and with changing feeding intensity, but little is known about how herbivore identity and density interact to determine plant responses and herbivore fitness. Here, we investigated this question using Triadica sebifera (tallow) and two common and abundant specialist insect herbivores, Bikasha collaris (flea beetle) and Heterapoderopsis bicallosicollis (weevil). By manipulating densities of leaf-feeding adults of these two herbivore species, we tested how variations in the intensity of leaf damage caused by flea beetle or weevil adults affected the performance of root-feeding flea beetle larvae and evaluated the potential of induced tallow root traits to predict flea beetle larval performance. We found that weevil adults consistently decreased the survival of flea beetle larvae with increasing leaf damage intensities. In contrast, conspecific flea beetle adults increased their larval survival at low damage then decreased larval survival at high damage, resulting in a unimodal pattern. Chemical analyses showed that increasing leaf damage from weevil adults linearly decreased root carbohydrates and increased root tannin, whereas flea beetle adults had opposite effects as weevil adults at low damage and similar effects as them at high damage. Furthermore, across all feeding treatments, flea beetle larval survival correlated positively with concentrations of carbohydrates and negatively with concentration of tannin, suggesting that root primary and secondary metabolism might underlie the observed effects on flea beetle larvae. Our study demonstrates that herbivore identity and density interact to determine systemic plant responses and plant-mediated effects on herbivores. In particular, effects are species-specific at low densities, but converge at high densities. These findings emphasize the importance of considering herbivore identity and density simultaneously when investigating factors driving plant-mediated interactions between herbivores, which advances our understanding of the structure and composition of herbivore communities and terrestrial food webs.

Antibacterial secondary metabolites from Vernonia auriculifera Hiern (Asteraceae) against MDR phenotypes.

Purification of the aerial parts of Vernonia auriculifera Hiern afforded steroids (1-2), flavonoids (3-5), and polyalcohol (6). Their structures were determined using spectral evidences as well as by comparison with reported data. Iodonitrotetrazolium chloride (INT) colorimetric assay was used to assess the antibacterial activity of the extract and isolates against 13 pathogenic strains. The crude extract showed strong antibacterial activity (MIC < 100 µg/mL) against the tested bacterial strains. When combined with an efflux pump inhibitor phenylalanine beta naphthylamide (PAßN), the inhibition potency of the extract was substantially enhanced with the lowest MIC value at 4 µg/mL. Compounds 5 and 6 showed moderate activity (MIC < 100 µg/mL) against 12/13 (92.3%), and 8/13 (61.5%) bacterial strains, respectively. A minimal bactericidal concentration (MBC)/minimal inhibitory concentration (MIC) ratio ≤ 4 indicated their bactericidal effect against Escherichia coli, Enterbacter aerogenes, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosa, and Staphylococcus aureus.

Experiences and Motivations of Male Nurses in a Tertiary Hospital in Ghana.

INTRODUCTION: Nurses make up the largest portion of the health care system throughout the world, hence, making the profession the backbone of health care. The nursing workforce is made up of both males and females. However, the majority of nurses are predominately females with the number of male nurses reported to be unappreciable. OBJECTIVE: The study therefore aimed to explore the experiences and motivation of male nurses in a tertiary hospital in Ghana. METHODS: A qualitative descriptive research design was employed to explore the lived experiences of male nurses. A total of 20 male nurses were purposively selected, and in-depth interviews were conducted with a semi-structured interview guide. The interviews were tape-recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: The findings revealed 2 major themes: motivation and experiences of male nurses. The subthemes were individual motivations, external influence, intersecting social reactions and public perceptions, mixed encounters with patients, and satisfaction with the profession. CONCLUSION: Male nurses are motivated to a large extent to be part of the nursing profession but will be deeply involved in the profession if some factors affecting them are addressed. Future studies may address the roles of nurse managers in mentoring more males to be involved in the nursing profession.

Diet-induced iron deficiency in rats impacts small intestinal calcium and phosphate absorption.

AIMS: Recent reports suggest that iron deficiency impacts both intestinal calcium and phosphate absorption, although the exact transport pathways and intestinal segment responsible have not been determined. Therefore, we aimed to systematically investigate the impact of iron deficiency on the cellular mechanisms of transcellular and paracellular calcium and phosphate transport in different regions of the rat small intestine. METHODS: Adult, male Sprague-Dawley rats were maintained on a control or iron-deficient diet for 2 weeks and changes in intestinal calcium and phosphate uptake were determined using the in situ intestinal loop technique. The circulating levels of the hormonal regulators of calcium and phosphate were determined by ELISA, while the expression of transcellular calcium and phosphate transporters, and intestinal claudins were determined using qPCR and western blotting. RESULTS: Diet-induced iron deficiency significantly increased calcium absorption in the duodenum but had no impact in the jejunum and ileum. In contrast, phosphate absorption was significantly inhibited in the duodenum and to a lesser extent the jejunum, but remained unchanged in the ileum. The changes in duodenal calcium and phosphate absorption in the iron-deficient animals were associated with increased claudin 2 and 3 mRNA and protein levels, while levels of parathyroid hormone, fibroblast growth factor-23 and 1,25-dihydroxy vitamin D3 were unchanged. CONCLUSION: We propose that iron deficiency alters calcium and phosphate transport in the duodenum. This occurs via changes to the paracellular pathway, whereby upregulation of claudin 2 increases calcium absorption and upregulation of claudin 3 inhibits phosphate absorption.

Spontaneous regression of ALK fusion protein-positive non-small cell lung carcinoma: a case report and review of the literature.

BACKGROUND: ALK-rearrangement is observed in < 5% non-small cell lung cancer (NSCLC) cases and prior to the advent of oral tyrosine kinase inhibitors, the natural history of oncogenic NSCLC was typically poor. Literature relating to regression of treatment-naïve NSCLC is limited, and regression without treatment has not been noted in the ALK-rearranged sub-population. CASE PRESENTATION: A 76 year old 'never smoker' female with an ALK-rearranged left upper lobe T2 N0 NSCLC experienced a stroke following elective DC cardioversion for new atrial fibrillation. Following a good recovery, updated imaging demonstrated complete regression of the left upper lobe lesion and a reduction of the previously documented mediastinal lymph node. Remaining atelectasis was non-avid on repeat PET-CT imaging, 8 months from the baseline PET-CT. When the patient developed new symptoms 6 months later a further PET-CT demonstrated FDG-avid local recurrence. She completed 55 Gy in 20 fractions but at 18 months post-radiotherapy there was radiological progression in the lungs with new pulmonary metastases and effusion and new bone metastases. Owing to poor performance status, she was not considered fit for targeted therapy and died 5 months later. CONCLUSION: All reported cases of spontaneous regression in lung cancer have been collated within. Documented precipitants of spontaneous regression across tumour types include biopsy and immune reconstitution; stroke has not been reported previously. The favourable response achieved with radical radiotherapy alone in this unusual case of indolent oncogenic NSCLC reinforces the applicability of radiotherapy in locally advanced ALK-rearranged tumours, in cases not behaving aggressively. As a common embolic event affecting the neurological and pulmonary vasculature is less likely, an immune-mediated mechanism may underpin the phenomenon described in this patient, implying that hitherto unharnessed principles of immuno-oncology may have relevance in oncogenic NSCLC. Alternatively, high electrical voltage applied percutaneously adjacent to the tumour during cardioversion in this patient may have induced local tumour cell lethality.

Aluminum tolerance mechanisms in Kenyan maize germplasm are independent from the citrate transporter ZmMATE1.

Aluminum (Al) toxicity on acid soils adversely affects maize yields, which can be overcome by combining soil amendments with genetic tolerance. In maize, ZmMATE1 confers Al tolerance via Al-activated citrate release, whereby citrate forms non-toxic complexes with Al3+ in the rhizosphere. Here, we investigated Al tolerance mechanisms in maize germplasm originated from Kenya based on quantitative trait loci (QTL) mapping. Five QTLs and four epistatic interactions explained ~51% of the phenotypic variation for Al tolerance. The lack of Al tolerance QTL on chromosome 6 and the much lower expression of ZmMATE1 in both Kenyan lines than in Cateto Al237, which donates the superior allele of ZmMATE1, strongly indicate that this gene does not play a significant role in Al tolerance in neither parent. In turn, maize homologs to genes previously implicated in Al tolerance in other species, ZmNrat1, ZmMATE3, ZmWRKY and ZmART1, co-localized with Al tolerance QTL and were more highly expressed in the parent that donate favorable QTL alleles. However, these candidate genes will require further studies for functional validation on maize Al tolerance. The existence of Al tolerance mechanisms independent from ZmMATE1 suggests it is possible to develop highly Al tolerant cultivars by pyramiding complementary Al tolerance genes in maize.

Lived experiences of caregivers of children with autism spectrum disorder in Kenya.

BACKGROUND: Autism spectrum disorder (ASD) is a global public health concern. In African countries such as Kenya, there is a greater need for establishing support services for developmental disorders such as ASD. The emotional, social and economic burden of ASD on caregivers is unknown because of a number of challenges. Citizens of Kenya have a unique view of disability and inclusion. OBJECTIVES: To explore the perspectives of caregivers who are responsible for caring for both family and children living with ASD and to highlight the needs of children with ASD as well as the needs of their caregivers. METHOD: A qualitative, descriptive phenomenological study utilising focus group discussions (FGDs) was conducted. Verbatim transcription was used. QSR N 'Vivo 10 was used to organise and analyse the data. Content analysis was used to identify important ideas and concepts. RESULTS: One theme, namely 'the burden of caring for children with ASD', was identified. Children with ASD and their caregivers experience isolation and stigmatisation. CONCLUSION: Occupational therapists in Kenya should collaborate with the relevant national and global stakeholders for the promotion of the inclusion of children with ASD and their families. Responsive and context-appropriate occupational therapy interventions may begin to address service barriers. KEYWORDS: autism spectrum disorder; children; needs of caregivers; context-appropriate services.

A Modified ToxT Inhibitor Reduces Vibrio cholerae Virulence in Vivo.

We have previously designed and synthesized small-molecule inhibitors that reduce Vibrio cholerae virulence in vitro by targeting the transcription factor ToxT. Here we report the synthesis and biological activity of derivatives of our previous bicyclic, fatty acid-like inhibitors. All of the synthesized derivatives show antivirulence activity in vitro. For the most potent compounds, a concentration of 5 µM completely inhibited ToxT-mediated tcpA expression as measured in the ß-galactosidase assay. One indole compound, 3-(1-butyl-1 H-indol-7-yl)propanoic acid (8), was also effective at inhibiting intestinal colonization in the infant mouse. These modified compounds may serve as good candidates for further anti-cholera drug development.

Lateral condylar fractures of the humerus in children: does the type of fixation matter?

Aims: Displaced fractures of the lateral condyle of the humerus are frequently managed surgically with the aim of avoiding nonunion, malunion, disturbances of growth and later arthritis. The ideal method of fixation is however not known, and treatment varies between surgeons and hospitals. The aim of this study was to compare the outcome of two well-established forms of surgical treatment, Kirschner wire (K-wire) and screw fixation. Patients and Methods: A retrospective cohort study of children who underwent surgical treatment for a fracture of the lateral condyle of the humerus between January 2005 and December 2014 at two centres was undertaken. Pre, intraoperative and postoperative characteristics were evaluated. A total of 336 children were included in the study. Their mean age at the time of injury was 5.8 years (0 to 15) with a male:female patient ratio of 3:2. A total of 243 (72%) had a Milch II fracture and the fracture was displaced by > 2 mm in 228 (68%). In all, 235 patients underwent K-wire fixation and 101 had screw fixation. Results: There was a higher rate of nonunion with K-wire fixation (p = 0.02). There was no difference in Baumann's angle, carrying angle or the rate of major complications between the two groups. No benefit was obtained by immobilizing the elbow for more than four weeks in either group. No short-term complications were seen when fixation crossed the lateral ossific nucleus. Conclusion: Fixation of lateral condylar humeral fractures in children using either K-wires or screws gives satisfactory results. Proponents of both techniques may find justification of their methods in our data, but prospective, randomized trials with long-term follow-up are required to confirm the findings, which suggest a higher rate of nonunion with K-wire fixation. Cite this article: Bone Joint J 2018;100-B:387-95.

Design, synthesis, and biological activity of second-generation synthetic oleanane triterpenoids.

We report the synthesis and biological activity of C-24 demethyl CDDO-Me 2 and the C-28 amide derivatives 3 and 4, which are analogues of the anti-inflammatory synthetic triterpenoid bardoxolone methyl (CDDO-Me) 1. Demethylation of the C-24 methyl group was accomplished via "abnormal Beckmann" rearrangement and subsequent ring A reformation. Amides 3 and 4 were found to be potent inhibitors of the production of the inflammatory mediator NO in vitro.

A new class of inhibitors of the AraC family virulence regulator Vibrio cholerae ToxT.

Vibrio cholerae is responsible for the diarrheal disease cholera that infects millions of people worldwide. While vaccines protecting against cholera exist, and oral rehydration therapy is an effective treatment method, the disease will remain a global health threat until long-term solutions such as improved sanitation and access to clean water become widely available. Because of this, there is a pressing need for potent therapeutics that can either mitigate cholera symptoms, or act prophylactically to prevent the virulent effects of a cholera infection. Here we report the design, synthesis, and characterization of a set of compounds that bind and inhibit ToxT, the transcription factor that directly regulates the two primary V. cholerae virulence factors. Using the folded structure of the monounsaturated fatty acid observed in the X-ray structure of ToxT as a template, we designed ten novel compounds that inhibit the virulence cascade to a greater degree than any known inhibitor. Our findings provide a structural and functional basis for the development of viable antivirulence therapeutics that combat cholera and, potentially, other forms of bacterial pathogenic disease.

Synthesis of a Masked 2,3-Diaminoindole.

A three-step synthesis of masked 2,3-diaminoindole 1 from 2-iodo-3-nitro-1-(phenylsulfonyl)indole (2) has been developed. Treatment of 1 with trifluoroacetic acid generates the unstable 2,3-diamino-1-(phenylsulfonyl)indole (3), which can be trapped with α-dicarbonyl compounds to afford 5H-pyrazino[2,3-b]indoles 7-10.

In situ diagnostic methods for catheter related bloodstream infection in burns patients: A pilot study.

BACKGROUND: One of the most common and potentially fatal complications in critically ill burns patients is catheter related bloodstream infection (CR-BSI). Lack of in situ diagnostic techniques requires device removal if CR-BSI is suspected with 75-85% of catheters withdrawn unnecessarily. AIMS: To assess the sensitivity, specificity and accuracy of two in situ diagnostic methods for CR-BSI in an adult ICU burns population: Differential Time to Positivity (DTP) and Semi-Quantitative Superficial Cultures (SQSC). METHODS: Both arterial (AC) and central venous (CVC) catheters were studied. On clinicians' suspicion of CR-BSI, the CVC and AC were removed. Superficial semi-quantitative cultures were taken by removing the dressings and swabbing within a 3cm radius of the CVC and AC insertion sites, as well as inside each hub of the CVC and AC. Peripheral blood was taken for qualitative culture and the catheter tip sent for semi-quantitative culture. DTP was considered positive if culture of lumen blood became positive at least 120min before peripheral blood with an identical pathogen. Superficial and tip cultures were identified as positive if ≥15 CFUs were grown. CR-BSI was confirmed when both catheter tip culture and peripheral blood culture were positive with the same micro-organism. RESULTS: Sixteen patients (88% male) with an APACHE II score of 22.0 (7.3) were enrolled. The mean age was 45.7 (16.9) years with mean total burn surface area 32.9 (19.4)%. Fifty percent had airway burns. ICU stay was 19.9 (11.1) days. All 16 survived ICU discharge with a hospital survival of 93%. There were 20 episodes of CR-BSI in these 16 patients. For these 20 episodes the exposure time (line days) was 113.15. The CR-BSI rate was 15.6 per 1000 catheter days (95% CI 1.9-56.4). For diagnosis of CR-BSI in either AC and CVC, SQSC had a sensitivity of 50% [95% CI 3-97], specificity 83.3% [95% CI 67-93], PPV 14.3 [95% CI 1-58], NPV 96.8 [95% CI 81-100], accuracy of 81.6% [95%CI 65-92] and diagnostic odds ratio 5.0 [95% CI 0.3-91.5]. To diagnose tip colonisation (>15CFU), sensitivity of SQSC was 75% [95% CI 22-99], specificity 88.2% [95%CI 72-96], PPV 42.7 [95% CI 12-80], NPV96.8% [95% CI 81-100], accuracy 86.8% [95% CI 71-95] and diagnostic odds ratio 22.5 [95% CI 1.9-271.9]. For combined DTP blood cultures, sensitivity for CR-BSI was 50% [95% CI 3-97], with specificity 97% [95% CI 82-100], PPV 50% [5% CI 3-97%], NPV 97% [95% CI 82-100], accuracy 94.3% 95% CI 79-99] and diagnostic odds ratio 32 [95% CI 1.1-970.8]. CONCLUSION: Both DTP and SQSC displayed high specificity, NPV and accuracy in a population of adult burns patients. These features may make these tests useful for ruling out CR-BSI in this patient group. This study was limited by a low number of events and further research is required.

Triple Benzannulation of Naphthalene via a 1,3,6-Naphthotriyne Synthetic Equivalent. Synthesis of Dibenz[a,c]anthracene.

A new synthesis of dibenzo[a,c]anthracene (4) is described that features the generation, from tetrabromo-bis-triflate 1 and phenyllithium, of a 1,3,6-naphthotriyne (2) synthetic equivalent that is trapped with 3 equiv of furan to form Diels-Alder tris-adduct 3. A subsequent two-step deoxygenation of 3 represents the first synthesis of dibenz[a,c]anthracene (4) that involves a tandem aryne Diels-Alder cycloaddition-deoxygenation strategy.