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Topical intranasal anesthesia impairs trigeminal function and airflow perception.

Impairment of airflow perception by the intranasal trigeminal system may explain chronic nasal obstruction (CNO),especially in cases where no major deformity or mucosal inflammation can explain reduced airflow. We aim to characterize the effect of topical intranasal anesthesia on intranasal trigeminal sensitivity and consequently the sensation of nasal obstruction. We performed a crossover study of 16 healthy subjects, randomised for either treatment (topical intranasal anesthesia with 10% Xylocaine) or placebo (saline solution). We used the Trigeminal Lateralization Task (TLT) with eucalyptol to assess trigeminal sensitivity. We measured nasal patency objectively with Peak Nasal Inspiratory Flow (PNIF), and subjectively with a Visual Analog Scale (VAS), the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q), and the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire. Topical intranasal anesthesia significantly reduced intranasal trigeminal sensitivity. Further, after topical intranasal anesthesia,reduced trigeminal sensitivity was associated with the subjectively reduced nasal patency, as highlighted by ENS6Q and NOSE scores. Topical intranasal anesthesia reduces intranasal trigeminal function resulting in subjectively reduced nasal patency. In future studies, the relation of reduced intranasal trigeminal function and subjective nasal obstruction needs to be addressed to open an avenue for potential interventions for an important portion of ENT patients.

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Increased antibiotic resistance of Pseudomonas aeruginosa isolates from chronic rhinosinusitis patients grown in anaerobic conditions.

In chronic rhinosinusitis (CRS), the congestion and blockage of the nose can cause anaerobic conditions within the sinus cavities which may promote the expression of virulence and antibiotic resistance genes in invading pathogens. Pseudomonas aeruginosa is a facultative anaerobic bacteria and causes severe recalcitrant CRS. In this study, we aimed to evaluate the antimicrobial resistance of P. aeruginosa isolates of CRS patients in planktonic and biofilm form grown in aerobic and anaerobic conditions. P. aeruginosa clinical isolates of CRS patients (n = 25) were grown in planktonic and biofilm form in aerobic and anaerobic conditions. Minimum inhibitory concentrations (MIC) of planktonic forms and minimum biofilm eradication concentrations (MBEC) were determined. Additionally, metabolic activity by fluorescein diacetate assay, biofilm biomass by crystal violet assay and eDNA concentration were assessed in both conditions. P. aeruginosa planktonic cells grown in anaerobic condition exhibited increased gentamicin resistance (p < .01), whereas P. aeruginosa biofilms grown in anaerobic condition displayed significantly increased MBEC values for gentamicin (p < .0001) and levofloxacin (p < .001). The metabolic activity of anaerobic biofilms was significantly higher compared with aerobic biofilms (p < .0001). However, the biofilm biomass of isolates grown in aerobic conditions was higher than anaerobic conditions (p < .5). P. aeruginosa isolates from CRS patients grown in anaerobic conditions showed significantly increased resistance to antibiotics with an increased metabolic activity but decreased biofilm biomass. NA.

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Open Access
The Evolution of Pituitary Surgery in an Australian Health Care Framework

Abstract Background The outcomes in pituitary surgery have dramatically changed over the past 130 years. Endoscopic endonasal transsphenoidal approaches are now an accepted method for operating on pituitary tumors, a skillset which takes time to develop. The Australian health care framework provides a unique mixture of public and private care for a geographically dispersed population. In this article, we aim to examine how outcomes for patients in South Australia changed as endoscopic pituitary surgery was adopted and how the Australian health care framework influenced the development of a skull base team. Methods The case notes of all patients undergoing pituitary surgery between 2006 and 2020 in South Australia. All patients treated by this author group were included. Results A total of 428 pituitary adenomas were surgically treated. Overall, 182 out of 249 patients (70%) had a complete resection with no recurrence at follow-up, and 49 patients (19%) had a residual that was observed and did not require treatment. Therefore, 89% of patients between the years 2006 and 2020 did not require any further treatment following their pituitary surgery. Upon examination of the 142 patients with functional adenomas, 112 (79%) patients had no recurrence in hormonal dysfunction following surgery, and the remaining 30 (21%) patients required further treatment. Conclusion We have demonstrated that acceptable outcomes can be achieved in a low-to-moderate volume setting across multiple hospitals when a coordinated effort is made to consolidate these cases within a small group of subspeciality-trained surgeons, as opposed to a more generalist approach.

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Neuronavigation in endoscopic skull base surgery and the accuracy of different MRI sequences

ObjectiveNeuronavigation is common technology used by skull base teams when performing endoscopic endonasal surgery. A common practice of MRI imagining is to obtain 3D isotopic gadolinium enhanced T1W magnetisation prepared rapid gradient echo (MPRAGE) sequences. These are prone to distortion when undertaken on 3 T magnets. The aim of this project is to compare the in vivo accuracy of MRI sequences between current and new high resolution 3D sequences. The goal is to determine if geometric distortion significantly affects neuronavigation accuracy. MethodsPatients were scanned with a 3D T1 MPRAGE sequence, 3D T1 SPACE sequence and a CT stereotactic localisation. Following general anaesthesia, patients were registered on the Stealth Station (Medtronic, USA) using a side mount emitter for Electromagnetic navigation. A variety of surgically relevant anatomical landmarks in the sagittal and coronal plane were selected with real and virtual data points measured. ResultsA total of 10 patients agreed be enrolled in the study with datapoints collected during surgery. The distance between real and virtual datapoints trended to be lower in SPACE sequences compared to MPRAGE. Paired t test did not demonstrate a significant difference. ConclusionWe have demonstrated that navigational accuracy is not significantly affected by the type of MRI sequence selected and that current corrective algorithms are sufficient. Navigational accuracy is affected by many factors, with registration error likely playing the most significant role. Further research involving real time imaging such as endoscopic ultrasound may hopefully address this potential error.

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Open Access
Hybracter: Enabling Scalable, Automated, Complete and Accurate Bacterial Genome Assemblies.

Improvements in the accuracy and availability of long-read sequencing mean that complete bacterial genomes are now routinely reconstructed using hybrid (i.e. short- and long-reads) assembly approaches. Complete genomes allow a deeper understanding of bacterial evolution and genomic variation beyond single nucleotide variants (SNVs). They are also crucial for identifying plasmids, which often carry medically significant antimicrobial resistance (AMR) genes. However, small plasmids are often missed or misassembled by long-read assembly algorithms. Here, we present Hybracter which allows for the fast, automatic, and scalable recovery of near-perfect complete bacterial genomes using a long-read first assembly approach. Hybracter can be run either as a hybrid assembler or as a long-read only assembler. We compared Hybracter to existing automated hybrid and long-read only assembly tools using a diverse panel of samples of varying levels of long-read accuracy with manually curated ground truth reference genomes. We demonstrate that Hybracter as a hybrid assembler is more accurate and faster than the existing gold standard automated hybrid assembler Unicycler. We also show that Hybracter with long-reads only is the most accurate long-read only assembler and is comparable to hybrid methods in accurately recovering small plasmids.

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Open Access
Effect of Octamer-Binding Transcription Factor 4 Overexpression on the Neural Induction of Human Dental Pulp Stem Cells

Stem cell-based therapy is a potential alternative strategy for brain repair, with neural stem cells (NSC) presenting as the most promising candidates. Obtaining sufficient quantities of NSC for clinical applications is challenging, therefore alternative cell types, such as neural crest-derived dental pulp stem cells (DPSC), may be considered. Human DPSC possess neurogenic potential, exerting positive effects in the damaged brain through paracrine effects. However, a method for conversion of DPSC into NSC has yet to be developed. Here, overexpression of octamer-binding transcription factor 4 (OCT4) in combination with neural inductive conditions was used to reprogram human DPSC along the neural lineage. The reprogrammed DPSC demonstrated a neuronal-like phenotype, with increased expression levels of neural markers, limited capacity for sphere formation, and enhanced neuronal but not glial differentiation. Transcriptomic analysis further highlighted the expression of genes associated with neural and neuronal functions. In vivo analysis using a developmental avian model showed that implanted DPSC survived in the developing central nervous system and respond to endogenous signals, displaying neuronal phenotypes. Therefore, OCT4 enhances the neural potential of DPSC, which exhibited characteristics aligning with neuronal progenitors. This method can be used to standardise DPSC neural induction and provide an alternative source of neural cell types.Graphical

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Open Access
Influence of Socioeconomic Status on the Association Between Pregnancy Complications and Premature Coronary Artery Disease: Linking Three Cohorts.

We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk. This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case-control study design. Cases (n = 721), that is, women aged <60 years from Coronary Angiogram Database of South Australia (CADOSA) were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain prior pregnancy outcomes and SES. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS), comprising women who were healthy or had health conditions unrelated to CAD, age matched to CADOSA (±5 years), and linked to SAPSC to determine prior pregnancy outcomes and SES. This project performed comparative analysis of SES using socioeconomic indexes for areas-index of relative socioeconomic advantage and disadvantage (SEIFA-IRSAD) scores across three databases. Findings revealed that SEIFA-IRSAD scores at the time of pregnancy (p-value = 0.005) and increase in SEIFA-IRSAD scores over time (p-value = 0.040) were significantly associated with PCAD. In addition, when models were adjusted for SEIFA-IRSAD scores at the time of pregnancy and age, risk factors including placenta-mediated pregnancy complications such as preterm birth (odds ratio [OR] = 4.77, 95% confidence interval [CI]: 1.74-13.03) and history of a miscarriage (OR = 2.14, 95% CI: 1.02-4.49), and cardiovascular disease (CVD) risk factors including smoking (OR = 8.60, 95% CI: 3.25-22.75) were significantly associated with PCAD. When the model was adjusted for change in SEIFA-IRSAD scores (from CADOSA/NWAHS to SAPSC) and age, pregnancy-mediated pregnancy complications including preterm birth (OR = 4.40, 95% CI: 1.61-12.05) and history of a miscarriage (OR = 2.09, 95% CI: 1.00-4.35), and CVD risk factor smoking (OR = 8.75, 95% CI: 3.32-23.07) were significantly associated with PCAD. SES at the time of pregnancy and change in SES were not associated with PCAD risk.

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Open Access
IMPAACT: IMproving the PArticipAtion of older people in policy decision-making on common health CondiTions – a study protocol

IntroductionRapid population ageing is a demographic trend being experienced and documented worldwide. While increased health screening and assessment may help mitigate the burden of illness in older people, issues such as misdiagnosis may affect access to interventions. This study aims to elicit the values and preferences of evidence-informed older people living in the community on early screening for common health conditions (cardiovascular disease, diabetes, dementia and frailty). The study will proceed in three Phases: (1) generating recommendations of older people through a series of Citizens’ Juries; (2) obtaining feedback from a diverse range of stakeholder groups on the jury findings; and (3) co-designing a set of Knowledge Translation resources to facilitate implementation into research, policy and practice. Conditions were chosen to reflect common health conditions characterised by increasing prevalence with age, but which have been underexamined through a Citizens’ Jury methodology.Methods and analysisThis study will be conducted in three Phases—(1) Citizens’ Juries, (2) Policy Roundtables and (3) Production of Knowledge Translation resources. First, older people aged 50+ (n=80), including those from traditionally hard-to-reach and diverse groups, will be purposively recruited to four Citizen Juries. Second, representatives from a range of key stakeholder groups, including consumers and carers, health and aged care policymakers, general practitioners, practice nurses, geriatricians, allied health practitioners, pharmaceutical companies, private health insurers and community and aged care providers (n=40) will be purposively recruited for two Policy Roundtables. Finally, two researchers and six purposively recruited consumers will co-design Knowledge Translation resources. Thematic analysis will be performed on documentation and transcripts.Ethics and disseminationEthical approval has been obtained through the Torrens University Human Research Ethics Committee. Participants will give written informed consent. Findings will be disseminated through development of a policy brief and lay summary, peer-reviewed publications, conference presentations and seminars.

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Open Access