Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study.

BACKGROUND: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I-V). METHODS: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. FINDINGS: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000-236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. INTERPRETATION: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. FUNDING: Duke-NUS Academic Medical Center Nurturing Clinician Researcher Scheme, and the Genedant-GIS Innovation Program.

Universal screening for Lynch syndrome in endometrial cancer diagnoses in Auckland, New Zealand: The initial experience.

BACKGROUND: Universal mismatch repair immunohistochemistry (MMR IHC) tumour testing in endometrial cancer (EC) for Lynch syndrome (LS) was introduced in Auckland, New Zealand, in January 2017. Identifying patients with LS allows them and their families to access risk reduction strategies. Universal MMR IHC testing aids in the molecular classification of EC and has prognostic and therapeutic implications. AIM: We aimed to determine the incidence of LS in women with EC in Auckland, New Zealand, following the introduction of MMR testing and the impact of universal screening on local genetic services. MATERIALS AND METHODS: This is a retrospective clinicopathological evaluation of women with a new EC diagnosis referred to the Auckland Gynaecological Oncology Unit from 1/1/17 to 31/12/18. Patient data were extracted from the Gynaecological Oncology Unit database and electronic records, and analysed using descriptive statistics. RESULTS: During the study period, 409 patients were diagnosed with EC, with an over-representation of Pacific Islanders (32.5%). Of these, 82.6% underwent MMR IHC testing, 20% were MMR-deficient (MMRd), and 71% had somatic hypermethylation. The Pacific Islander population had a 64% (odds ratio 0.36, P = 0.005) reduction in the odds of having MMRd tumours compared with Europeans. Of the patients who underwent MMR IHC testing, 5.5% were referred to a genetic clinic for germline testing. LS was confirmed in eight patients (2.3%). CONCLUSION: LS was diagnosed in 2.3% of patients. There was an over-representation of Pacific Islanders in the EC group but not among those diagnosed with LS.

Effect of CdS loading on the properties and photocatalytic activity of MoS2 nanosheets.

Molybdenum sulfide (MoS2) and modified MoS2 with different percentages of CdS (10%, 30%, and 50% CdS@MoS2) were successfully synthesized and characterized. The photocatalytic performance of the MoS2 and CdS@MoS2 was evaluated by degrading brilliant green (BG), methylene blue (MB), and rhodamine B (RhB) dyes under visible light irradiation. Amongst the synthesized photocatalysts, 50% CdS@MoS2 exhibited the highest photocatalytic activity, degrading 97.6%, 90.3%, and 75.5% of BG, MB, and RhB dyes, respectively within 5 h. The active species involved in the degradation processes were investigated. All trapping agents inhibited BG and MB degradation to a similar extent, indicating that all of the probed active species play an important role in the degradation of BG and MB. In contrast, h+ and O2•- were found to be the main reactive species in the photocatalytic RhB degradation. A potential mechanism for the photocatalytic degradation of dyes using CdS@MoS2 has been proposed. This work highlights the potential of CdS@MoS2 as a photocatalyst for more efficient water remediation applications.

The third PLeuralEffusion And Symptom Evaluation (PLEASE-3) study: Bendopnoea in patients with pleural effusion.

Background: Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a 'trial and error' basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE-3 study will evaluate bendopnoea as a screening test for effusion-related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism. Methods: PLEASE-3 is a multi-centre prospective study. Eligible patients are assessed at baseline (pre-drainage) and for patients undergoing drainage, up to 72 h post-procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants. Discussion: This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes. Trial Registration: Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12622000465752. URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Date of registration: Registered on 24 March 2022. Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not-for-profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ bi.lam@resphealth.uwa.edu.au Role of sponsor : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.

Management of malignant pleural effusion and trapped lung: a survey of respiratory physicians and thoracic surgeons in Australasia.

BACKGROUND: Malignant pleural effusions (MPEs) are common, and a third of them have underlying trapped lung (TL). Management of MPE and TL is suspected to be heterogeneous. Understanding current practices in Australasia is important in guiding policies and future research. AIMS: Electronic survey of Australia-New Zealand respiratory physicians, thoracic surgeons and their respective trainees to determine practice of MPE and TL management. RESULTS: Of the 132 respondents, 56% were respiratory physicians, 23% were surgeons and 20% were trainees. Many respondents defined TL as >25% or any level of incomplete lung expansion; 75% would use large-volume thoracentesis to determine whether TL was present. For patients with TL, indwelling pleural catheters (IPCs) were the preferred treatment irrespective of prognosis. In those without TL, surgical pleurodesis was the most common choice if prognosis was >6 months, whereas IPC was the preferred option if survival was <3 months. Only 5% of respondents considered decortication having a definite role in TL, but 55% would consider it in select cases. Forty-nine per cent of surgeons would not perform decortication when the lung does not fully expand intra-operatively. Perceived advantages of IPCs were minimisation of hospital time, effusion re-intervention and usefulness irrespective of TL status. Perceived disadvantages of IPCs were lack of suitable drainage care, potentially indefinite duration of catheter-in-situ and catheter complications. CONCLUSION: This survey highlights the lack of definition of TL and heterogeneity of MPE management in Australasia, especially for patients with expandable lungs. This survey also identified the main hurdles of IPC use that should be targeted.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

A questionnaire study on disparity of cervical cancer prevention programs in Asia-Oceania.

BACKGROUND: Despite the introduction of cervical cancer screening and human papillomavirus (HPV) vaccines, the utilization pattern was not standardized. The aim of this study was to elicit the current prevention care in Asia-Oceania. METHODS: An online questionnaire was circulated to different countries/cities in Asia-Oceania. The primary objective was to evaluate the coverage of HPV vaccination and cervical screening programs. The secondary objectives were to study the structures of these programs. Five case scenarios were set to understand how the respondents manage the abnormal screening results. RESULTS: Fourteen respondents from 10 countries/cities had participated. Cervical cancer ranked the first in Myanmar and Nepal. About 10%-15% did not have national vaccination or screening program. The estimated coverage rate for vaccination and screening varied from less than 1% to 70%, which the coverage ran in parallel with the incidence and mortality rates of cervical cancer. All regions approved HPV vaccines, although only four provided free or subsidized programs for nonavalent vaccine. Cervical cytology remained the most common screening tool, and 20%-30% relied heavily on visual inspection using acetic acid. The screening age groups varied in different regions. From the case scenarios, it was noted that some respondents tended to offer more frequent screening tests or colposcopy than recommended by international guidelines. CONCLUSION: This study revealed discrepancy in the practice of cervical cancer prevention in Asia-Oceania especially access to HPV vaccines. There is an urgent need for a global collaboration to eliminate cervical cancer by public education, reforming services, and medical training.

Relapsing Aspergillus otomycosis despite prolonged systemic antifungal therapy and resolution after topical voriconazole administration: A case report.

We report a case of intractable Aspergillus otomycosis with multiple relapses despite conventional topical and systemic antifungal treatment, and adjunctive usage of hyperbaric oxygen therapy. Of note, otomycosis relapsed even after six months of continuous systemic antifungal treatment with therapeutic drug levels and without treatment interruption; and only resolved after application of topical voriconazole. (max. 75 words).

Molybdenum Disulfide-Based Nanomaterials for Visible-Light-Induced Photocatalysis.

Visible-light-responsive photocatalytic materials have a multitude of important applications, ranging from energy conversion and storage to industrial waste treatment. Molybdenum disulfide (MoS2) and its variants exhibit high photocatalytic activity under irradiation by visible light as well as good stability and recyclability, which are desirable for all photocatalytic applications. MoS2-based materials have been widely applied in various fields such as wastewater treatment, environmental remediation, and organic transformation reactions because of their excellent physicochemical properties. The present review focuses on the fundamental properties of MoS2, recent developments and remaining challenges, and key strategies for tackling issues related to the utilization of MoS2 in photocatalysis. The application of MoS2-based materials in visible-light-induced catalytic reactions for the treatment of diverse kinds of pollutants including industrial, environmental, pharmaceutical, and agricultural waste are also critically discussed. The review concludes by highlighting the prospects of MoS2 for use in various established and emerging areas of photocatalysis.

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion.

INTRODUCTION: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. METHODS AND ANALYSIS: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. DISCUSSION: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. PROTOCOL VERSION: Version 3.00/4.02.19.

Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): A Pilot Randomized Clinical Trial.

Rationale: Pleural effusion commonly complicates community-acquired pneumonia and is associated with intense pleural inflammation. Whether antiinflammatory treatment with corticosteroids improves outcomes is unknown. Objectives: To assess the effects of corticosteroids in an adult population with pneumonia-related pleural effusion. Methods: The STOPPE (Steroid Therapy and Outcome of Parapneumonic Pleural Effusions) trial was a pilot, multicenter, double-blinded, placebo-controlled, randomized trial involving six Australian centers. Patients with community-acquired pneumonia and pleural effusion were randomized (2:1) to intravenous dexamethasone (4 mg twice daily for 48 h) or placebo and followed for 30 days. Given the diverse effects of corticosteroids, a comprehensive range of clinical, serological, and imaging outcomes were assessed in this pilot trial (ACTRN12618000947202). Measurements and Main Results: Eighty patients were randomized (one withdrawn before treatment) and received dexamethasone (n = 51) or placebo (n = 28). This pilot trial found no preliminary evidence of benefits of dexamethasone in improving time to sustained (>12 h) normalization of vital signs (temperature, oxygen saturations, blood pressure, heart, and respiratory rates): median, 41.0 (95% confidence interval, 32.3-54.5) versus 27.8 (15.4-49.5) hours in the placebo arm (hazard ratio, 0.729 [95% confidence interval, 0.453-1.173]; P = 0.193). Similarly, no differences in C-reactive protein or leukocyte counts were observed, except for a higher leukocyte count in the dexamethasone group at Day 3. Pleural drainage procedures were performed in 49.0% of dexamethasone-treated and 42.9% of placebo-treated patients (P = 0.60). Radiographic pleural opacification decreased over time with no consistent intergroup differences. Mean duration of antibiotic therapy (22.4 [SD, 15.4] vs. 20.4 [SD, 13.8] d) and median hospitalization (6.0 [interquartile range, 5.0-10.0] vs. 5.5 [interquartile range, 5.0-8.0] d) were similar between the dexamethasone and placebo groups. Serious adverse events occurred in 25.5% of dexamethasone-treated and 21.4% of placebo-treated patients. Transient hyperglycemia more commonly affected the dexamethasone group (15.6% vs. 7.1%). Conclusions: Systemic corticosteroids showed no preliminary benefits in adults with parapneumonic effusions. Clinical trial registered with www.anzctr.org.au (ACTRN12618000947202).

Effect of Zr doping on photoantioxidant and antibiofilm properties of CeO2 NPs fabricated using aqueous leaf extract of Pometia pinnata.

Synthesized cerium oxide nanoparticles (S-CeO2 NPs) and 1%, 5% and 10% zirconium doped CeO2 (Zr-doped CeO2) NPs were fabricated using aqueous leaf extract of Pometia pinnata. The synthesized NPs were characterized using standard techniques which confirmed successful synthesis of NPs with particle size ranging from 12 to 23 nm and band gap energy of 2.54-2.66 eV. Photoantioxidant activities showed enhanced activities under visible light irradiation in comparison to the dark condition in the dose-dependent study. Biofilm inhibition studies showed ~ 73% biofilm inhibition of Staphylococcus aureus at 512 µg/mL for S-CeO2, whereas 10% Zr-doped CeO2 NPs showed biofilm inhibition of 52.7%. The bactericidal tests showed killing properties at 1024 µg/mL of S-CeO2 NPs and at 512 µg/mL of 1% Zr-doped CeO2. Reduced bactericidal activities were observed for 5% and 10% Zr-doped CeO2. These studies showed that the fabricated NPs have both good photoantioxidant and antibacterial properties.

Candida Endophthalmitis Treated Successfully With Isavuconazole: A Case Report.

Candida endophthalmitis is a serious complication of candidemia. Diagnosis requires identification of ocular lesions on dilated fundoscopy, aided by isolation of the organism from blood and/or vitreous humor. However, the initial ophthalmological examination may be negative in some cases. Experience with isavuconazole for the treatment of Candida endophthalmitis is limited. We present a case of a 65-year-old woman with metastatic breast cancer on chemotherapy who developed Candida dubliniensis endophthalmitis with initial negative ophthalmological examination. She was treated with vitrectomy and 6 weeks of oral fluconazole. Despite vitrectomy and culture-directed antifungal treatment, management was complicated by lack of response to fluconazole and intolerance to other antifungals, necessitating the use of isavuconazole, which proved efficacious.

Green-synthesized CeO2 nanoparticles for photocatalytic, antimicrobial, antioxidant and cytotoxicity activities.

Cerium oxide nanoparticles (CeO2 NPs) are a sought-after material in numerous fields due to their potential applications such as in catalysis, cancer therapy, photocatalytic degradation of pollutants, sensors, polishing agents. Green synthesis usually involves the production of CeO2 assisted by organic extracts obtained from plants, leaves, flowers, bacteria, algae, food, fruits, etc. The phytochemicals present in the organic extracts adhere to the NPs and act as reducing and/or oxidizing agents and capping agents to stabilize the NPs, modify the particle size, morphology and band gap energy of the as-synthesized materials, which would be advantageous for numerous applications. This review focuses on the green extract-mediated synthesis of CeO2 NPs and discusses the effects on CeO2 NPs of various synthesis methods that have been reported. Several photocatalytic, antimicrobial, antioxidant and cytotoxicity applications have been evaluated, compared and discussed. Future prospects are also suggested.

Green synthesis of CeO2 and Zr/Sn-dual doped CeO2 nanoparticles with photoantioxidant and antibiofilm activities.

Cerium oxide (CeO2) and 1%, 5% and 10% zirconium/tin-dual doped CeO2 nanoparticles (Zr/Sn-dual doped CeO2 NPs) were synthesized using an aqueous leaf extract of Pometia pinnata. By using UV-visible diffuse reflectance spectroscopy, the band gap energies of these materials were found to be in the range of ∼2.49 to 2.66 eV. The average crystallite sizes of the fluorite phase obtained from X-ray diffraction were between 7 and 16 nm. X-ray photoelectron spectroscopy (XPS) analysis further confirmed the synthesis of CeO2 and Sn-doped CeO2 NPs. Almost spherical shapes of the nanomaterials with an average particle size of 12-17 nm were determined using scanning electron microscopy and transmission electron microscopy studies. Photoantioxidant activities of the synthesized materials showed enhanced photoantioxidant response under visible light irradiation in comparison with those under dark conditions in both dose- and time-dependent manner. The CeO2 NPs exhibited a significant concentration-dependent antibiofilm activity against the Gram-positive bacteria Staphylococcus aureus (S. aureus) and Listeria monocytogenes (L. monocytogenes). Only the 10% Zr/Sn-dual doped-CeO2 NPs were found to inhibit S. aureus biofilm formation at higher concentrations. All Zr/Sn-dual doped CeO2 NPs exhibited a concentration-dependent biofilm inhibition of L. monocytogenes and also bactericidal activity towards S. aureus. These nanomaterials exhibited enhanced photoantioxidant activities and antibacterial properties, which make them suitable for various biological applications.

Negative cerebrospinal fluid ß-d-glucan levels as an indicator for treatment cessation ahead of biochemical resolution: A case report of Candida glabrata meningitis.

Candida infections of the central nervous system (CNS) are rare. We report a case of Candida glabrata meningitis successfully treated with combination antifungal therapy followed by step-down therapy with fluconazole. New-onset hypercalcaemia, an uncommon side effect of the prolonged fluconazole treatment, prompted early treatment cessation. A negative cerebrospinal fluid (CSF) ß-d-glucan supported the decision of treatment cessation despite incomplete resolution of CSF biochemical parameters. No disease relapse was encountered after 2 years post-treatment.