A Novel Antifungal Is Active against Candida albicans Biofilms and Inhibits Mutagenic Acetaldehyde Production In Vitro

Peer reviewe

The role of noninvasive ventilation in the management of type II respiratory failure in patients with myotonic dystrophy

Type 1 myotonic dystrophy (DM1) causes sleep disordered breathing and respiratory failure due to a combination of obstructive sleep apnoea, reduced central drive and respiratory muscle weakness. Noninvasive ventilation (NIV) is commonly used for treating respiratory failure in neuromuscular disease; however, there have been few studies assessing the role of NIV in DM1. The aim of this retrospective service evaluation was to investigate the impact of NIV adherence on hypercapnia and symptoms of hypoventilation in patients with DM1. Data on capillary carbon dioxide tension (PCO2), lung function, adherence to NIV and symptoms of hypoventilation were obtained from the records of 40 patients with DM1. Mean capillary PCO2 significantly reduced from 6.81±1.17 kPa during supervised inpatient set-up to 5.93±0.82 kPa after NIV set-up (p<0.001). NIV adherence reduced from 7.8 (range: 1.0–11.0) h per 24 h during supervised inpatient set-up to 2.9 (0–10.4) h per 24 h in the community. Overall 72% of patients used NIV <5 h per 24 h during follow-up, including 11% who discontinued NIV completely. There was no correlation between adherence to NIV and changes in capillary PCO2. Patients who reported symptomatic benefit (50%) had higher adherence than those who did not feel benefit (p<0.05). In conclusion, in patients with myotonic dystrophy with Type II respiratory failure maintaining adherence is challenging

Can use of the serum anti-PLA2R antibody negate the need for a renal biopsy in primary membranous nephropathy?

Background Since the emergence of the anti-PLA2R antibody (PLA2R-Ab) test, nephrology practice has not changed dramatically, with most nephrologists still relying on a kidney biopsy to diagnose membranous nephropathy. In this study, we examined the clinical accuracy of the anti-PLA2R antibody test using ELISA in routine clinical care. Methods We conducted a retrospective analysis of PLA2R-Ab testing in 187 consecutive patients seen at a single UK centre between 2003 and 2020. We compared the kidney biopsy findings with the PLA2R-ab antibody test. Patients’ demography, urine protein creatinine ratios, serum albumin, and treatment characteristics including supportive and immunosuppressive treatment were recorded. The clinical accuracy of the test (e.g. sensitivity and specificity, positive [PPV] and negative [NPV] predictive values) was calculated using the kidney biopsy findings as the diagnostic reference. Results Mean levels of PLA2R-Ab titre in primary membranous nephropathy were 217RU/ml in comparison to 3RU/ml for both secondary membranous nephropathy and other diagnoses. Most patients with a positive PLA2R-Ab test had a confirmed renal biopsy diagnosis of primary membranous nephropathy with: PPV of 97.3%, sensitivity 75.5%, NPV was 79.8% and specificity was 97.8% at a cut-off threshold of >20 RU/ml. Conclusion The anti-PLA2R antibody test is a highly specific test for diagnosing membranous nephropathy, and the test has the potential to allow for the diagnosis and treatment in up to 75% of PMN cases without the need for a renal biopsy. Nevertheless, patients with negative PLA2R-Ab tests will still require a biopsy to confirm their diagnosis

Changes in metabolic activity and biomass of <i>C. albicans</i> biofilms.

<p>Metabolic activities measured by XTT-assay (panel A, B) and dsDNA levels (panel C, D) reflecting the biomass of <i>C. albicans</i> biofilms at pH 5.2 and 7.4. Biofilms were grown for 4, 24 or 48 h in RPMI at pH 7.4 and then exposed to PBS, caspofungin, HICA, leucine, cysteine or ethanol for another 24 h. Values were measured twice in triplicate and expressed as mean (±SEM). Means were compared to the control treatment (RPMI). Statistically significant differences were calculated using a GEE-model and were marked (**p<0.001,* 0.001</p

Summary of study design.

<p>Summary of study design.</p

ACH production by <i>C. albicans</i> biofilms.

<p>Mean (±SEM) ACH production by <i>C. albicans</i> biofilms. Biofilms at three different stages of growth (4 h, 24 h and 48 h), were incubated for 30 min at 37°C with 100 mM D-glucose (A,B) or 0.05% ethanol (C,D) after 24 h exposure to RPMI, ethanol, caspofungin or HICA at pH 5.2 or 7.4. Values were measured twice in triplicate and means were compared at each time point to the control treatment (RPMI). Statistically significant differences were calculated using a GEE-model and were marked (**p<0.001, * 0.001</p

Microscopic examination of <i>C. albicans</i> biofilms exposed to HICA.

<p>SEM images were taken of biofilms which were grown for 24% HICA for another 24 h at pH 5.2 (A) or pH 7.4 (B). Control images were taken of biofilms grown in RPMI-medium without HICA at pH 5.2 (C) or pH 7.4 (D). Insets show hyphal structures in detail. Scale bars indicate 10 µm in main images and 5 µm in insets.</p

Relative expression of genes related to ACH metabolism.

<p>(A) A schematic model of central carbon metabolism incorporated with genes of interest within ethanol metabolism (abbreviations as follows: G6P =  glucose-6-phosphate, KICA =  α-ketoisocaproic acid). (B) Heat map panel of gene expression in <i>C. albicans</i> biofilms at three different stages of growth at pH 5.2 and 7.4 after 24 h exposure to PBS, caspofungin, HICA, leucine, cysteine or ethanol. Fold changes are expressed relative to control (RPMI) at the corresponding time point. Black represents no change in expression, green is up-regulation, and red is down-regulation. A brighter color indicates greater degree of change in expression. Relative gene expressions were calculated by the Pfaffl method using the REST 2009 software provided by Qiagen <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097864#pone.0097864-Pfaffl1" target="_blank">[63]</a>.</p