Clinical factors associated with illness perception, worry and mental health in sclerosing cholangitis: A single centre prospective study.

BACKGROUND: A reduced quality of life and symptoms of depression and anxiety are reported in patients with primary sclerosing cholangitis (PSC), however specific risk factors and the effect of sclerosing cholangitis (SC) with autoimmune features are not known. OBJECTIVE: To integrate mental wellbeing assessment into routine clinical care for patients with SC, and evaluate factors associated with measures relating to quality of life, illness perception and mental health. METHODS: A prospective study of adult non-transplant patients with SC attending the outpatient clinic over a 1 year period. Self-reported questionnaires were sent to patients electronically prior to clinic to assess worry, illness perception, depression and anxiety. Demographic and clinical information was collected. RESULTS: Questionnaires were completed in 52/130 (40 %) patients with SC who attended clinic. Worry related to quality of life, mental and physical health, and future health were common. There was no difference in overall worry or illness perception in patients treated with ursodeoxycholic acid; whilst patients with PSC had a higher illness perception (P = 0.04) than those with SC and autoimmune features. Both worry (P = 0.047) and illness perception (P = 0.01) were higher in patients with elevated alkaline phosphatase, whilst there was no difference in patients with and without cirrhosis. There were high screening test scores for both depression (21.1 %) and anxiety (9.6 %), with no association with patient factors. CONCLUSIONS: We integrated an electronic questionnaire for completion prior to clinic for patients with SC with good uptake. We identified a high prevalence of patient worries and symptoms of depression and anxiety, which may be more common in PSC with elevated alkaline phosphatase and without autoimmune features. We recommend the adoption of similar tools into routine clinical practice for patients with SC.

New Zealand National GDM Guidelines: an alternative view of some good practice points.

The New Zealand Gestational Diabetes Mellitus (GDM) Guidelines, commissioned by the Ministry of Health, contains many good points, but several recommendations are creating controversy. This opinion piece discusses an alternative approach to early pregnancy screening for diabetes. We suggest that it is reasonable to refer women with an HbA1c ≥41 mmol/mol (5.9%) for further management, rather than the recommended referral threshold of ≥50 mmol/mol (6.7%). We also suggest that, for subsequent screening for GDM at 24-28 weeks' gestation, a 75 g oral glucose tolerance test should be offered rather than a 50 g glucose challenge test.

A novel fluorescent sensor protein for detecting changes in airway surface liquid glucose concentration.

Both lung disease and elevation of blood glucose are associated with increased glucose concentration (from 0.4 to ~4.0 mM) in the airway surface liquid (ASL). This perturbation of ASL glucose makes the airway more susceptible to infection by respiratory pathogens. ASL is minute (~1 µl/cm(2)) and the measurement of glucose concentration in the small volume ASL is extremely difficult. Therefore, we sought to develop a fluorescent biosensor with sufficient sensitivity to determine glucose concentrations in ASL in situ. We coupled a range of environmentally sensitive fluorophores to mutated forms of a glucose/galactose-binding protein (GBP) including H152C and H152C/A213R and determined their equilibrium binding properties. Of these, GBP H152C/A213R-BADAN (Kd 0.86 ± 0.01 mM, Fmax/F0 3.6) was optimal for glucose sensing and in ASL increased fluorescence when basolateral glucose concentration was raised from 1 to 20 mM. Moreover, interpolation of the data showed that the glucose concentration in ASL was increased, with results similar to that using glucose oxidase analysis. The fluorescence of GBP H152C/A213R-BADAN in native ASL from human airway epithelial cultures in situ was significantly increased over time when basolateral glucose was increased from 5 to 20 mM. Overall our data indicate that this GBP is a useful tool to monitor glucose homoeostasis in the lung.

Salmonella paratyphi A-infected ovarian cyst in returning traveller--an unusual complication of enteric fever.

We report a case of Salmonella paratyphi A enteric fever in a returned New Zealand traveller complicated by an infected ovarian cyst, which resulted in clinical and microbiological relapse despite appropriate antibiotic treatment. Extraintestinal manifestations of enteric fever are infrequent but should be considered in situations where treatment response to first-line antibiotics for adequate duration is suboptimal.

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.