Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

Retinal arteriolar geometry is associated with cerebral white matter hyperintensities on MRI

Background. Cerebral small vessel disease (lacunar stroke and cerebral white matter hyperintensities) is caused by vessel abnormalities of unknown aetiology. Retinal vessels show developmental and pathophysiological similarities to cerebral small vessels and microvessel geometry may influence vascular efficiency. Hypothesis. We hypothesized that retinal arteriolar branching angles or co-efficients (the ratio of the sum of the cross sectional areas of the two daughter vessels to the cross sectional area of the parent vessel at an arteriolar bifurcation) may be associated with cerebral small vessel disease. Methods. We performed a cross-sectional observational study in a tertiary referral hospital, United Kingdom. An experienced stroke physician recruited consecutive patients presenting with lacunar ischaemic stroke with a control group consisting of patients with minor cortical ischaemic stroke. We performed brain magnetic resonance imaging to assess the recent infarct and periventricular and deep white matter hyperintensities. We subtyped stroke with clinical and radiological findings. We took digital retinal photography to assess retinal arteriolar branching co-efficients and branching angles using a semi-automated technique. Results. We recruited 205 patients (104 lacunar stroke, 101 cortical stroke), mean age 68 (Standard Deviation 12) years. With multivariate analysis, increased branching coefficient was associated with periventricular white matter hyperintensities (p=0.006) and ischaemic heart disease (p<0.001); decreased branching co-efficient with deep white matter hyperintensities (p=0.003) but not with lacunar stroke subtype (p=0.96). We found no associations with retinal branching angles. Conclusions. Retinal arteriolar geometry differs between cerebral small vessel phenotypes. More research is needed to ascertain the clinical significance of these findings

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

The impact of a cerebellar tumour on language function in childhood

Background/Aims: Childhood-acquired cerebellar studies to date have appeared to present a concordant pattern of specific neuropsychological profiles depending on lesion site. The aim was to determine the impact of a cerebellar tumour specifically on language function in children by reporting both the general and high-level language abilities of 4 cases with differing sites of hemispheric and vermal involvement. Methods: The language abilities of 4 children ( aged from 7 years 9 months to 13 years), treated with surgery and/or radiotherapy for cerebellar tumour 6 months to 3 years previously, were examined. A standardized battery of general and high-level language assessments was administered. Results: Analysis revealed intact abilities across all 4 cases on measures of general language, including receptive language, expressive language, receptive vocabulary and naming. While 2 of the 4 cases also demonstrated intact high-level language skills across all measures, the remaining 2 demonstrated specific deficits in linguistic problem solving at 6 months after treatment. Follow-up assessment of 1 case also demonstrated further decline in this area 12 months later. Conclusion: Findings of high-level language deficits in problem solving in 2 of the 4 cases examined supported previous reports of specific impairments in high-level language and in thinking flexibility and problem solving following cerebellar hemispheric damage in childhood. Copyright (c) 2007 S. Karger AG, Basel