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

Development, implementation, and pilot study of a sentinel network ("The Watchtowers") for monitoring emergency primary health care activity in Norway

<p>Abstract</p> <p>Background</p> <p>In Norway there is a shortage of valid health activity statistics from the primary care out-of-hours services and the pre-hospital emergency health care system. There is little systematic information available because data registration is lacking or is only recorded periodically, and definitions of variables are not consistent.</p> <p>Method</p> <p>A representative sample of Norwegian municipalities and out-of-hours districts was contracted to establish a sentinel network, "The Watchtowers", and procedures were developed for collecting continuous data from out-of-hours services. All contacts, either per telephone or direct attendance, are recorded during day and night. The variables are registered in a computer program developed by the National Centre for Emergency Primary Health Care, and sent by email in Excel-file format to the Centre on a monthly basis.</p> <p>Results</p> <p>The selection process yielded a group of 18 municipalities, with a fair degree of representativeness for Norwegian municipalities as a whole. The sample has 212,921 inhabitants, which constitutes 4.6% of the total Norwegian population. During a pilot period lasting three months the Watchtowers recorded all individual contacts. The procedures for registration, submitting and checking data worked satisfactorily. There was little data missing, and during the last three months of 2006 a total of 23,346 contacts were registered.</p> <p>Conclusion</p> <p>We have been able to establish a sentinel network with a fair degree of representativeness for Norwegian out-of-hours districts and municipalities. The data collected reflect national activities from casualty clinics in Norway. Such data are useful for both research and system improvements.</p

Psychiatry out-of-hours: a focus group study of GPs' experiences in Norwegian casualty clinics

Background: For Norwegian general practitioners (GPs), acute treatment of mental illness and substance abuse are among the most commonly experienced emergency situations in out-of-hours primary healthcare. The largest share of acute referrals to emergency psychiatric wards occurs out-of-hours, and out-of-hours services are responsible for a disproportionately high share of compulsory referrals. Concerns exist regarding the quality of mental healthcare provided in the out-of-hours setting. The aim of this study was to explore which challenges GPs experience when providing emergency care out-of-hours to patients presenting problems related to mental illness or substance abuse. Methods: We conducted a qualitative study based on two individual interviews and six focus groups with purposively sampled GPs (totally 45 participants). The interviews were analysed successively in an editing style, using a thematic approach based on methodological descriptions by Charmaz and Malterud. Results: Safety and uncertainty were the dominating themes in the discussions. The threat to personal safety due to unpredictable patient behaviour was a central concern, and present security precautions in the out-of-hours services were questioned. The GPs expressed high levels of uncertainty in their work with patients presenting problems related to mental illness or substance abuse. The complexity of the problems presented, shortage of time, limited access to reliable information and limited range of interventions available during out-of-hours contributed to this uncertainty. Perceived access to second opinion seemed to have a major impact on subjectively experienced work stress. Conclusions: The GPs experienced out-of-hours psychiatry as a field with high levels of uncertainty and limited support to help them meet the experienced challenges. This might influence the quality of care provided. If the current organisation of emergency mental healthcare is to be kept, we need to provide GPs with a better support framework out-of-hours

Walk-ins seeking treatment at an emergency department or general practitioner out-of-hours service: a cross-sectional comparison

Background Emergency Departments (ED) in Switzerland are faced with increasing numbers of patients seeking non-urgent treatment. The high rate of walks-ins with conditions that may be treated in primary care has led to suggestions that those patients would best cared for in a community setting rather than in a hospital. Efficient reorganisation of emergency care tailored to patients needs requires information on the patient populations using the various emergency services currently available. The aim of this study is to evaluate the differences between the characteristics of walk-in patients seeking treatment at an ED and those of patients who use traditional out-of-hours GP (General Practitioner) services provided by a GP-Cooperative (GP-C). Methods In 2007 and 2009 data was collected covering all consecutive patient-doctor encounters at the ED of a hospital and all those occurring as a result of contacting a GP-C over two evaluation periods of one month each. Comparison was made between a GP-C and the ED of the Waid City Hospital in Zurich. Patient characteristics, time and source of referral, diagnostic interventions and mode of discharge were evaluated. Medical problems were classified according to the International Classification of Primary Care (ICPC-2). Patient characteristics were compared using non-parametric tests and multiple logistic regression analysis was applied to investigate independent determinants for contacting a GP-C or an ED. Results Overall a total of 2974 patient encounters were recorded. 1901 encounters were walk-ins and underwent further analysis (ED 1133, GP-C 768). Patients consulting the GP-C were significantly older (58.9 vs. 43.8 years), more often female (63.5 vs. 46.9%) and presented with non-injury related medical problems (93 vs. 55.6%) in comparison with patients at the ED. Independent determining factors for ED consultation were injury, male gender and younger age. Walk-in distribution in both settings was equal over a period of 24 hours and most common during daytime hours (65%). Outpatient care was predominant in both settings but significantly more so at the GP-C (79.9 vs. 85.7%). Conclusions We observed substantial differences between the two emergency settings in a non gate-keeping health care system. Knowledge of the distribution of diagnoses, their therapy, of diagnostic measures and of the factors which determine the patients' choice of the ED or the GP-C is essential for the efficient allocation of resources and the reduction of costs

Safety measures to prevent workplace violence in emergency primary care centres - a cross-sectional study

Background: Employees in emergency primary care centres (EPCC) have raised personal safety as an issue. Despite a high risk of experiencing workplace violence at EPCCs in Norway, knowledge regarding applied preventive measures is limited. The description of existing safety measures is an important prerequisite to evaluate and make guidelines for the improvement of preventive practices on a national level. The objective of this study was to investigate to which extent general practitioners work alone in EPCCs in Norway, and to estimate the prevalence of other preventive measures against workplace violence. Methods: A survey was sent to the managers of all 210 registered EPCCs in Norway. The questionnaire included 22 items on safety measures, including available staff, architecture and outfitting of the reception and consulting rooms, and the availability of electronic safety systems and training or monitoring systems. The data were analysed using descriptive statistics. Differences between EPCCs staffed by one general practitioner alone and EPCCs with more health personnel on duty were explored. Results: Sixty-one (30%) of the 203 participating EPCCs had more than one person on duty round-the-clock. These EPCCs reported the application of a significantly higher number of safety measures compared to the EPCCs with only one general practitioner on duty during some or part of the 24 hours. Examples of safety measures being more common in highly staffed EPCCs were automatic door locks (p < 0.001), arrangement of furniture in the consulting room ensuring that the patient is not seated between the clinician and the exit (p = 0.014), the possibility of bringing an extra person on emergency call-outs or home visits when needed for security reasons (p = 0.014), and having organised training regarding violence (p < 0.001). Conclusion: This study shows considerable differences between Norwegian EPCCs regarding applied preventive measures, and a higher prevalence of such measures in EPCCs staffed with several health personnel around-the -clock. More research is needed to understand the reasons for, and the effects of, these differences

Human chitotriosidase-catalyzed hydrolysis of chitosan

acceptedVersio