The presence of genes encoding for different virulence factors in clonally related Escherichia coli that produce CTX-Ms

Successful international clones have recently emerged among Escherichia coli that produce CTX-M β-lactamases as important causes of community-onset urinary tract and bloodstream infections. One hundred and seven isolates that belong to sequence types (STs) ST38, ST131, ST405, ST648, and 38 nonrelated CTX-M-producing E. coli from Canada and the Netherlands were assigned to phylogenetic groups and tested for the presence of genes encoding for virulence factors (VFs) using established multiplex polymerase chain reaction. The STs E. coli were significantly more resistant to antibiotics--ST38, ST405, and ST648 belonged to phylogenetic group D while ST131 belonged to B2. Secreted autotransporter toxin (sat), aerobactin receptor, and pathogenicity island marker were significantly more common among the STs; the heat-resistant agglutinin (hra) was present in ST38, sat, and uropathogenic-specific protein, and putative adhesin-siderophore receptor was more common in ST131, while outer membrane protease T was present in ST648. ST131 had a significantly higher VF score. In conclusion, the precise role of these VFs remains to be elucidated; however, we have identified certain putative VFs that possibly contribute to the fitness and success of certain sequence types.     

Inside guidelines: comparative analysis of recommendations and evidence in diabetes guidelines from 13 countries

OBJECTIVE: To compare guidelines on diabetes from different countries in order to examine whether differences in recommendations could be explained by use of different research evidence. RESEARCH DESIGN AND METHODS: We analyzed 15 clinical guidelines on type 2 diabetes from 13 countries using qualitative methods to compare the recommendations and bibliometric methods to measure the extent of overlap in citations used by different guidelines. A further qualitative analysis of recommendations and cited evidence for two specific issues in diabetes care explored the apparent discrepancy between recommendations and evidence. RESULTS: The recommendations made in the guidelines were in agreement about the general management of type 2 diabetes, with some important differences in treatment details. There was little overlap in evidence cited by the guidelines, with 18% (185/1,033) of citations shared with any other guideline, and only 10 studies (1%) appearing in six or more guidelines. The measurable overlap in evidence between guidelines increases if multiple publications from the same study and the use of reviews are taken into account. Research originating from the U.S. predominated (40% of citations); however, nearly all (11/12) guidelines were significantly more likely to cite evidence originating from their own countries. CONCLUSIONS: Despite the variation in cited evidence and preferential citation of evidence from a guideline's country of origin, we found a high degree of international consensus in recommendations made for the clinical care of type 2 diabetes. The influence of professional bodies such as the American Diabetes Association may be an important factor in explaining international consensus. Globalization of recommended management of diabetes is not a simple consequence of the globalization of research evidence.     

Cerebral pressure–flow relationship in lowlanders and natives at high altitude

We investigated if dynamic cerebral pressure–flow relationships in lowlanders are altered at high altitude (HA), differ in HA natives and after return to sea level (SL). Lowlanders were tested at SL (n=16), arrival to 5,050 m, after 2-week acclimatization (with and without end-tidal PO₂ normalization), and upon SL return. High-altitude natives (n=16) were tested at 5,050 m. Testing sessions involved resting spontaneous and driven (squat–stand maneuvers at very low (VLF, 0.05 Hz) and low (LF, 0.10 Hz) frequencies) measures to maximize blood pressure (BP) variability and improve assessment of the pressure–flow relationship using transfer function analysis (TFA). Blood flow velocity was assessed in the middle (MCAv) and posterior (PCAv) cerebral arteries. Spontaneous VLF and LF phases were reduced and coherence was elevated with acclimatization to HA (P<0.05), indicating impaired pressure–flow coupling. However, when BP was driven, both the frequency- and time-domain metrics were unaltered and comparable with HA natives. Acute mountain sickness was unrelated to TFA metrics. In conclusion, the driven cerebral pressure–flow relationship (in both frequency and time domains) is unaltered at 5,050 m in lowlanders and HA natives. Our findings indicate that spontaneous changes in TFA metrics do not necessarily reflect physiologically important alterations in the capacity of the brain to regulate BP.     

Changes in lymphoid organs and blood lymphocytes induced by vitamin A deficiency and Newcastle disease virus infection in chickens

The effect of vitamin A deficiency in the presence or absence of Newcastle disease virus infection (NDV, La Sota strain) on weight of lymphoid organs and on the number and type of circulating white blood cells (WBC) was investigated in chickens. Day-old chickens with limited vitamin A reserves were fed purified diets containing either marginal (ad libitum) or adequate (pair-fed) levels of vitamin A and at 21–28 days of age; half the chickens in each group were infected with NDV. Vitamin A deficiency resulted only in significantly lower absolute and relative weights of bursa of Fabricius and after infection both weights of bursa and thymus were significantly lower. Relative weight of spleen was significantly higher after infection irrespective of vitamin A status. Liver weights were not affected by vitamin A status and/or NDV infection. Both vitamin A deficiency and NDV infection resulted in lymphopenia, while the lowest number of WBC were observed in vitamin A-deficient chickens during the acute phase of NDV (5 days after infection). Subsequent to lymphopenia due to NDV infection, a marked lymphocytosis was observed in controls and to a lesser extent in vitamin A-deficient birds. These results indicate that vitamin A deficiency, which is aggravated by concomitant NDV infection, affects lymphoid cell systems.     

Transient structural distortion of metal-free Cu/Zn superoxide dismutase triggers aberrant oligomerization

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to the misfolding of Cu/Zn superoxide dismutase (SOD1). ALS-related defects in SOD1 result in a gain of toxic function that coincides with aberrant oligomerization. The structural events triggering oligomerization have remained enigmatic, however, as is the case in other protein-misfolding diseases. Here, we target the critical conformational change that defines the earliest step toward aggregation. Using nuclear spin relaxation dispersion experiments, we identified a short-lived (0.4 ms) and weakly populated (0.7%) conformation of metal-depleted SOD1 that triggers aberrant oligomerization. This excited state emanates from the folded ground state and is suppressed by metal binding, but is present in both the disulfide-oxidized and disulfide-reduced forms of the protein. Our results pinpoint a perturbed region of the excited-state structure that forms intermolecular contacts in the earliest nonnative dimer/oligomer. The conformational transition that triggers oligomerization is a common feature of WT SOD1 and ALS-associated mutants that have widely different physicochemical properties. But compared with WT SOD1, the mutants have enhanced structural distortions in their excited states, and in some cases slightly higher excited-state populations and lower kinetic barriers, implying increased susceptibility to oligomerization. Our results provide a unified picture that highlights both (i) a common denominator among different SOD1 variants that may explain why diverse mutations cause the same disease, and (ii) a structural basis that may aid in understanding how different mutations affect disease propensity and progression.     

Patients' priorities for ambulatory hospital care centres. A survey and discrete choice experiment among elderly and chronically ill patients of a Dutch hospital

Objective  This study established patients' preferences regarding the facilities in an adjacent centre for ambulatory hospital care. It also identified determinants of patients' choice to visit this centre instead of the regional hospital.
Methods  A questionnaire survey among 1477 elderly and chronically ill people (response 72%) assessed patients' expectations regarding (a) quality of hospital care, (b) facilities in centres for ambulatory hospital care, and (c) future use of these centres. Additionally, 75 patients participated in discrete choice experiments about their decision to visit a centre for ambulatory hospital care or the regional hospital.
Results  Respondents prioritized facilities for examination and medical consultations in the ambulatory care centres. Half of the respondents also valued paramedic care, information desks and pharmacies as centre facilities. Most patients living near a future centre for ambulatory care would rather visit this centre than the regional hospital. However, they favoured seeing their familiar physician, short waiting lists and appointments scheduled consecutively on 1 day. If these aspects were not guaranteed at the adjacent centres, more patients chose to visit the hospital.
Conclusions  Although patients value most facilities, they set clear priorities. Furthermore, this study showed three important conditions in the decision to visit an ambulatory care centre; (1) the possibility to see their familiar physician, (2) to have consecutive appointments, and (3) a short waiting list. These three factors were more important to patients than proximity. Thus, when choosing between a hospital and an adjacent centre for ambulatory care, quality aspects matter.     

Clinical and molecular characteristics of extended-spectrum-beta-lactamase-producing Escherichia coli causing bacteremia in the Rotterdam Area, Netherlands

We investigated the clinical and molecular characteristics of bacteremia caused by extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli over a 2-year period (2008 to 2009) in the Rotterdam region (including 1 teaching hospital and 2 community hospitals) of Netherlands. The majority of patients presented with community onset urinary and intra-abdominal infections, with an increase in prevalence during 2009. The majority of E. coli isolates produced CTX-M-15, and 4 sequence types (ST38, ST131, ST405, and ST648) predominated. There were significant differences in clinical and molecular characteristics between the 2 community hospitals.     

Arthrodesis of the first carpometacarpal joint: 33 cases of arthrosis

Thirty-three arthrodeses were performed for arthrosis of the first carpometacarpal joint in 29 patients. The patients were reexamined 5 (2-10) years after the operation. Twenty arthrodeses were clinically satisfactory, although two had failed to unite. Analysis of this group showed that a painless stiff carpometacarpal joint causes some functional impairment, considered negligible by most patients. The remaining 13 cases were unsatisfactory due to pain caused by arthrosis in the peritrapezoidal joints (7 cases), nonunion (4), radial nerve neuroma (1), and unknown reason (1).     

Treprostinil in advanced experimental pulmonary hypertension: beneficial outcome without reversed pulmonary vascular remodeling

INTRODUCTION: Beneficial effects of treprostinil, a stable prostacyclin analogue, were demonstrated in patients with pulmonary arterial hypertension (PAH). Although regression of pulmonary vascular remodeling has been suggested as therapeutic mechanism, its mode of action remains unknown. METHODS: Flow-associated PAH was created in rats by injection of monocrotaline (60 mg/kg) combined with an abdominal aortocaval shunt. Subsequently, rats were treated with subcutaneous treprostinil (50 ng/kg/min, treated; n = 8) or saline (untreated; n = 9). A control group underwent sham-surgery (n = 8). Animals were sacrificed at symptoms of cardiac failure, together with their matched controls. RESULTS: Dyspnea and weight loss determined the moment of sacrifice in 8/9 untreated animals (89%) versus in one of eight treated animals (13%; log-rank test survival curves; P = 0.02). Mean pulmonary arterial pressure increased in the model (42 +/- 2 mm Hg in untreated vs. 18 +/- 1 in controls; P < 0.01) and decreased by 8 mm Hg after therapy (34 +/- 3 mm Hg, P = 0.04 vs. untreated). No effects of treatment on right ventricular hypertrophy could be demonstrated. Quantitative morphometry of pre- and intra-acinar pulmonary arteries revealed no effects of treatment on vessel histopathology. CONCLUSIONS: Treprostinil treatment improved clinical course and ameliorated symptoms of heart failure in a model of advanced PAH. However, beneficial effects were not associated with reversed structural remodelling of the pulmonary vasculature.