Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus ...faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting.
The criterion standard to diagnose and classify cranial DAVFs is DSA. Since this is invasive, relatively expensive and time-consuming, a noninvasive alternative is of interest. We aimed to evaluate ...the capabilities and pitfalls of 4D-CTA in a consecutive series of patients who presented with a newly diagnosed cranial DAVF, as demonstrated by conventional DSA.
Eleven patients were included in this study after biplane DSA demonstrated a cranial DAVF. They subsequently underwent 4D-CTA imaging by using a 320-detector CT scanner. DSA and 4D-CTA studies were independently read by 2 blinded observers, by using a standardized scoring sheet. 4D-CTA results were analyzed with DSA as the criterion standard.
In 10 cases, there was full agreement between DSA and 4D-CTA regarding the Borden classification. However, in the remaining patient, a slow-filling DAVF with a low shunt volume was missed by both readers on 4D-CTA. In all 10 detected cases, ≥ 1 of the major contributing arteries could be identified with 4D-CTA. Although, by using DSA, the 2 observers identified additional arterial feeders in 7 and 8 cases, respectively, these discrepancies did not influence clinical decision making.
Although novel 4D-CTA imaging may not rule out a small slow-flow DAVF, it appears to be a valuable new adjunct in the noninvasive diagnostic work-up, treatment planning, and follow-up of patients with cranial DAVFs.
Stem-cell-derived organoids recapitulate in vivo physiology of their original tissues, representing valuable systems to model medical disorders such as infectious diseases. Cryptosporidium, a ...protozoan parasite, is a leading cause of diarrhoea and a major cause of child mortality worldwide. Drug development requires detailed knowledge of the pathophysiology of Cryptosporidium, but experimental approaches have been hindered by the lack of an optimal in vitro culture system. Here, we show that Cryptosporidium can infect epithelial organoids derived from human small intestine and lung. The parasite propagates within the organoids and completes its complex life cycle. Temporal analysis of the Cryptosporidium transcriptome during organoid infection reveals dynamic regulation of transcripts related to its life cycle. Our study presents organoids as a physiologically relevant in vitro model system to study Cryptosporidium infection.
The Gram-positive bacterium Enterococcus faecium is an important cause of nosocomial infections in immunocompromized patients.
We present a pyrosequencing-based comparative genome analysis of seven ...E. faecium strains that were isolated from various sources. In the genomes of clinical isolates several antibiotic resistance genes were identified, including the vanA transposon that confers resistance to vancomycin in two strains. A functional comparison between E. faecium and the related opportunistic pathogen E. faecalis based on differences in the presence of protein families, revealed divergence in plant carbohydrate metabolic pathways and oxidative stress defense mechanisms. The E. faecium pan-genome was estimated to be essentially unlimited in size, indicating that E. faecium can efficiently acquire and incorporate exogenous DNA in its gene pool. One of the most prominent sources of genomic diversity consists of bacteriophages that have integrated in the genome. The CRISPR-Cas system, which contributes to immunity against bacteriophage infection in prokaryotes, is not present in the sequenced strains. Three sequenced isolates carry the esp gene, which is involved in urinary tract infections and biofilm formation. The esp gene is located on a large pathogenicity island (PAI), which is between 64 and 104 kb in size. Conjugation experiments showed that the entire esp PAI can be transferred horizontally and inserts in a site-specific manner.
Genes involved in environmental persistence, colonization and virulence can easily be aquired by E. faecium. This will make the development of successful treatment strategies targeted against this organism a challenge for years to come.
Background
Interactions with professional caregivers affect the quality of support and life of people with intellectual disabilities and contribute to the occurrence of challenging behaviour. The ...present literature review provides an overview of factors facilitating or hindering meaningful staff–client interactions in people with borderline to profound intellectual disabilities and challenging behaviour.
Method
Database searches, reference list and citation screening, and expert consultations were undertaken. A thematic synthesis of 28 studies was performed.
Results
Factors were identified at the client (i.e. behaviour, emotions and (dis)abilities), staff (i.e. interactive principles, knowledge, psychological resources, attributions, attitudes and (coping with) emotions) and context levels (i.e. group size, team and organization).
Conclusions
The present overview provides insights into factors that facilitate or hinder meaningful staff–client interactions with people with intellectual disabilities and challenging behaviour. The results support the need to combine client, staff and contextual factors when considering staff–client interactions in research and practice.
Ampicillin resistance is a marker for hospital-associated Enterococcus faecium. Feces from 208 dogs were selectively screened for the occurrence of ampicillin-resistant E. faecium (AREF). AREF was ...detected in 42 (23%) of 183 dogs screened in a cross-sectional study in the United Kingdom and in 19 (76%) of 25 dogs studied longitudinally in Denmark. AREF carriage was intermittent in all dogs studied longitudinally. Multilocus sequence typing of 63 canine AREF isolates revealed the presence of 13 distinct sequence types. Approximately 76% of the isolates belonged to hospital-adapted clonal complex 17 (CC17), including those of sequence types ST-78 and ST-192, which are widespread in European and Asian hospitals. Longitudinal screening of 18 healthy humans living in contact with 13 of the dogs under study resulted in the identification of a single, intermittent CC17 carrier. This person carried one of the sequence types (ST-78) recovered from his dog. Based on PCR and Southern hybridization analyses, the putative virulence gene cluster from orf903 to orf907 was widespread in canine AREF isolates (present in 97%), whereas orf2351 (present in 26% of isolates) and orf2430 (present in 31%) were strongly associated with CC17-related sequence types (P < 0.05). Surprisingly, esp and hyl were not detected in any of the isolates. The antimicrobial resistance profiles of canine AREF isolates generally differed from those previously described for clinical human isolates. The results indicate that dogs are frequent carriers of CC17-related lineages and may play a role in the spread of this nosocomial pathogen. The distinctive virulence and antimicrobial resistance profiles observed among canine AREF isolates raise interesting questions about the origin and evolution of the strains causing human infections.
Background
The purpose of awake brain tumor surgery is to maximize the resection of the tumor and to minimize the risk of neurological and cognitive impairments. The aim of this study is to gain ...understanding of the development of possible postoperative cognitive deficits after awake brain tumor surgery in patients with suspected gliomas, by comparing preoperative, early postoperative, and late postoperative functioning. A more detailed timeline will be helpful in informing candidates for surgery about what to expect regarding their cognitive functioning.
Methods
Thirty-seven patients were included in this study. Cognitive functioning was measured by means of a broad cognitive screener preoperatively, days after surgery and months after surgery in patients who underwent awake brain tumor surgery with cognitive monitoring. The cognitive screener included tests for object naming, reading, attention span, working memory, inhibition, inhibition/switching, and visuoperception. We performed a Friedman ANOVA to analyze on group level.
Results
Overall, no significant differences were found between preoperative cognitive functioning, early postoperative cognitive functioning, and late postoperative cognitive functioning, except for performances on the inhibition task. Directly after surgery, patients were significantly slower on this task. However, in the following months after surgery, they returned to their preoperative level.
Conclusion
The timeline of cognitive functioning after awake tumor surgery appeared overall stable in the early and late postoperative phase, except for inhibition, which is more difficult in the first days after awake brain tumor surgery. This more detailed timeline of cognitive functioning, in combination with future research, can possibly be contributing in informing patients and caregivers what to expect after awake brain tumor surgery.
Endovascular Treatment of Epistaxis Willems, P.W.A; Farb, R.I; Agid, R
American journal of neuroradiology : AJNR,
10/2009, Volume:
30, Issue:
9
Journal Article
Peer reviewed
Open access
Epistaxis is a common condition that can be managed conservatively in most cases. When these measures, including anterior and posterior packing of the nasal cavity, are unsuccessful at controlling ...the bleeding, interruption of the blood supply to the sinonasal area can be performed, either by surgical ligation or by transarterial embolization. Embolization should be preceded by thorough diagnostic angiography. Aside from aiding with subsequent selective catheterization and embolization, such angiography may reveal significant anatomic anomalies, anastomoses, or an unsuspected cause of epistaxis. Taking these findings into account, the interventionalist may decide to refrain from embolization or adjust the technique to minimize the risk of adverse events, which are mostly related to inadvertent embolization of the internal carotid artery or ophthalmic artery. We present a review of the various causes of epistaxis and the treatment options, with emphasis on endovascular embolization. We also describe the protocol of our institution for endovascular management of this condition.
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