The value of perfusion computed tomography in predicting clinically relevant vasospasm in patients with aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia remains a severe potential complication of aneurysmal subarachnoid hemorrhage (SAH) possibly leading to death and disability. We evaluated a semiquantitative and visual analysis of perfusion computed tomography (PCT) as a predictor of clinically relevant vasospasm (CRV) in patients with aneurysmal SAH. Thirty-eight patients with aneurysmal SAH were analyzed yielding 145 PCT scans. PCT, clinical examination, and transcranial Doppler ultrasound (TCD) were performed on days 3, 7, 10, and 14 after hemorrhage. Cerebral blood flow, cerebral blood volume, and time to peak (TTP) were analyzed semiquantitatively using six regions of interest, and visually for signs of cerebral hypoperfusion. CRV was defined as secondary cerebral infarction (CI) seen on cranial computed tomography scans and/or delayed neurological deterioration (DND). CI occurred in 13 (34.2 %) and DND in 11 patients (28.9 %). With TCD as pretest, TTP had a sensitivity of 90 % and a specificity of 72 % (cutoff value, 0.963) as predictor for CI. TTP’s sensitivity as predictor for DND was 90 % with a specificity of 61.1 % (cutoff value, 0.983). Visual analysis of TTP showed a negative predictive value of 100 % with a positive predictive value of 52 %. TTP is a sensitive and specific perfusion parameter in predicting CI in patients with SAH. Its use in the clinical setting may optimize the early treatment of patients at risk for vasospasm before the onset of clinical deterioration, especially when applying TCD as pretest. Further investigation in a larger patient population is required.     

Autism in community pre-schoolers: Developmental profiles

Autism is often a complex developmental disorder. The aim of the present study was to describe the developmental characteristics of 129 1–4-year-old children (102 boys, 27 girls) referred for clinical assessment (mean age 2.9 years) due to suspicion of autism spectrum disorder (ASD) after community screening at Child Health Care centers. All children were clinically assessed at the Child Neuropsychiatry Clinic (CNC) in Gothenburg by a research team (neurodevelopmental examination, structured interviews and general cognitive and language examinations). Of the 129 children, 100 met diagnostic criteria for ASD (69 with autistic disorder, and 31 with atypical autism/pervasive developmental disorder-not otherwise specified). The remaining 29 children had a variety of developmental disorders, most often attention-deficit/hyperactivity disorder (ADHD), language disorder, borderline intellectual functioning, and intellectual developmental disorder (IDD) with (n = 25) or without (n = 4) autistic traits (AT). IDD was found in 36% of the 100 children with ASD, and in 4% of the 25 children with AT. Of the children with ASD, 56% had language disorder with no or just a few words at the initial assessment at the CNC, many of whom in combination with IDD. Hyperactivity was found in 37% of those with ASD and in 40% of those with AT. Epilepsy was found in 6% of the total group and in 7% of those with a diagnosis of ASD. Of the latter group 11% had a history of regression, while none of the AT cases had a similar background. When results were compared with a non-screened preschool ASD group of 208 children, referred for ASD intervention at a mean age of 3.4 years, very similar developmental profiles were seen. In conclusion, early community ASD screening appears to systematically identify those children who are in need of intervention and follow-up.     

Patient Safety Through RFID: Vulnerabilities in Recently Proposed Grouping Protocols

As RFID-tagged systems become ubiquitous, acceptance of this technology by the general public necessitates addressing related security/privacy issues. The past eight years have seen an increasing number of publications in this direction, specifically using cryptographic approaches. Recently, the Journal of Medical Systems published two papers addressing security/privacy issues through cryptographic protocols. We consider the proposed protocols and identify some existing vulnerabilities.     

The patients’ view: impact of the extent of resection,intraoperative imaging,and awake surgery on health-related quality of life in high-grade glioma patients—results of a multicenter cross-sectional study

Neurosurgical Review - The objective of the present study is to assess the influence of extent of resection (EoR), use of intraoperative imaging, and awake surgery on health-related quality of life...     

Alpha-methylacyl-CoA racemase (AMACR) expression in epithelial ovarian cancer

Alpha-methylacyl-CoA racemase (AMACR) is involved in the cellular metabolism of fatty acids. It is a prognostic factor in prostate and colorectal cancer. So far, little is known about its expression and prognostic role in ovarian cancer. We investigated the expression of AMACR in a total of 420 ovarian tumors (388 carcinomas, 32 borderline tumors) by immunohistochemistry on tissue microarrays of two independent patient cohorts. In both cohorts, cytoplasmic AMACR expression was identified in 11.8% (16/136) and 5.4% (13/239), respectively, of the ovarian carcinomas. In contrast, borderline tumors did not show any AMACR expression. AMACR expression was significantly associated with histological subtype, FIGO stage, and grade in one cohort and low estrogen receptor levels in the other cohort. In univariate analysis, AMACR expression was significantly associated with poor overall survival (log rank, p = 0.006) and an independent prognostic factor in a multivariate analysis (HR 3.3; CI 1.3–7.9; p = 0.008) but could not be verified in the second cohort. Unlike in other tumor entities, AMACR expression does not seem to have an unequivocal prognostic impact in ovarian cancer. The prevalence may limit the value of AMACR for the differential diagnosis between metastatic colorectal carcinomas and primary ovarian carcinomas, whereas the association with estrogen receptor expression deserves further studies.     

Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins

Enterohemorrhagic Escherichia coli (EHEC) is one of the leading causes of bacterial enteric infections worldwide, causing ∼100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States alone. These illnesses have been linked to consumption of contaminated animal products and vegetables. Currently, other than thermal inactivation, there are no effective methods to eliminate pathogenic bacteria in food. Colicins are nonantibiotic antimicrobial proteins, produced by E. coli strains that kill or inhibit the growth of other E. coli strains. Several colicins are highly effective against key EHEC strains. Here we demonstrate very high levels of colicin expression (up to 3 g/kg of fresh biomass) in tobacco and edible plants (spinach and leafy beets) at costs that will allow commercialization. Among the colicins examined, plant-expressed colicin M had the broadest antimicrobial activity against EHEC and complemented the potency of other colicins. A mixture of colicin M and colicin E7 showed very high activity against all major EHEC strains, as defined by the US Department of Agriculture/Food and Drug Administration. Treatments with low (less than 10 mg colicins per L) concentrations reduced the pathogenic bacterial load in broth culture by 2 to over 6 logs depending on the strain. In experiments using meats spiked with E. coli O157:H7, colicins efficiently reduced the population of the pathogen by at least 2 logs. Plant-produced colicins could be effectively used for the broad control of pathogenic E. coli in both plant- and animal-based food products and, in the United States, colicins could be approved using the generally recognized as safe (GRAS) regulatory approval pathway.Enterohemorrhagic Escherichia coli (EHEC), a subset of Shiga toxin-producing E. coli (STEC) strains, is a leading cause of bacterial enteric infections in the United States and worldwide. EHEC causes ∼100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States alone (1). Most of these illnesses have been linked to consumption of foods derived from animal products and, recently, organically grown vegetables. Nearly a quarter of all documented cases of EHEC in the United States last year were associated with fruits and vegetables, especially organically grown produce (www.cdc.gov/foodsafety/pdfs/foodborne-disease-outbreaks-annual-report-2013-508c.pdf). Although O157:H7 is currently the predominant serotype and accounts for ∼75% of EHEC infections worldwide, several non-O157 EHEC serotypes are also emerging as serious concerns for foodborne illnesses. In the United States, a group often referred to as the “Big 6” (O111, O26, O121, O103, O145, and O45) accounts for the majority of the non-O157:H7 serotypes isolated from clinical infections and, therefore, is also a focus of concern (2). One of the most serious recent cases of E. coli contamination outside the United States occurred in Europe in 2011, when fenugreek seeds contaminated with O104:H4 E. coli in an organic sprouts farm afflicted nearly 4,000 people, ultimately causing 54 deaths (3).Currently, there are very few interventions targeted toward the inactivation of bacteria on food. Most of the available interventions involve heating or organic acids, which can adversely modify the taste and quality of the products. Currently approved bacteriophage mixtures enable narrow and specific control of O157:H7 but not of other pathogenic strains (4). Use of traditional antibiotics for the treatment of food is not appropriate and should be considered unacceptable, particularly due to the increase of antibiotic resistance seen among E. coli strains found in food (5). Among nonantibiotic antibacterials, several colicins have been shown to be highly effective against some EHEC strains, each individually reducing the bacterial load by up to 5 logs; some of them were found to be an effective treatment for reducing EHEC populations in both live animals and animal-derived products (6, 7).Colicins are a group of bacteriocin-class antimicrobial proteins produced by, and effective against, E. coli and very closely related bacteria. Research on colicins began with their initial discovery 90 y ago (8). Colicins are classified based on their mode of bactericidal activity (either enzymatic inhibition of DNA, RNA, or cell-wall synthesis or depolarization via a pore-forming effect), their membrane receptors, and the mechanism they use for translocation through the outer membrane and across the periplasmic space of gram-negative bacteria. There are limited data on the effects of colicins on major foodborne E. coli strains (e.g., 7, 9, 10). We demonstrate here that we were able to express most colicins in plants with very high yields (up to 30% of total soluble protein, or 3 g active protein per kg of fresh green biomass) and at manufacturing costs that would allow commercial adoption of the technology. Production host plants can include tobacco and edible species such as spinach and leafy beets. Among the different colicins evaluated, colicin M was found to possess the broadest antimicrobial activity against major pathogenic E. coli strains. Because of their different mechanisms of action, mixtures of colicins can be used to exert complementary (additive) control of pathogens. Mixtures of colicin M and other colicins, and of colicin M and colicin E7 in particular, show very high activity against all seven pathogenic serotypes defined by the United States Department of Agriculture (USDA)/Food and Drug Administration (FDA) as major foodborne pathogens. These mixtures were also effective in controlling the emerging pathogenic serotype O104:H4. Treatments with colicin mixtures at low levels (nanomolar concentrations, or less than 10 mg total colicins per kg of treated food product) reduce the bacterial load of different pathogenic strains by 2 to >6 logs.We propose using plant-produced colicins on food to enable broad control of pathogenic E. coli bacteria in animal- and plant-derived products. Because the compositions of plant-produced colicins are identical to those of native colicins produced by colicinogenic strains in many environments, including the gastrointestinal (GI) tract of humans and other animals, colicins are recognized as safe through an extensive history of human exposure, and therefore in the United States they can be approved using the GRAS (generally recognized as safe) regulatory approval pathway.     

Dental MRI: Imaging of soft and solid components without ionizing radiation

Purpose:

To evaluate the ability of conventional and ultra‐short or zero echo time MRI for imaging of soft and solid dental components in and ex vivo.

Materials and Methods:

Turbo spin echo (TSE), ultra‐short echo time (UTE), and zero echo time (ZTE) MRI were performed on extracted (human and equine) teeth and in vivo using whole‐body and small‐bore MR systems at 3 T, 7T, and 9.4T, respectively.

Results:

At an isotropic resolution of (600 μm)³, strong signal of soft‐tissue, e.g., mucosa and nerves with excellent contrast was achieved using TSE at 3T in vivo. No signal, though, was obtained from solid components, e.g., teeth (due to short T₂). In contrast, dentin, cementum as well as enamel of extracted teeth were readily depicted using UTE and ZTE at a resolution of ≈ (150 μm)³ at 7T and 9.4T. In particular, ZTE provided higher signal in enamel.

Conclusion:

As an alternative to X‐ray based methods like cone‐beam computed tomography (CT) or conventional CT, the presented results demonstrate the potential of ZTE and UTE MRI as a radiation‐free imaging modality, delivering contrast of soft and solid components at the same time. J. Magn. Reson. Imaging 2012;36:841–846. © 2012 Wiley Periodicals, Inc.     

Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata

Alopecia areata (AA) is a common hair loss disorder, which is thought to be a tissue-specific autoimmune disease. Previous research has identified a few AA susceptibility genes, most of which are implicated in autoimmunity. To identify new genetic variants and further elucidate the genetic basis of AA, we performed a genome-wide association study using the strategy of pooled DNA genotyping (729 cases, 656 controls). The strongest association was for variants in the HLA region, which confirms the validity of the pooling strategy. The selected top 61 single-nucleotide polymorphisms (SNPs) were analyzed in an independent replication sample (454 cases, 1364 controls). Only one SNP outside of the HLA region (rs304650) showed significant association. This SNP was then analyzed in a second independent replication sample (537 cases, 657 controls). The finding was not replicated on a significant level, but showed the same tendency. A combined analysis of the two replication samples was then performed, and the SNP rs304650 showed significant association with P=3.43 × 10(-4) (OR=1.24 (1.10-1.39)). This SNP maps to an intronic region of the SPATA5 (spermatogenesis-associated protein 5) gene on chromosome 4. The results therefore suggest the SPATA5 locus is a new susceptibility locus for AA.