Neuroanatomical correlates of locative prepositions

Very little research has explored which neural systems may be important for retrieving the meanings of locative prepositions (e.g., in, on, around). To begin to address this knowledge gap, we conducted a lesion study in which we tested the hypothesis that processing the meanings of locative prepositions depends on neural structures in the left inferior prefrontal cortex and left inferior parietal cortex. Seventy‐eight subjects with focal, stable lesions to various parts of the telencephalon and a comparison group of 60 normal participants were studied with tasks that require production, comprehension, and semantic analysis of locative prepositions. In support of our hypothesis, we found that in subjects with impaired knowledge of locative prepositions, the highest region of lesion overlap was in the left frontal operculum and the left supramarginal gyrus, and in the white matter subjacent to these two areas. In a second study, focused on six subjects who had pervasive defects for locative preposition knowledge, we confirmed that such defects were associated specifically with damage to the posterior left frontal operculum, white matter subjacent to this region, and white matter underneath the inferior parietal operculum. These subjects did not have basic impairments in spatial processing or working memory, and they had relatively well‐preserved processing of conceptual knowledge for actions and various categories of concrete entities (e.g., persons, animals, tools). All six subjects, however, had defects in naming actions, and some of them also had defective naming of some categories of concrete entities. Overall, the findings converge nicely with recent results from functional imaging approaches, and with classic studies from the aphasia‐based literature, and suggest that the left inferior prefrontal and left inferior parietal regions have crucial–albeit not exclusive–roles in processing knowledge associated with locative prepositions.     

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization

Bacteria causing infections in hospitalized patients are increasingly antibiotic resistant. Classical infection control practices are only partially effective at preventing spread of antibiotic-resistant bacteria within hospitals. Because the density of intestinal colonization by the highly antibiotic-resistant bacterium vancomycin-resistant Enterococcus (VRE) can exceed 10⁹ organisms per gram of feces, even optimally implemented hygiene protocols often fail. Decreasing the density of intestinal colonization, therefore, represents an important approach to limit VRE transmission. We demonstrate that reintroduction of a diverse intestinal microbiota to densely VRE-colonized mice eliminates VRE from the intestinal tract. While oxygen-tolerant members of the microbiota are ineffective at eliminating VRE, administration of obligate anaerobic commensal bacteria to mice results in a billionfold reduction in the density of intestinal VRE colonization. 16S rRNA gene sequence analysis of intestinal bacterial populations isolated from mice that cleared VRE following microbiota reconstitution revealed that recolonization with a microbiota that contains Barnesiella correlates with VRE elimination. Characterization of the fecal microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation demonstrated that intestinal colonization with Barnesiella confers resistance to intestinal domination and bloodstream infection with VRE. Our studies indicate that obligate anaerobic bacteria belonging to the Barnesiella genus enable clearance of intestinal VRE colonization and may provide novel approaches to prevent the spread of highly antibiotic-resistant bacteria.     

Ritual Circumcision in the Age of Germ Theory Amongst Nineteenth-Century New York Immigrants

While Jewish ritual circumcision continues to be a controversial issue in Europe and the US, metzitzah b’peh, the addendum to brit milah, which requires the mohel (ritual peritomist) to orally suck blood from the wound immediately following the excision of the foreskin, remains a divisive topic. While medical historians have studied European outbreaks of infectious disease following metzitzah b’peh, no one has assessed the response of the nineteenth century New York Jewry. This paper analyses how this nascent community responded to the thorough report by the New York Board of Health following an alleged and discredited outbreak of syphilis attributed to metzitzah b’peh in 1873, especially in the context of nineteenth century immigration, popular perception of syphilis and American medicine. Keywords : Ritual Circumcision, Metzitzah b’peh, Syphilis, Syphilophobia, Mohel, Lower East Side     

Lateral Impact Validation of a Geometrically Accurate Full Body Finite Element Model for Blunt Injury Prediction

This study presents four validation cases of a mid-sized male (M50) full human body finite element model—two lateral sled tests at 6.7 m/s, one sled test at 8.9 m/s, and a lateral drop test. Model results were compared to transient force curves, peak force, chest compression, and number of fractures from the studies. For one of the 6.7 m/s impacts (flat wall impact), the peak thoracic, abdominal and pelvic loads were 8.7, 3.1 and 14.9 kN for the model and 5.2 ± 1.1 kN, 3.1 ± 1.1 kN, and 6.3 ± 2.3 kN for the tests. For the same test setup in the 8.9 m/s case, they were 12.6, 6, and 21.9 kN for the model and 9.1 ± 1.5 kN, 4.9 ± 1.1 kN, and 17.4 ± 6.8 kN for the experiments. The combined torso load and the pelvis load simulated in a second rigid wall impact at 6.7 m/s were 11.4 and 15.6 kN, respectively, compared to 8.5 ± 0.2 kN and 8.3 ± 1.8 kN experimentally. The peak thorax load in the drop test was 6.7 kN for the model, within the range in the cadavers, 5.8–7.4 kN. When analyzing rib fractures, the model predicted Abbreviated Injury Scale scores within the reported range in three of four cases. Objective comparison methods were used to quantitatively compare the model results to the literature studies. The results show a good match in the thorax and abdomen regions while the pelvis results over predicted the reaction loads from the literature studies. These results are an important milestone in the development and validation of this globally developed average male FEA model in lateral impact.     

Candida guilliermondii and Other Species of Candida Misidentified as Candida famata: Assessment by Vitek 2, DNA Sequencing Analysis,and Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry in Two Global Antifungal Surveillance Programs

Candida famata (teleomorph Debaryomyces hansenii) has been described as a medically relevant yeast, and this species has been included in many commercial identification systems that are currently used in clinical laboratories. Among 53 strains collected during the SENTRY and ARTEMIS surveillance programs and previously identified as C. famata (includes all submitted strains with this identification) by a variety of commercial methods (Vitek, MicroScan, API, and AuxaColor), DNA sequencing methods demonstrated that 19 strains were C. guilliermondii, 14 were C. parapsilosis, 5 were C. lusitaniae, 4 were C. albicans, and 3 were C. tropicalis, and five isolates belonged to other Candida species (two C. fermentati and one each C. intermedia, C. pelliculosa, and Pichia fabianni). Additionally, three misidentified C. famata strains were correctly identified as Kodomaea ohmeri, Debaryomyces nepalensis, and Debaryomyces fabryi using intergenic transcribed spacer (ITS) and/or intergenic spacer (IGS) sequencing. The Vitek 2 system identified three isolates with high confidence to be C. famata and another 15 with low confidence between C. famata and C. guilliermondii or C. parapsilosis, displaying only 56.6% agreement with DNA sequencing results. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) results displayed 81.1% agreement with DNA sequencing. One strain each of C. metapsilosis, C. fermentati, and C. intermedia demonstrated a low score for identification (<2.0) in the MALDI Biotyper. K. ohmeri, D. nepalensis, and D. fabryi identified by DNA sequencing in this study were not in the current database for the MALDI Biotyper. These results suggest that the occurrence of C. famata in fungal infections is much lower than previously appreciated and that commercial systems do not produce accurate identifications except for the newly introduced MALDI-TOF instruments.     

Rapid and Reliable Identification of Staphylococcus aureus Capsular Serotypes by Means of Artificial Neural Network-Assisted Fourier Transform Infrared Spectroscopy

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors and represent putative targets for vaccine development. Therefore, the purpose of this study was to develop a high-throughput method to identify and discriminate the clinically important S. aureus capsular serotypes 5, 8, and NT (nontypeable). A comprehensive set of clinical isolates derived from different origins and control strains, representative for each serotype, were used to establish a CP typing system based on Fourier transform infrared (FTIR) spectroscopy and chemometric techniques. By combining FTIR spectroscopy with artificial neuronal network (ANN) analysis, a system was successfully established, allowing a rapid identification and discrimination of all three serotypes. The overall accuracy of the ANN-assisted FTIR spectroscopy CP typing system was 96.7% for the internal validation and 98.2% for the external validation. One isolate in the internal validation and one isolate in the external validation failed in the classification procedure, but none of the isolates was incorrectly classified. The present study demonstrates that ANN-assisted FTIR spectroscopy allows a rapid and reliable discrimination of S. aureus capsular serotypes. It is suitable for diagnostic as well as large-scale epidemiologic surveillance of S. aureus capsule expression and provides useful information with respect to chronicity of infection.