Multiple-mouse magnetic resonance imaging with cryogenic radiofrequency probes for evaluation of brain development.

Multiple-mouse magnetic resonance imaging (MRI) increases scan throughput by imaging several mice simultaneously in the same magnet bore, enabling multiple images to be obtained in the same time as a single scan. This increase in throughput enables larger studies than otherwise feasible and is particularly advantageous in longitudinal study designs where frequent imaging time points result in high demand for MRI resources. Cryogenically-cooled radiofrequency probes (CryoProbes) have been demonstrated to have significant signal-to-noise ratio benefits over comparable room temperature coils for in vivo mouse imaging. In this work, we demonstrate implementation of a multiple-mouse MRI system using CryoProbes, achieved by mounting four such coils in a 30-cm, 7-Tesla magnet bore. The approach is demonstrated for longitudinal quantification of brain structure from infancy to early adulthood in a mouse model of Sanfilippo syndrome (mucopolysaccharidosis type III), generated by knockout of the Hgsnat gene. We find that Hgsnat-/- mice have regionally increased growth rates compared to Hgsnat+/+ mice in a number of brain regions, notably including the ventricles, amygdala and superior colliculus. A strong sex dependence was also noted, with the lateral ventricle volume growing at an accelerated rate in males, but several structures in the brain parenchyma growing faster in females. This approach is broadly applicable to other mouse models of human disease and the increased throughput may be particularly beneficial in studying mouse models of neurodevelopmental disorders.

C-reactive protein as a marker of complicated diverticulitis in patients on anti-inflammatory medications.

BACKGROUND: Diverticulitis is a common indication for surgical emergency room admission, often leading to abdominal computed tomography (CT) scanning for both diagnosis and staging. C-reactive protein (CRP) has been identified as a useful biomarker of inflammation. Aspirin and corticosteroids are known to down-regulate CRP production. In this study, we evaluated the usefulness of CRP as a biomarker for complicated diverticulitis and specifically in patients on anti-inflammatory medications: aspirin and corticosteroids. METHODS: We analyzed the medical records of patients diagnosed at one medical center during a two-year period, with left-sided diverticulitis, according to clinical data and CT scan. Disease severity was assessed by the Hinchey score using the radiological findings detected by CT. RESULTS: A total of 295 patients were included in the study. Two hundred and forty-three (82 %) were classified with uncomplicated (Hinchey 1a) and 52 (18 %) with complicated disease (Hinchey > 1a). Mean CRP levels were 133.5 and 63.5 mg/ml for those with complicated and uncomplicated disease, respectively (p < 0.001), and 139 and 60 mg/ml, respectively (p < 0.001) in the subgroup of patients taking aspirin (n = 61). For 14 patients on corticosteroid treatment, the difference in mean CRP levels for complicated and uncomplicated disease was not statistically significant. CRP > 90 mg/ml had 88 % sensitivity and 75 % specificity for complicated disease. CONCLUSIONS: The CRP level distinguished between complicated and uncomplicated disease among left-sided diverticulitis patients including those taking aspirin, but not among those on corticosteroid treatment.

Quantitative investigations of idiotypic antibodies. V. Factors affecting the persistence and replacement of clones of antibody-producing cells.

The effect of challenge by antigen on persistence of clones of antibody-producing cells and on the induction of new clones was investigated through quantitative measurements of idiotypic specificities. In each of nine rabbits idiotypic specificities present in the earliest bleedings were completely replaced after a few months; subsequent changes occurred much more slowly. On a quantitative basis the population of molecules used as immunogen always reacted most effectively with the homologous anti-idiotypic antiserum. Little effect of increased antigen dose on the rate of change of idiotype was observed. Even large amounts of antigen administered every 2 wk caused only gradual changes in idiotypic specificities. This was attributed either to more effective capture of antigen by memory cells, as compared to precursor cells, or to the induction of tolerance in those clones that were not expressed. In two of three rabbits on a monthly injection schedule, the idiotypic specificities identified underwent very slow changes over a period as long as 17 months. Changes occurred more rapidly when antigen was administered every 2 wk. In each of four rabbits investigated, all idiotypic specificities identified before a 5 month rest period were still present afterwards, indicating the survival of essentially all clones of antibody-producing cells during that interval. Quantitative inhibition data indicated that some new clones of cells were initiated.

High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice.

Detailed anatomical atlases can provide considerable interpretive power in studies of both human and rodent neuroanatomy. Here we describe a three-dimensional atlas of the mouse brain, manually segmented into 62 structures, based on an average of 32 mum isotropic resolution T(2)-weighted, within skull images of forty 12 week old C57Bl/6J mice, scanned on a 7 T scanner. Individual scans were normalized, registered, and averaged into one volume. Structures within the cerebrum, cerebellum, and brainstem were painted on each slice of the average MR image while using simultaneous viewing of the coronal, sagittal and horizontal orientations. The final product, which will be freely available to the research community, provides the most detailed MR-based, three-dimensional neuroanatomical atlas of the whole brain yet created. The atlas is furthermore accompanied by ancillary detailed descriptions of boundaries for each structure and provides high quality neuroanatomical details pertinent to MR studies using mouse models in research.

Wall shear rate in supra-aortic vessels: a factor for different atherosclerotic pattern?

BACKGROUND: Atherosclerotic lesions of the upper extremity arise three to five times more often at the origin of the left subclavian artery than on the right side. The aim of this study was to investigate, whether the hemodynamic forces (peak wall shear rate) in the large supra-aortic branches measured by MRI differ in healthy subjects. PATIENTS AND METHODS: Peak wall shear rate (WSR) and blood flow was assessed in the left carotid, left subclavian and innominate artery in ten healthy volunteers (5 females, mean age of 35.2 +/- 9 years) using high resolution (pixel size 0.6 mm 2) magnetic resonance imaging (MRI) flow velocity measurements. RESULTS: There is no difference between the maximum WSR of the three large supra-aortic vessels. Only within the proximal (327 +/- 132s-1) and distal wall (458 +/- 154s-1) of the innominate artery a significant difference (p = 0.011) of the WSR was found. CONCLUSION: The results from this study indicate that WSR is not different in the supra-aortic vessels. Therefore the atherosclerotic pattern in the subclavian and innominate arteries may not be explained by differences in these hemodynamic forces.

Identification and characterization of ecologically significant prokaryotes in the sediment of freshwater lakes: molecular and cultivation studies.

The aim of this review is to interpret recent studies in which molecular methods were used to identify and characterize prokaryotes in lake sediments and related habitats. In the first part studies based on the phylogenetic diversity of prokaryotes found in lacustrine habitats are summarized. The application of various cultivation-independent methods for the characterization of distinct groups of sediment bacteria is exemplified with morphologically conspicuous, colorless sulfur bacteria in the second part of this review. Finally, traditional and recently developed methods are described which could be used for linking the function of microbial populations with their identification. The potential of these approaches for the study of lake sediments is discussed in order to give a perspective for future studies in this habitat.

Thyroid hormone-dependent formation of a subcortical band heterotopia (SBH) in the neonatal brain is not exacerbated under conditions of low dietary iron (FeD).

Thyroid hormones (TH) are critical for brain development and insufficiencies can lead to structural abnormalities in specific brain regions. Administration of the goitrogen propylthiouracil (PTU) reduces TH production by inhibiting thyroperoxidase (TPO), an enzyme that oxidizes iodide for the synthesis of TH. TPO activity is iron (Fe)-dependent and dietary iron deficiency (FeD) also reduces circulating levels of TH. We have previously shown that modest degrees of TH insufficiency induced in pregnant rat dams alters the expression of TH-responsive genes in the cortex and hippocampus of the neonate, and results in the formation of a subcortical band heterotopia (SBH) in the corpus callosum (Royland et al., 2008, Bastian et al., 2014, Gilbert et al., 2014). The present experiment investigated if FeD alone was sufficient to induce a SBH or if FeD would augment SBH formation at lower doses of PTU. One set of pregnant rats was administered 0, 1, 3, or 10ppm of PTU via drinking water starting on gestational day (GD) 6. FeD was induced in a 2nd set of dams beginning on GD2. A third set of dams received the FeD diet from GD2 paired with either 1ppm or 3ppm PTU beginning on GD6. All treatments continued until the time of sacrifice. On PN18, one female pup from each litter was sacrificed and the brain examined for SBH. We observed lower maternal, PN2 and PN18 pup serum T4 in response to PTU. FeD reduced serum T4 in pups on PN16, but did not affect serum T4 in dams or PN2 pups. Neither did FeD in combination with PTU alter T4 levels in dams on PN18 or pups on PN2 compared to PTU treatment alone. By PN16, however more severe T4 reductions were observed in pups when FeD was combined with PTU. SBH increased with increasing dosage of PTU, but counter to our hypothesis, no SBH was detected in the offspring of FeD dams. As such, T4 levels in dams and newborn pups rather than older neonates appear to be a better predictor SBH associated with TH insufficiency. These data indirectly support previous work indicating prenatal TH insufficiency but not postnatal TH insufficiency in offspring is required for SBH formation.

Detection and in situ identification of representatives of a widely distributed new bacterial phylum.

16S rRNA gene libraries were prepared by polymerase chain reaction amplification and cloning from soil samples taken periodically from a field with genetically modified plants. Sequence analyses of the cloned rDNAs indicated that 140 of them clustered apart from known bacterial phyla. Based on 31 full sequences a new phylum could be defined. It includes Holophaga foetida, 'Geothrix fermentans' and Acidobacterium capsulatum as the only cultured species so far. Therefore, this line of descent was named the Holophagal Acidobacterium phylum. About 50 published partial sequences of cloned rDNAs retrieved from soil, freshwater sediments or activated sludge from different continents indicate the occurrence of further representatives of this phylum. Two specific hybridization probes were constructed for members of one of four subclusters. A careful data analysis revealed the importance and problems of identifying and dealing with artefacts such as chimeric structure when defining new phylogenetic groups based mainly upon cloned amplified rDNAs. For the first time, the presence of bacterial cells representing this group could be shown in soil, sediment, activated sludge and lake snow by in situ hybridization.

Improved technique for the isolation of magnetotactic spirilla from a freshwater sediment and their phylogenetic characterization.

An improved technique for the isolation of magnetotactic bacteria was used for the axenic cultivation of microaerophilic magnetotactic spirilla. Magnetotactic bacteria were first separated from non-magnetic contaminants by exploiting their active migration along magnetic field lines by a capillary "racetrack" method. The purified magnetic cells were then inoculated into a two-layer isolation medium with opposing oxygen and sulfide gradients. Several strains of magnetotactic spirilla were isolated from a freshwater sediment sample using this method. Based on their morphology, physiology and comparative analysis of almost complete 16S rRNA gene sequences, all newly isolated strains were identified as members of the genus Magnetospirillum. While five of the isolates were closely related to previously described species (> 99% sequence similarity), two isolates appear to represent a third phylogenetic cluster within the genus Magnetospirillum.

Genotypic diversity of Acidovorax strains isolated from activated sludge and description of Acidovorax defluvii sp. nov.

Fluorescence in situ hybridization of activated sludge samples from a municipal wastewater treatment plant using oligonucleotide probes specific for Acidovorax demonstrated that these bacteria are highly abundant in this environment. For the targeted cultivation of representatives belonging to this genus, isolates grown on agar plates after serial dilution were screened by whole-cell hybridization with specific probes. The obtained strains clustered in two phylogenetic groups as determined by 16S rRNA gene sequence analyses. The isolates of one cluster were phylogenetically and genotypically closely related to A. delafieldii. In contrast, the strains of the other cluster were genotypically and phenotypically distinct from the hitherto known Acidovorax species. Therefore, a new species, Acidovorax defluvii sp. nov., was proposed for these strains. The main characteristics of the newly defined species are as follows: Gram-negative, motile or non-motile rods with rounded ends, often with large polyhydroxybutyrate granules. In broth cultures flocs are formed. Test for cytochrome oxidase is positive with all strains. The majority of strains is catalase positive and reduces nitrate. All strains are metabolically inactive against most carbohydrates and organic acids. Fatty acid patterns are typical for the genus Acidovorax. The guanine-plus-cytosine content of DNAs varies between 62 and 64 mol%. The type strain of A. defluvii is BSB411T (DSM 12644). A new 16S rRNA-targeted oligonucleotide probe reacting by in situ hybridization with all known Acidovorax species, including A. defluvii sp. nov., was designed.

Nursing case management: application to neuroscience nursing.

The changing health care environment has challenged nurses to develop creative care delivery systems that provide for quality, comprehensive, cost-effective care in a time of restricted reimbursement and diminishing human and material resources. Nursing case management has been identified as one such approach to health care delivery that has resulted in quality, patient-centered care and improved resource utilization. The case management plan, critical path and discharge planning sheet are primary tools in this care delivery model. Because of the diverse case types and variety of patient care settings, neuroscience nursing is an ideal arena for implementing a nursing case management model of care.

Effect of environmental enrichment devices on behaviors of single- and group-housed squirrel monkeys (Saimiri sciureus).

Squirrel monkeys display an interest in novel places, habituate to new situations, and spend most of their daily activity in the wild in large groups engaging in feeding behaviors over a broad area. Captivity limits these behaviors and consequently may disrupt normal social organizations. In captivity, squirrel monkeys may exhibit stereotypical behaviors that are believed to indicate decreased psychologic well-being. When a monkey's behavior can be made to approach that seen in the wild, and stereotypical behaviors are minimal, it is assumed that psychologic well-being is adequate. Environmental enrichment devices have been used to address the Animal Welfare Act requirement that psychologic well-being of captive nonhuman primates be considered. The purpose of the study reported here was to examine whether various environmental enrichment devices improve the psychologic well-being of captive squirrel monkeys. In the study, we used behavioral observation to quantify the effectiveness of several environmental enrichment devices for reducing stereotypical behaviors in squirrel monkeys housed alone or in groups. Analysis of our results revealed that the environmental enrichment devices did not affect the expression of normal or stereotypical behaviors, but that the type of housing did.

Nursing case management: enhancing interdisciplinary care of the spinal cord injured patient.

Comprehensive care of the person with a spinal cord injury (SCI) requires collaborative, coordinated, interdisciplinary care. It is imperative that the care provided by nurses, therapists, physicians, and ancillary personnel is organized and integrated in a holistic manner if optimal outcomes of rehabilitation are to be achieved. Nursing case management has been identified as an approach to health care delivery that provides quality, patient-centered care. The potential impact of this care delivery model on the health care system for persons with SCI includes quality rehabilitation outcomes, increased patient satisfaction, enhanced interdisciplinary relationships, and improved continuity of care from intensive care to community settings.

Influence of plaque volume on hemodynamic response and stress hormone release in patients undergoing carotid artery stenting.

AIM: Carotid artery stenting (CAS) may cause bradycardia and hypotension due to barostimulation. The impact of periprocedural hypotension on CAS outcome remains controversial. The role of carotid plaque volume and catecholamine hormone release during CAS on hemodynamic changes has not been investigated so far. The aim of this prospective study was to evaluate if carotid artery plaque characteristics are predictive for stress hormone release or for postprocedural hemodynamic instability. METHODS: In 26 patients undergoing CAS, carotid plaque volume and morphology were assessed by two- and three-dimensional (3D)-Duplex sonography prior to the procedure. Arterial plasma adrenaline, noradrenaline and renin concentrations were measured at the time of sheath insertion and 5 minutes after stent placement. ECG, heart rate, and invasive blood pressure were monitored throughout the procedure. RESULTS: CAS caused no significant changes in hormone release, but increasing plaque volume was related to the degree of bradycardia following stent deployment (r=0.57; P=0.01). Plaque size was not associated with postprocedural hypotension. Plaque echogenicity (echolucent, heterogeneous or echogenic) did not correlate with changes in systolic blood pressure, heart rate or catecholamine hormone release. CONCLUSION: CAS caused bradycardia in relation to plaque size, but did not cause catecholamine release which may indicate that the endovascular procedure is not associated with a relevant stress reaction.

Successful reduction of clinical relevant neovascularization with a modified crossectomy combined with a barrier technique after 10-year follow-up.

OBJECTIVE: The aim of this retrospective study was to assess the long-term results of stripping the insufficient great saphenous vein (GSV) with stump coagulation, closure of the cribriform fascia and some additional measures, which will be described in detail. METHODS: Patients treated from 1998 to 1999 for varicose veins had been invited in 2009 for follow-up colour-coded duplex sonography and had been asked to answer a quality-of-life questionnaire. In 2009, the examinations for the study were conducted at a clinic of angiology by an independent and experienced sonographer. RESULTS: From a total of 165 patients, 91 (136 limbs) had been willing to participate in the study. Duplex ultrasound after a mean follow-up of 10.7 years revealed only clinically non-relevant (∅ < 0.3 cm) neovascularizations in 1.5% of all treated legs. No clinical relevant varicosities from the groin had developed. CONCLUSION: The crossectomy combined with stump coagulation and suture of the fossa ovalis, completed with some additional measures, is a successful method to reduce neovascularization and recurrent varicosities, even for redo-crossectomies, without increasing the risk of perioperative complications.

Lack of major gender-related differences in patients undergoing elective endovascular or surgical repair of abdominal aortic aneurysm.

AIM: The aim of this single center retrospective study was to determine gender-related differences in patients undergoing repair of aortic aneurysm. METHODS: A total of 296 consecutive patients with an abdominal aneurysm undergoing elective endovascular or surgical repair was included in the study. Among these, 24 (8.1%) were females and 272 (91.9%) were males. Demographic and clinical characteristics as well as laboratory values in terms of any potential gender-specific differences were compared. RESULTS: Females were significantly older at the time of repair than males. No gender-related differences were found analysing major clinical and laboratory parameters. CONCLUSIONS: The clinical and laboratory profile with which males and females present at the time of elective endovascular or surgical repair for aortic aneurysm is very similar. It does not reveal any potential gender-specific risk constellation. It eventually remains unclear why the prevalence of aortic aneurysm is higher in male than in females.