Preliminary study: treatment with intramuscular interferon beta-1a results in increased levels of IL-12Rβ2+ and decreased levels of IL23R+ CD4+ T - Lymphocytes in multiple sclerosis.

Background: There are a lack of biomarkers which can be used to predict clinical outcomes for multiple sclerosis (MS) patients receiving interferon beta (IFN-β). Thus the objective of this study was to characterize changes in CD4+ T-lymphocyte expression in an unbiased manner following initiation of intramuscular (IM) IFN-β-1a treatment, and then to verify those findings using marker-specific assays.

Methods: Peripheral blood specimens were collected from twenty MS patients before and after treatment with intramuscular (IM) IFN-β-1a and were used for isolation of mononuclear cells (PBMCs).

Genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support the ability to grow in an external pH range from 7.5 to 11.4.

Bacillus pseudofirmus OF4 is an extreme but facultative alkaliphile that grows non-fermentatively in a pH range from 7.5 to above 11.4 and can withstand large sudden increases in external pH.

K⁺ dynamics in ischemic rat brain in vivo by ⁸⁷Rb MRI at 7 T.

The aims of the present study were as follows: (i) to perform the first (87)Rb MRI in live rats with focal ischemic stroke; and (ii) to test the hypothesis that K(+) egress from the brain in this model is quantifiable in individual animals by high-field (7-T) K/Rb substitution MRI. Rats preloaded with dietary Rb(+) (resulting in Rb/(K + Rb) replacement ratios of 0.1-0.

Effects of age and cortical infarction on EEG dynamic changes associated with spike wave discharges in F344 rats.

Rodent models of absence seizures are used to investigate the network properties and regulatory mechanisms of the seizure's generalized spike and wave discharge (SWD). As rats age, SWDs occur more frequently, suggesting aging-related changes in the regulation of the corticothalamic mechanisms generating the SWD. We hypothesized that brain resetting mechanisms - how the brain "resets" itself to a more normal functional state following a transient period of abnormal function, e.

Chaperonin containing T-complex polypeptide (CCT) subunit expression in oral mucosal wounds and fibroblasts.

Mucosal wound healing in adults has been reported to feature diminished scar formation compared to healing skin wounds. We sought to determine if the expression pattern of chaperonin containing T-complex polypeptide (CCT) subunits in mucosal wounds and fibroblasts is different from that observed in skin wounds and fibroblasts. We found that CCT-beta is the only subunit message to be reduced in wounded mucosa versus unwounded control, and this reduction was confirmed at the protein level.

Molecular analysis of coronal perisutural tissues in a craniosynostotic rabbit model using polymerase chain reaction suppression subtractive hybridization.

Background: In the United States, the incidence of craniosynostosis (premature fusion of the sutures of the cranial vault) is one in 2000 to 3000 live births. The condition can cause increased intracranial pressure, severely altered head shape, and mental retardation. The authors have previously described a colony of rabbits with heritable coronal suture synostosis.

Increased expression of Ero1L-alpha in healing fetal wounds.

Background: Adult mammalian tissues heal injury to the skin with formation of scar; this process quickly seals an injured area, however, excessive scar formation can become a source of persistent pathology, interfering with multiple vital functions. In contrast, mammalian fetal tissue can heal without scar formation. We previously sought to model scarless healing in a rabbit fetal skin wound and identified gene products differentially expressed during fetal wound healing through PCR suppression subtractive hybridization (PCR SSH).

Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's-derived fibroblasts.

Background: Myofibroblasts, a derived subset of fibroblasts especially important in scar formation and wound contraction, have been found at elevated levels in affected Dupuytren's tissues. Transformation of fibroblasts to myofibroblasts is characterized by expression of alpha- smooth muscle actin (α-SMA) and increased production of extracellular matrix (ECM) components, both events of relevance to connective tissue remodeling. We propose that increasing the activation of the cyclic AMP (cAMP)/protein kinase A signaling pathway will inhibit transforming growth factor-beta1 (TGF-β1)-induced ECM synthesis and myofibroblast formation and may provide a means to blunt fibrosis.

Comparative supragenomic analyses among the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae using a modification of the finite supragenome model.

Background: Staphylococcus aureus is associated with a spectrum of symbiotic relationships with its human host from carriage to sepsis and is frequently associated with nosocomial and community-acquired infections, thus the differential gene content among strains is of interest.

Results: We sequenced three clinical strains and combined these data with 13 publically available human isolates and one bovine strain for comparative genomic analyses. All genomes were annotated using RAST, and then their gene similarities and differences were delineated.

Alterations of GABA(A) and glutamate receptor subunits and heat shock protein in rat hippocampus following traumatic brain injury and in posttraumatic epilepsy.

Traumatic brain injury (TBI) can result in the development of posttraumatic epilepsy (PTE). Recently, we reported differential alterations in tonic and phasic GABA(A) receptor (GABA(A)R) currents in hippocampal dentate granule cells 90 days after controlled cortical impact (CCI) (Mtchedlishvili et al., 2010).

Characterization of a mixed MRSA/MRSE biofilm in an explanted total ankle arthroplasty.

Bacterial biofilms have been observed in many prosthesis-related infections, and this mode of growth renders the infection both difficult to treat and especially difficult to detect and diagnose using standard culture methods. We (1) tested a novel coupled PCR-mass spectrometric (PCR-MS) assay (the Ibis T5000) on an ankle arthroplasty that was culture negative on preoperative aspiration and then (2) confirmed that the Ibis assay had in fact detected a viable multispecies biofilm by further micrographic and molecular examinations, including confocal microscopy using Live/Dead stain, bacterial FISH, and reverse-transcriptase-PCR (RT-PCR) assay for bacterial mRNA. The Ibis technology detected Staphylococcus aureus, Staphylococcus epidermidis, and the methicillin resistance gene mecA in soft tissues associated with the explanted hardware.

Adenoid reservoir for pathogenic biofilm bacteria.

Biofilms of pathogenic bacteria are present on the middle ear mucosa of children with chronic otitis media (COM) and may contribute to the persistence of pathogens and the recalcitrance of COM to antibiotic treatment. Controlled studies indicate that adenoidectomy is effective in the treatment of COM, suggesting that the adenoids may act as a reservoir for COM pathogens. To investigate the bacterial community in the adenoid, samples were obtained from 35 children undergoing adenoidectomy for chronic OM or obstructive sleep apnea.

Cellular and Molecular Characteristics of Scarless versus Fibrotic Wound Healing.

The purpose of this paper is to compare and contrast the discrete biology differentiating fetal wound repair from its adult counterpart. Integumentary wound healing in mammalian fetuses is essentially different from wound healing in adult skin. Adult (postnatal) skin wound healing is a complex and well-orchestrated process spurred by attendant inflammation that leads to wound closure with scar formation.

New methods for the detection of orthopedic and other biofilm infections.

The detection and identification of bacteria present in natural and industrial ecosystems is now entirely based on molecular systems that detect microbial RNA or DNA. Culture methods were abandoned, in the 1980s, because direct observations showed that <1% of the bacteria in these systems grew on laboratory media. Culture methods comprise the backbone of the Food and Drug Administration-approved diagnostic systems used in hospital laboratories, with some molecular methods being approved for the detection of specific pathogens that are difficult to grow in vitro.

Multiple displacement amplification as an adjunct to PCR-based detection of Staphylococcus aureus in synovial fluid.

Background: Detection of bacterial nucleic acids in synovial fluid following total joint arthroplasty with suspected infection can be difficult; among other technical challenges, inhibitors in the specimens require extensive sample preparation and can diminish assay sensitivity even using polymerase chain reaction (PCR)-based methods. To address this problem a simple protocol for prior use of multiple displacement amplification (MDA) as an adjunct to PCR was established and tested on both purified S. aureus DNA as well as on clinical samples known to contain S.

α-Galactosidase A expressed in the salivary glands partially corrects organ biochemical deficits in the fabry mouse through endocrine trafficking.

Fabry disease is caused by an X-linked deficiency of the lysosomal enzyme α-galactosidase A (GLA) and has been treated successfully with enzyme replacement therapy (ERT). Gene therapy has been proposed as an alternative to ERT due to the presumed advantages of continuous, endogenous production of the therapeutic enzyme. GLA production in the liver and its therapeutic efficacy in the Fabry mouse have been demonstrated previously with various viral vector systems.

Direct demonstration of Staphylococcus biofilm in an external ventricular drain in a patient with a history of recurrent ventriculoperitoneal shunt failure.

External ventricular drains (EVD) are associated with a high infection rate. Early detection of infection is frequently problematic due to a lack of clinical signs and the time period required for culturing. Bacterial biofilms have been suggested to play an important role in the infection of EVD, but direct evidence is as yet lacking.

The distributed genome hypothesis as a rubric for understanding evolution in situ during chronic bacterial biofilm infectious processes.

Most chronic infectious disease processes associated with bacteria are characterized by the formation of a biofilm that provides for bacterial attachment to the host tissue or the implanted medical device. The biofilm protects the bacteria from the host's adaptive immune response as well as predation by phagocytic cells. However, the most insidious aspect of biofilm biology from the host's point of view is that the biofilm provides an ideal setting for bacterial horizontal gene transfer (HGT).

Bacterial biofilm on monofilament suture and porcine xenograft after inguinal herniorrhaphy.

Bacterial biofilms have been implicated in multiple clinical scenarios involving infection of implanted foreign bodies, but have been little studied after hernia repair. We now report a case of revision inguinal herniorrhaphy complicated by chronic pain at the operated site without any external indication of infection. Computed tomographic imaging revealed a contrast-enhancing process in the left groin.

Ultrasound-assisted non-viral gene transfer to the salivary glands.

We report a non-viral gene transfer method using ultrasound induced microbubble destruction to allow the uptake of plasmid gene transfer vectors to the cells of the mouse salivary gland. The Luciferase (Luc) reporter gene, driven by a cytomegalovirus (CMV) promoter, was delivered unilaterally to the submandibular salivary gland via retroductal cannulation and Luc expression was monitored with in vivo imaging. The CMV-Luc plasmid was delivered to the salivary gland in a carrier solution containing microbubbles composed of lipid-encased perfluoropropane gas, with two different concentrations of microbubbles used (100 and 15% volume/volume).

Perineal hernia repair with acellular dermal graft and suture anchor fixation.

Perineal hernia is an infrequent complication of abdominoperineal resection, but can be problematic. Multiple surgical approaches to the repair of perineal hernia have been described, including abdominal, perineal, and combined methods; most feature the use of a prosthetic mesh. We report a case wherein a large perineal hernia was reduced via an abdominal approach, and then repaired by the placement of an acellular dermal graft (DermaMatrix) fixated anteriorly directly to the pubis with Mitek suture anchors.

Assessment of a scalp EEG-based automated seizure detection system.

Objective: The purpose of this study was to evaluate and validate an offline, automated scalp EEG-based seizure detection system and to compare its performance to commercially available seizure detection software.

Methods: The test seizure detection system, IdentEvent™, was developed to enhance the efficiency of post-hoc long-term EEG review in epilepsy monitoring units. It translates multi-channel scalp EEG signals into multiple EEG descriptors and recognizes ictal EEG patterns.

Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is a specific regulator of fibroblast motility and contractility.

Integumentary wounds in mammalian fetuses heal without scar; this scarless wound healing is intrinsic to fetal tissues and is notable for absence of the contraction seen in postnatal (adult) wounds. The precise molecular signals determining the scarless phenotype remain unclear. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is specifically reduced in healing fetal wounds in a rabbit model.