Punicalagin attenuates isoproterenol-induced myocardial infarction through nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1-mediated inhibition of inflammation and cardiac stress markers in experimental animal models.

Myocardial infarction (MI) is a significant global health issue and the leading cause of death. Myocardial infarction (MI) is characterized by events such as damage to heart cells and stress generated by inflammation. Punicalagin (PCN), a naturally occurring bioactive compound found in pomegranates, exhibits a diverse array of pharmacological effects against many disorders. This study aimed to assess the preventive impact of PCN, with its potential anti-inflammatory and antioxidant properties, on myocardial injury caused by isoproterenol (ISO) in rats and elucidate the possible underlying mechanisms. Experimental rats were randomly categorized into four groups: control group (fed a regular diet for 15 days), PCN group (orally administered PCN at 50 mg/kg body weight (b.w.) for 15 days), ISO group (subcutaneously administered ISO (85 mg/kg b.w.) on days 14 and 15 to induce MI), and PCN+ISO group (orally preadministered PCN (50 mg/kg b.w.) for 15 days and administered ISO (85 mg/kg b.w.) on days 14 and 15). The rat cardiac tissue was then investigated for cardiac marker, oxidative stress marker, and inflammatory marker expression levels. PCN prevented ISO-induced myocardial injury, suppressing the levels of creatine kinase-myocardial band, C-reactive protein, homocysteine, cardiac troponin T, and cardiac troponin I in the rats. Moreover, PCN treatment reversed (P<0.01) the ISO-induced increase in blood pressure, attenuated lipid peroxidation markers, and depleted both enzymatic and nonenzymatic markers in the rats. Additionally, PCN inhibited (P<0.01) ISO-induced overexpression of oxidative stress markers (p-38, p-c-Jun N-terminal kinase, and p-extracellular signal-regulated kinase 1), inflammatory markers (nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-6), and matrix metalloproteinases and decreased the levels (P<0.01) of apoptosis proteins in the rats. Nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1 (Nrf2/Sirt1) is a major cellular defense protein that regulates and scavenges oxidative toxic substances through apoptosis. Therefore, overexpression of Nrf2/Sirt1 to inhibit inflammation and oxidative stress is considered a novel target for preventing MI. PCN also significantly enhanced the expression of Nrf2/Sirt1 in ISO-induced rats. Histopathological analyses of cardiac tissue revealed that PCN treatment exhibited a protective effect on the heart tissue, mitigating damage. These findings show that by activating the Nrf2/Sirt1 pathway, PCN regulates oxidative stress, inflammation, and apoptosis, hence providing protection against ISO-induced myocardial ischemia.

Laparoscopic preperitoneal repair for primary falciform ligament herniation.

Epigastric hernia involving the falciform ligament is exceptionally rare. Most reported cases are incisional hernia secondary to prior abdominal surgery. We report a case of primary falciform ligament herniation into the epigastric region repaired by the laparoscopic preperitoneal approach. In this case, an accompanying vessel along the herniated falciform ligament was identified. This finding provides a basis for the hypothesis of a perforating vessel piercing the linea alba and thereby creating a weak point for hernia protrusion (Moschowitz theory). The patient had an uneventful recovery and was discharged home on the postoperative day two. A laparoscopic preperitoneal approach is feasible for the repair of primary falciform ligament herniation. The magnified endoscopic view enables surgeons to achieve definite repair without missing occult defects.

Imaging Informatics Fellowship Curriculum: a Survey to Identify Core Topics and Potential Inter-Program Areas of Collaboration.

New consumer technologies and interoperability standards have dated the first standardized curriculum for imaging informatics fellowships suggested by the Society for Computer Applications in Radiology (SCAR) in 2004 (Journal of digital imaging 17(4):244-248, 2004). Last year, analysis from this institution characterized current state fellowship graduation requirements and broad curriculum topics for the first time in over a decade (SIIM Strategic Plan 2017-2020). However, an updated "core" curriculum has not yet been developed. Using the recent current state analysis as a baseline, we aimed to perform a focused assessment and propose that this would work towards an updated consensus "core" curriculum as outlined by the Society for Imaging Informatics in Medicine (SIIM, previously SCAR) strategic plan. A secondary aim was to identify individual program strengths and weaknesses to foster inter-program collaboration. Using sub-topics from the National Imaging Informatics Curriculum (NIIC), a week-long introductory course for residents, we expanded the original 29 broad curriculum categories identified in last year's current state analysis into 114 sub-topics. We surveyed imaging informatics fellowship directors to identify sub-topic prioritization on a 5-item Likert scale, teaching methods for each sub-topic, cross-departmental partnerships, and individual program strengths and weaknesses. Only 8% of sub-topics (10/114) received a "definitely" rating with 100% agreement while the majority of sub-topics 77% (88/114) had mixed grading defined by two or fewer "definitely" ratings. These sub-topics mapped to only 4 of the original 29 broad fellowship curriculum categories including Standards, Programming/Development/Software, Infrastructure, and PACS/RIS/Reporting. Our plan is to use consensus topics to build a "core" informatics fellowship curriculum and initiate discussion surrounding mixed grading topics. Knowledge of individual program strengths and weaknesses can be used to foster inter-program collaboration.

A Survey of Imaging Informatics Fellowships and Their Curricula: Current State Assessment.

In a 2016 survey of imaging informatics ("II") fellowship graduates, the surveyed fellowship graduates expressed the "opinion that II fellowships needed further formalization and standardization" Liao et al. (J Digit Imaging, 2016). This, coupled with the fact that the original published "standardized" curriculum is about 15 years out of date in our rapidly changing systems, suggests an opportunity for curriculum improvement. Before agreeing on improved structural and content suggestions for fellowships, we completed a current-state assessment of how each fellowship organizes its education and what requirements each have for fellowship completion. In this work, we aimed to collect existing information about imaging informatics fellowship curricula by contacting institutions across the country. A survey was completed by phone with the fellowship directors of existing imaging informatics fellowships across the country. Additionally, we collected existing documentation that outlines the curricula currently in use at institutions. We reviewed both the interview responses and documentation to assess overlapping trends and institutional differences in curriculum structure and content. All fellowships had suggested reading lists, didactic lectures, and a required project for each fellow. There were required practicum activities or teaching experience each in two fellowships, and one fellowship had a mandatory certification requirement for graduation. Curriculum topics in Technical Informatics or Business and Management were covered by a majority of institutions, while Quality and Safety and Research topics had inconsistent coverage across fellowships. Our plan is to reengage II fellowship directors to develop a core curriculum, which is part of the Society of Imaging Informatics in Medicine strategic plan.

Detection of the Stellate and Thoracic Sympathetic Chain Ganglia with High-Resolution 3D-CISS MR Imaging.

BACKGROUND AND PURPOSE: Despite the importance of the sympathetic nervous system in homeostasis and its putative role in various disease states, little is known regarding our ability to image the sympathetic chain and sympathetic chain ganglia, perhaps owing to their small size. In this retrospective study, we sought to evaluate the normal anatomy of the sympathetic chain ganglia and assess the detectability of the sympathetic chain and sympathetic chain ganglia on high-resolution 3D-CISS images. MATERIALS AND METHODS: This study included 29 patients who underwent 3D-CISS MR imaging of the thoracic spine for reasons unrelated to abnormalities of the sympathetic nervous system. Patients with a prior spinal operation or visible spinal pathology were excluded. The sympathetic chain ganglia were evaluated using noncontrast 3D-CISS MR imaging. Statistical analyses included t tests and measures of central tendency. The Cohen κ statistic was calculated to evaluate interrater reliability. RESULTS: The stellate ganglion and thoracic chain ganglia were identified in all subjects except at the T10-T11 and T11-T12 levels. The stellate ganglion was found inferomedial to the subclavian artery and anterior and inferior to the transverse process of C7 in all subjects. Thoracic sympathetic chain ganglia were identified ventral to the costovertebral junction in all subjects from T2 to T10. There was strong interobserver agreement for the detection of the sympathetic chain ganglia with κ > 0.80. The size, shape, and location of these structures corresponded with gross anatomic and surgical observations. CONCLUSIONS: The thoracic sympathetic chain ganglia can be identified on precontrast 3D-CISS MR imaging. This technique may aid in the initial evaluation of stellate ganglion and/or sympathetic chain ganglia size and signal change for comparison in future studies.

A systematic review of ultrasound imaging as a tool for evaluating haemophilic arthropathy in children and adults.

The purpose of this study was to semi-quantitatively assess the evidence on the value of ultrasound (US) for assessment of haemophilic arthropathy (HA) in children and adults based on the following questions: (1) Does early diagnosis of pathological findings, using available US techniques, impact the functional status of the joint? (2) Do current available US techniques have the ability to accurately detect pathological changes in target joints in haemophilic patients? (3) Does treatment (prophylaxis) improve US evidence of haemophilic arthropathy in children and adults? (4) Is there any association between various US scoring systems and other clinical/radiological constructs? Of the 6880 citations identified searching databases such as MEDLINE, Embase, CENTRAL and Web of Science, 20 articles investigating either the diagnostic accuracy of US and/or US scanning protocols and scoring systems for assessment of HA met the inclusion criteria for the study. Of these, 14 articles evaluating the diagnostic accuracy of US were assessed by two independent reviewers for reporting quality using the Standards for Reporting of Diagnostic Accuracy (STARD) tool and for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Using STARD, 1/14 studies (7%) was scored as of high reporting quality and 8/14 (57%), of moderate quality. Assessment with QUADAS-2 reported 2/14 (14%) studies as having high methodological quality and 6/14 (43%) as having moderate quality. There is fair evidence (Grade B) to recommend US as an accurate technique for early diagnosis of HA, to demonstrate that US scores correlate with clinical/US constructs and to prove an association between US findings and functional status of the joint. However, there is insufficient evidence (Grade I) to conclude that US-detectable findings in HA are sensitive to changes in therapy.

Dilute versus concentrated vasopressin administration during laparoscopic myomectomy: a randomised controlled trial.

OBJECTIVE: To determine if higher-volume, fixed-dose administration of vasopressin further reduces blood loss at the time of minimally invasive myomectomy. DESIGN: Randomised multicentre clinical trial. SETTING: Tertiary-care academic centres in the USA. POPULATION: Women undergoing conventional laparoscopic or robot-assisted laparoscopic myomectomy. METHODS: All participants received the same 10-unit (U) dose of vasopressin, but were randomly assigned to one of two groups: (i) received 200 ml of diluted vasopressin solution (20 U in 400 ml normal saline), and (ii) received 30 ml of concentrated vasopressin solution (20 U in 60 ml normal saline). MAIN OUTCOME MEASURES: The primary study outcome was estimated blood loss; the study was powered to detect a 100-ml difference. RESULTS: A total of 152 women were randomised; 76 patients in each group. Baseline demographics were similar between groups. The primary outcome of intraoperative blood loss was not significantly different, as measured by three parameters: surgeon estimate (mean estimated blood loss 178 ± 265 ml and 198 ± 232 ml, dilute and concentrated groups respectively, P = 0.65), suction canister-calculated blood loss, or change in haematocrit levels. There were no vasopressin-related adverse events. CONCLUSION: Both dilute and concentrated vasopressin solutions that use the same drug dosing demonstrate comparable safety and tolerability when administered for minimally invasive myomectomy; however, higher volume administration of vasopressin does not reduce blood loss. TWEETABLE ABSTRACT: This randomised trial failed to show benefit of high-volume dilute vasopression.

Limited Dorsal Myeloschisis and Congenital Dermal Sinus: Comparison of Clinical and MR Imaging Features.

BACKGROUND AND PURPOSE: While limited dorsal myeloschisis is a distinctive form of spinal dysraphism, it may be confused with congenital dermal sinus. The aim of this study was to describe clinical and MR imaging findings of limited dorsal myeloschisis that can distinguish it from congenital dermal sinus. MATERIALS AND METHODS: We retrospectively reviewed the clinical and MR imaging findings of 12 patients with limited dorsal myeloschisis and 10 patients with congenital dermal sinus. Skin abnormalities, neurologic deficits, and infectious complication were evaluated on the basis of clinical information. We evaluated the following MR imaging features: visibility of the tract along the intrathecal course, attachment site of the tract, level of the conus medullaris, shape of the spinal cord, and presence of intradural lesions such as dermoid/epidermoid tumors. RESULTS: A crater covered with pale epithelium was the most common skin lesion in limited dorsal myeloschisis (10/12, 83%). Infectious complications were common in congenital dermal sinus (6/10, 60%), whereas none were found in limited dorsal myeloschisis (P = .003). The following MR imaging findings were significantly different between the 2 groups (P < .05): 1) higher visibility of the intrathecal tract in limited dorsal myeloschisis (10/12, 83%) versus in congenital dermal sinus (1/10, 10%), 2) the tract attached to the cord in limited dorsal myeloschisis (12/12, 100%) versus various tract attachments in congenital dermal sinus, 3) dorsal tenting of the cord in limited dorsal myeloschisis (10/12, 83%) versus in congenital dermal sinus (1/10, 10%), and 4) the presence of dermoid/epidermoid tumors in congenital dermal sinus (6/10, 60%) versus none in limited dorsal myeloschisis. CONCLUSIONS: Limited dorsal myeloschisis has distinct MR imaging features: a visible intrathecal tract with dorsal tenting of the cord at the tract-cord union. Limited dorsal myeloschisis was not associated with infection and dermoid/epidermoid tumors.

Longitudinal assessment of bone loss using quantitative ultrasound in a blood-induced arthritis rabbit model.

INTRODUCTION: Osteoporosis is common in haemophilic arthropathy. Quantitative ultrasound (QUS) can be a suitable alternative for dual-energy x-ray absorptiometry for diagnosing osteoporosis in haemophiliacs due to its lack of ionizing radiation, and ease to use. AIM: We investigated the intra- and inter-operator reliability of QUS, its responsiveness to bone growth, its ability to differentiate bone adjacent to blood-injected vs. control joints, and the effect of soft tissues on the speed of sound (SOS) QUS values in a juvenile white New Zealand rabbit model of blood-induced arthritis. METHODS: Eight of 16 rabbits were injected with autologous blood (0.1 mL kg(-1) ) 8 times over a 17-week period, the remaining eight rabbits served as controls. SOS was measured at baseline, weeks 8 and 17 in vivo and after the bones were excised on week 17. RESULTS: Intra- and inter-operator coefficients of variation for QUS data were <5% and intraclass correlation coefficients were >60% for 22/27 (81.5%) of bones assessed. The level of interval increase in SOS values from baseline to week 17 was significantly different in tibiae of injected, contralateral to injected and non-injected knee groups by anova (P = 0.01). In vivo (mean ± SD, 4147.17 ± 96.27 m s(-1) ) and postmortem (4457.85 ± 104.00 m s(-1) ) measurements on week 17 differed (P < 0.01) indicating an effect of soft tissues on SOS. CONCLUSION: In conclusion, QUS' acceptable reliability, its responsiveness to growth-related changes and its ability to discriminate injected and non-injected joints make this technique a plausible candidate as a diagnostic tool for osteoporosis in the paediatric haemophilic population if these results are confirmed upon animal-human translation.

Clinically applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem gliomas.

Pediatric brainstem glioma is an incurable malignancy because of its inoperability. As a result of their extensive tropism toward cancer and the possibility of autologous transplantation, human adipose-derived mesenchymal stem cells (hAT-MSC) are attractive vehicles to deliver therapeutic genes to brainstem gliomas. In this study, in a good manufacturing practice (GMP) facility, we established clinically applicable hAT-MSCs expressing therapeutic genes and investigated their therapeutic efficacy against brainstem glioma in mice. For feasible clinical applications, (1) primary hAT-MSCs were cultured from human subcutaneous fat to make autologous transplantation possible, (2) hAT-MSCs were genetically engineered to express carboxyl esterase (CE) and (3) a secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) expression vector for synergistic effects was delivered by a gene transfer technology that did not result in genomic integration of the vector. (4) Human CE and sTRAIL sequences were utilized to avoid immunological side effects. The hAT-MSCs expressing CE±sTRAIL showed significant therapeutic effects against brainstem gliomas in vitro and in vivo. However, the simultaneous expression of CE and sTRAIL had no synergistic effects in vivo. The results indicate that non-viral transient single sTRAIL gene transfer to autologous hAT-MSCs is a clinically applicable stem cell-based gene therapy for brainstem gliomas in terms of therapeutic effects and safety.

Blood trace minerals concentrations and oxidative stress in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased oxidative stress. Certain essential trace minerals have shown to play an important role in the maintenance of redox homeostasis. We determined the concentrations of trace minerals in OSA patients and assessed their relationships to OSA severity as indicated by the apnea/ hypopnea index (AHI). METHODS: We enrolled 44 patients with newly diagnosed mild to moderate OSA and 20 without OSA. The following parameters were measured: polysomnographic values of nocturnal sleep; plasma trace minerals zinc (Zn), copper (Cu), iron (Fe), and erythrocyte selenium (Se); oxidative stress status; and plasma high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). RESULTS: Compared to controls matched for age, gender, and body mass index, OSA patients had lower concentrations of plasma Zn and erythrocyte Se and higher plasma concentrations of Cu and Fe. OSA patients had significantly higher plasma concentrations of hs-CRP, TNF-α, and malondialdehyde (MDA), and lower erythrocyte antioxidant enzyme glutathione peroxidase (GPx) and superoxide dismutase activities. Significant differences in all the above parameters were also found in patients with moderate OSA compared to those with mild OSA. Furthermore, AHI values correlated significantly with neck circumference, GPx activity, and MDA, hs-CRP, and TNF-α concentrations in OSA patients. AHI values were also negatively associated with concentrations of plasma Zn and erythrocyte Se, but were positively linked to plasma concentrations of Fe and Cu. CONCLUSIONS: Abnormal concentrations of these trace minerals may reflect oxidative damage and inflammatory response, thus increasing the severity of OSA.

Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats.

Infection during early neonatal period has been shown to cause lasting neurological disabilities and is associated with the subsequent impairment in development of learning and memory ability and anxiety-related behavior in adults. We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in cognitive deficits in juvenile rats (P21); thus, the goal of the present study was to determine whether neonatal LPS exposure has long-lasting effects in adult rats. After an LPS (1mg/kg) intracerebral (i.c.) injection in postnatal day 5 (P5) Sprague-Dawley female rat pups, neurobehavioral tests were carried out on P21 and P22, P49 and P50 or P70 and P71 and brain injury was examined at 66days after LPS injection (P71). Our data indicate that neonatal LPS exposure resulted in learning deficits in the passive avoidance task, less anxiety-like (anxiolytic-like) responses in the elevated plus-maze task, reductions in the hippocampal volume and the number of neuron-specific nuclear protein (NeuN)+ cells, as well as axonal injury in the CA1 region of the middle dorsal hippocampus in P71 rats. Neonatal LPS exposure also resulted in sustained inflammatory responses in the P71 rat hippocampus, as indicated by an increased number of activated microglia and elevation of interleukin-1ß content in the rat hippocampus. This study reveals that neonatal LPS exposure causes persistent injuries to the hippocampus and results in long-lasting learning disabilities, and these effects are related to the chronic inflammation in the rat hippocampus.

Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal stem cells of women.

OBJECTIVE: To determine whether estrogen regulates mesenchymal stem cell (MSC) activity in bone marrow from osteoporotic postmenopausal women. METHODS: MSCs were collected from bone marrows which were aspirated simultaneously during iliac bone graft procedures in spine fusion surgery in osteoporotic postmenopausal women. We investigated proliferation, differentiation, osteogenic activity, and estrogen receptor (ER) α and ß mRNA expression of primary culture MSCs isolated from four osteoporotic postmenopausal women, treated in vitro with or without 17ß-estradiol. The expression of alkaline phosphatase (ALP), osteocalcin, interleukin-6, ERα and ERß mRNA was evaluated. RESULTS: The expression of ALP and osteocalcin mRNA was detected during the cultures of MSCs and was observed to increase up to day 20. As compared with MSCs not treated with estradiol, a significant increase in DNA content, ERα mRNA, and ALP mRNA expression was observed in cultures with estradiol. The mRNA expression of osteocalcin and interleukin-6 was significantly lower in MSCs treated with estradiol than those without estradiol. There was no significant difference in the mRNA expression of ERß between MSCs cultured with and without estradiol. CONCLUSIONS: In the proper environment, MSCs from osteoporotic women can differentiate into osteoblasts and estrogen enhances the osteogenic activity possibly via ERα activity.

Elevated plasma high-mobility group box 1 protein is a potential marker for neuromyelitis optica.

High-mobility group box 1 protein (HMGB1) has cytokine activities and mediates systemic inflammation as well as immune responses. The aim of this study was to determine if plasma HMGB1 level can be used as a marker for neuromyelitis optica (NMO) and to differentiate NMO from multiple sclerosis (MS). We measured plasma levels of HMGB1, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin 17 (IL-17) in 29 patients with NMO and 20 patients with MS at enrollment and at 2years follow-up (at the time of definitive diagnosis) by enzyme-linked immunosorbent assay. Plasma HMGB1 level was significantly greater in the NMO group compared to the MS group (P<0.001). Plasma levels of TNF-α, IFN-γ, and IL-17 were significantly greater in the NMO group compared to the MS group, and HMGB1 level was positively correlated with TNF-α, IFN-γ, and IL-17 levels. Univariate logistic regression analysis showed a significant association of HMGB1 level, and IFN-γ level with NMO diagnosis. Although this study included a limited sample size, we attempted to determine an optimized cutoff point for HMGB1 (≥2 ng/ml), which provided 89.7% sensitivity and 95.0% specificity for the diagnosis of NMO. These results indicate that plasma HMGB1 level might serve as a surrogate marker for NMO disease activity and aid in the differentiation of NMO from MS at the early disease stage.

Early origins of heart disease: low birth weight and determinants of cardiomyocyte endowment.

1. World-wide epidemiological and experimental animal studies demonstrate that adversity in fetal life, resulting in intrauterine growth restriction, programmes the offspring for a greater susceptibility to ischaemic heart disease and heart failure in adult life. 2. After cardiogenesis, cardiomyocyte endowment is determined by a range of hormones and signalling pathways that regulate cardiomyocyte proliferation, apoptosis and the timing of multinucleation/terminal differentiation. 3. The small fetus may have reduced cardiomyocyte endowment owing to the impact of a suboptimal intrauterine environment on the signalling pathways that regulate cardiomyocyte proliferation, apoptosis and the timing of terminal differentiation.

Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase.

The prognosis of medulloblastoma has improved significantly because of advances in multi-modal treatments; however, metastasis remains one of the prognostic factors for a poor outcome and is usually associated with tumor recurrence. We evaluated the migratory potential and therapeutic efficacy of genetically engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN-38). To simulate clinical metastatic medulloblastomas, we implanted human medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE cells migrated to the subdural medulloblastoma site and a small number of F3.rCE cells were found in the lungs, pancreas, kidney and liver. Animals that received F3.rCE cells in combination with prodrug CPT-11 survived significantly longer (median survival: 142 days) than control mice that received F3.rCE cells only (median survival: 80 days, P<0.001) or CPT-11 only (median survival: 118 days, P<0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural medulloblastomas and demonstrate therapeutic efficacy. Our study provides data that supports further investigation of stem-cell-based gene therapy against metastatic medulloblastomas.

Penaeus monodon TATA box-binding protein interacts with the white spot syndrome virus transactivator IE1 and promotes its transcriptional activity.

We show here that the white spot syndrome virus (WSSV) immediate-early protein IE1 interacts with the Penaeus monodon TATA box-binding protein (PmTBP) and that this protein-protein interaction occurs in the absence of any other viral or cellular proteins or nucleic acids, both in vitro and in vivo. Mapping studies using enhanced green fluorescent protein (EGFP) fusion proteins containing truncations of IE1 and PmTBP delimited the interacting regions to amino acids (aa) 81 to 180 in IE1 and, except for aa 171 to 230, to aa 111 to 300 in PmTBP. A WSSV IE1 transactivation assay showed that large quantities (>800 ng) of the GAL4-IE1 plasmid caused "squelching" of the GAL4-IE1 activity and that this squelching effect was alleviated by the overexpression of PmTBP. Gene silencing of WSSV ie1 and PmTBP by pretreatment with double-stranded RNAs (dsRNAs) prior to WSSV challenge showed that the expression of these two target genes was specifically inhibited by their corresponding dsRNAs 72 and 96 h after dsRNA treatment. dsRNA silencing of ie1 and PmTBP expression also significantly reduced WSSV replication and the expression of the viral early gene dnapol (DNA polymerase gene). These results suggest that WSSV IE1 and PmTBP work cooperatively with each other during transcription initiation and, furthermore, that PmTBP is an important target for WSSV IE1's transactivation activity that can enhance viral gene expression and help in virus replication.

Penaeus monodon Dscam (PmDscam) has a highly diverse cytoplasmic tail and is the first membrane-bound shrimp Dscam to be reported.

Down syndrome cell adhesion molecule (Dscam) seems likely to play a key role in the "alternative adaptive immunity" that has been reported in invertebrates. Dscam consists of a cytoplasmic tail that is involved in signal transduction and a hypervariable extracellular region that might use a pathogen recognition mechanism similar to that used by the vertebrate antibodies. In our previous paper, we isolated a unique tail-less form of Dscam from Litopenaeus vannamei. In this study, we report the first membrane-bound form of shrimp Dscam: PmDscam was isolated from Penaeus monodon, and it occurred in both membrane-bound and tail-less forms. Phylogenetic analysis showed that while the crustacean Dscams from shrimp and water flea did not share a single subclade, they were distinct from the invertebrate Dscam-like molecules and from the insecta Dscams. In the extracellular region, the variable regions of PmDscam were located in N-terminal Ig2, N-terminal Ig3 and the entire Ig7 domain. The PmDscam extracellular variants and transmembrane domain variants were produced by mutually exclusive alternative splicing events. The cytoplasmic tail variants were produced by exon inclusion/exclusion. Based on the genomic organization of Daphnia Dscam's cytoplasmic tail, we propose a model of how the shrimp Dscam genomic locus might use Type III polyadenylation to generate both the tail-less and membrane-bound forms.

High-resolution MR neurography of diffuse peripheral nerve lesions.

High-resolution MR imaging of peripheral nerves is becoming more common and practical with the increasing availability of 3T magnets. There are multiple reports of MR imaging of peripheral nerves in compression and entrapment neuropathies. However, there is a relative paucity of literature on MRN appearance of diffuse peripheral nerve lesions. We attempted to highlight the salient imaging features of myriad diffuse peripheral nerve disorders and imaging techniques for MRN. Using clinical and pathologically proved relevant examples, we present the MRN appearance of various types of diffuse peripheral nerve lesions, such as traumatic, inflammatory, infectious, hereditary, radiation-induced, neoplastic, and tumor variants.