Amino Acid Tracer PET MRI in Glioma Management: What a Neuroradiologist Needs to Know.

PET with amino acid tracers provides additional insight beyond MR imaging into the biology of gliomas that can be used for initial diagnosis, delineation of tumor margins, planning of surgical and radiation therapy, assessment of residual tumor, and evaluation of posttreatment response. Hybrid PET MR imaging allows the simultaneous acquisition of various PET and MR imaging parameters in a single investigation with reduced scanning time and improved anatomic localization. This review aimed to provide neuroradiologists with a concise overview of the various amino acid tracers and a practical understanding of the clinical applications of amino acid PET MR imaging in glioma management. Future perspectives in newer advances, novel radiotracers, radiomics, and cost-effectiveness are also outlined.

A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.

The intersection of gender and drug use-related stigma: A mixed methods systematic review and synthesis of the literature.

BACKGROUND: Substance use-related stigma is a significant barrier to care among persons who use drugs (PWUD). Less is known regarding how intersectional identities, like gender, shape experiences of substance use-related stigma. We sought to answer the following question: Do men or women PWUD experience more drug use stigma? METHODS: Data were drawn from a systematic review of the global, peer-reviewed scientific literature on substance use-related stigma conducted through 2017 and guided by the Stigma and Substance Use Process Model and PRISMA guidelines. Articles were included in the present analysis if they either qualitatively illustrated themes related to the gendered nature of drug use-related stigma, or quantitatively tested the moderating effect of gender on drug use-related stigma. RESULTS: Of the 75 studies included, 40 (53 %) were quantitative and 35 (47 %) were qualitative. Of the quantitative articles, 22 (55 %) found no association between gender and drug use-related stigma, 4 (10 %) identified women who use drugs (WWUD) were more stigmatized, and 2 (5 %) determined men who use drugs (MWUD) were more stigmatized. In contrast, nearly all (34; 97 %) of the qualitative articles demonstrated WWUD experienced greater levels of drug use-related stigma. CONCLUSION: The quantitative literature is equivocal regarding the influence of gender on drug use-related stigma, but the qualitative literature more clearly demonstrates WWUD experience greater levels of stigma. The use of validated drug use-related stigma measures and the tailoring of stigma scales to WWUD are needed to understand the role of stigma in heightening the disproportionate harms experienced by WWUD.

Equine non-invasive time-lapse imaging and blastocyst development.

In this study we examined the timeline of mitotic events of invitro-produced equine embryos that progressed to blastocyst stage using non-invasive time-lapse microscopy (TLM). Intracytoplasmic sperm injection (ICSI) embryos were cultured using a self-contained imaging incubator system (Miri®TL; Esco Technologies) that captured brightfield images at 5-min intervals that were then generated into video for retrospective analysis. For all embryos that progressed to the blastocyst stage, the initial event of extrusion of acellular debris preceded all first cleavages and occurred at mean (±s.e.m.) time of 20.0±1.1h after ICSI, whereas 19 of 24 embryos that did not reach the blastocyst stage demonstrated debris extrusion that occurred at 23.8±1.1h, on average 4h longer for this initial premitotic event (P<0.05). Embryos that failed to reach the blastocyst stage demonstrated a 4-h delay compared with those that reached the blastocyst stage to reach the 2-cell stage (P<0.05). All embryos that reached the blastocyst stage expressed pulsation of the blastocyst with visible expansion and contraction at approximate 10-min intervals, or five to six times per hour. Using a logit probability method, we determined that 2- and 8-cell stage embryos could reasonably predict which embryos progressed to the blastocyst stage. Together, the results indicate that TLM for equine embryo development is a dynamic tool with promise for predicting successful embryo development.

Gold nanostar substrates for SERS-based chemical sensing in the femtomolar regime.

We report a novel approach for fabricating gold nanostar-functionalized substrates for highly sensitive surface enhanced Raman spectroscopy (SERS)-based chemical sensing. Gold nanostars immobilized on a gold substrate via a Raman silent organic tether serve as the SERS substrate, and facilitate the chemical sensing of analytes that can either be chemisorbed or physisorbed on the nanostars. Our SERS substrates are capable of detecting chemisorbed 4-mercaptobenzoic acid at a concentration as low as 10 fM with a reproducible SERS enhancement factor of 10(9), and enable the semi-quantitative multiplexed identification of analytes from mixtures in which they have been dissolved in variable stoichiometry. Most importantly, they afford the detection of physisorbed analytes, such as crystal violet, with an excellent signal-to-noise ratio, hence serving as a versatile platform for the chemical identification of in principle any molecular analyte. These characteristics make a strong case for the use of our nanostar-based SERS substrate in practical chemical sensing applications.

A high-resolution comparative map of porcine chromosome 4 (SSC4).

We used the IMNpRH2(12,000-rad) RH and IMpRH(7,000-rad) panels to integrate 2019 transcriptome (RNA-seq)-generated contigs with markers from the porcine genetic and radiation hybrid (RH) maps and bacterial artificial chromosome finger-printed contigs, into 1) parallel framework maps (LOD ≥ 10) on both panels for swine chromosome (SSC) 4, and 2) a high-resolution comparative map of SSC4, thus and human chromosomes (HSA) 1 and 8. A total of 573 loci were anchored and ordered on SSC4 closing gaps identified in the porcine sequence assembly Sscrofa9. Alignment of the SSC4 RH with the genetic map identified five microsatellites incorrectly mapped around the centromeric region in the genetic map. Further alignment of the RH and comparative maps with the genome sequence identified four additional regions of discrepancy that are also suggestive of errors in assembly, three of which were resolved through conserved synteny with blocks on HSA1 and HSA8.

Osmotic stress stimulates generation of superoxide anion by spermatozoa in horses.

The objective of this study was to examine the interplay between osmotic and oxidative stress as well as to determine mechanisms by which osmotic stress increases superoxide generation in spermatozoa of horses. Superoxide production, as measured by dihydroethidium (DHE), increased when spermatozoa of horses were incubated under either hyperosmotic or hyposmotic conditions. This increase in superoxide production was inhibited by the MAP kinase p38 inhibitor, SB203580, and by the superoxide scavenger, tiron. Incubation of spermatozoa under hyperosmotic conditions increased overall protein tyrosine phosphorylation as measured by western blotting techniques; however, a similar increase was not detected when spermatozoa were incubated under hyposmotic conditions. The general protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibitor staurosporine inhibited (P<0.05) tyrosine phosphorylation in samples from cells under hyperosmotic conditions. In addition, the NADPH oxidase inhibitor diphenyleneiodonium (DPI) also inhibited (P<0.05) protein tyrosine phosphorylation in cells under hyperosmotic conditions. In summary, these data indicate that incubation of equine spermatozoa under both hyposmotic and hyperosmotic conditions can increase superoxide anion generation. Under hyperosmotic conditions, this increased generation of superoxide anion was accompanied by increased protein tyrosine phosphorylation.

Biophysics of zebrafish (Danio rerio) sperm.

In the past two decades, laboratories around the world have produced thousands of mutant, transgenic, and wild-type zebrafish lines for biomedical research. Although slow-freezing cryopreservation of zebrafish sperm has been available for 30 years, current protocols lack standardization and yield inconsistent post-thaw fertilization rates. Cell cryopreservation cannot be improved without basic physiological knowledge, which was lacking for zebrafish sperm. The first goal was to define basic cryobiological values for wild-type zebrafish sperm and to evaluate how modern physiological methods could aid in developing improved cryopreservation protocols. Coulter counting methods measured an osmotically inactive water fraction (Vb) of 0.37+/-0.02 (SEM), an isosmotic cell volume (V(o)) of 12.1+/-0.2 microm(3) (SEM), a water permeability (L(p)) in 10% dimethyl sulfoxide of 0.021+/-0.001(SEM)microm/min/atm, and a cryoprotectant permeability (P(s)) of 0.10+/-0.01 (SEM)x10(-3)cm/min. Fourier transform infrared spectroscopy indicated that sperm membranes frozen without cryoprotectant showed damage and lipid reorganization, while those exposed to 10% glycerol demonstrated decreased lipid phase transition temperatures, which would stabilize the cells during cooling. The second goal was to determine the practicality and viability of shipping cooled zebrafish sperm overnight through the mail. Flow cytometry demonstrated that chilled fresh sperm can be maintained at 92% viability for 24h at 0 degrees C, suggesting that it can be shipped and exchanged between laboratories. Additional methods will be necessary to analyze and improve cryopreservation techniques and post-thaw fertility of zebrafish sperm. The present study is a first step to explore such techniques.

[Eye fundus autofluorescence technique in the early diagnosis of age-related macular degeneration].

Autofluorescence (AF) of the eye fundus is one of the most promising studies. AF provides specific molecular information on the retinal pigment epithelium and enables one to diagnose early phenotypic changes that are predictors for progression of age-related macular degeneration. Many investigations have demonstrated that AF is a valuable clinical technique that should be improved in order to have information accessible to a patient on the diagnosis and prediction of age-related macular degeneration.

Favorable glycemic response of type 2 diabetics to low-calorie cranberry juice.

Fruit and vegetable intake is typically low for type 2 diabetics, possibly due to a perceived adverse effect on glycemic control. Cranberry juice (CBJ) may represent an attractive means for increasing fruit intake and simultaneously affording positive health benefits. This single cross-over design compared metabolic responses of type 2 diabetics (n= 12) to unsweetened low-calorie CBJ (LCCBJ; 19 Cal/240 mL), carbohydrate sweetened normal calorie CBJ (NCCBJ; 120 Cal/240 mL), isocaloric low-calorie sugar water control (LCC), and isocaloric normal calorie sugar water control (NCC) interventions. CBJ flavonols and anthocyanins, and proanthocyanidins were quantified with HPLC, LC-MS, and MALDI-TOF that includes an original characterization of several large oligomeric proanthocyanidins. Blood glucose peaked 30 min postingestion after NCCBJ and NCC at 13.3 +/- 0.5 and 12.8 +/- 0.9 (mmol/L), and these responses were significantly greater than the LCCBJ and LCC peaks of 8.1 +/- 0.5 and 8.7 +/- 0.5, respectively. Differences in glycemic response remained significant 60 min, but not 120 min postingestion. Plasma insulin values 60 min postingestion for NCCBJ and NCC interventions were 140 +/- 19 and 151 +/- 18 (pmol/L), respectively, and significantly greater than the LCCBJ and LCC values of 56 +/- 10 and 54 +/- 10; differences were not significant 120 min postingestion. Metabolic responses within the 2 high and 2 low-calorie beverages were virtually identical; however, exposure to potentially beneficial nutrients was greater with CBJ. Relative to conventionally sweetened preparation, LCCBJ provides a favorable metabolic response and should be useful for promoting increased fruit consumption among type 2 diabetics or others wishing to limit carbohydrate intake.

Investigating the genetic basis of pork tenderness: genomic analysis of porcine CAST.

A quantitative trait locus (QTL) affecting pork tenderness was recently detected within the Illinois Meat Quality Pedigree (IMQP) and fine-mapped to the region of porcine chromosome 2 (SSC2) harbouring the functional candidate gene calpastatin (CAST). To identify molecular variation that may underlie the observed differences in tenderness phenotypes, we characterized the porcine CAST gene and analysed allelic variation within the F(1) boars of the IMQP. The complete genomic sequence of porcine CAST has been determined, and was found to contain 35 exons spanning nearly 123 kb. Using the rapid amplification of cDNA ends (RACE) method, calpastatin transcript types I-III, as well as a putative novel transcript type, were detected within porcine skeletal muscle. Variability in transcription initiation and termination sites was observed, and alternative splicing of exons 1y and 3 was evident. Nearly 77.6% of the CAST gene, including all exons, was re-sequenced from each of six IMQP F(1) boars, and almost 900 polymorphisms were identified. The heterozygosity of nearly 400 polymorphisms appeared to be concordant with the previous QTL data, and the location of this variation within the CAST gene suggests that a causative mutation is likely to be regulatory. Functional characterization of CAST variation should enhance understanding of the molecular basis of pork tenderness, and thus allow for genetic improvement of pork products. The effectiveness of CAST polymorphisms for marker-assisted selection of pork tenderness can now be assessed.

High-resolution comprehensive radiation hybrid maps of the porcine chromosomes 2p and 9p compared with the human chromosome 11.

We are constructing high-resolution, chromosomal 'test' maps for the entire pig genome using a 12,000-rad WG-RH panel (IMNpRH2(12,000-rad))to provide a scaffold for the rapid assembly of the porcine genome sequence. Here we present an initial, comparative map of human chromosome (HSA) 11 with pig chromosomes (SSC) 2p and 9p. Two sets of RH mapping vectors were used to construct the RH framework (FW) maps for SSC2p and SSC9p. One set of 590 markers, including 131 microsatellites (MSs), 364 genes/ESTs, and 95 BAC end sequences (BESs) was typed on the IMNpRH2(12,000-rad) panel. A second set of 271 markers (28 MSs, 138 genes/ESTs, and 105 BESs) was typed on the IMpRH(7,000-rad) panel. The two data sets were merged into a single data-set of 655 markers of which 206 markers were typed on both panels. Two large linkage groups of 72 and 194 markers were assigned to SSC2p, and two linkage groups of 84 and 168 markers to SSC9p at a two-point LOD score of 10. A total of 126 and 114 FW markers were ordered with a likelihood ratio of 1000:1 to the SSC2p and SSC9p RH(12,000-rad) FW maps, respectively, with an accumulated map distance of 4046.5 cR(12,000 )and 1355.2 cR(7,000 )for SSC2p, and 4244.1 cR(12,000) and 1802.5 cR(7,000) for SSC9p. The kb/cR ratio in the IMNpRH2(12,000-rad) FW maps was 15.8 for SSC2p, and 15.4 for SSC9p, while the ratio in the IMpRH(7,000-rad) FW maps was 47.1 and 36.3, respectively, or an approximately 3.0-fold increase in map resolution in the IMNpRH(12,000-rad) panel over the IMpRH(7,000-rad) panel. The integrated IMNpRH(12,000-rad) andIMpRH(7,000-rad) maps as well as the genetic and BAC FPC maps provide an inclusive comparative map between SSC2p, SSC9p and HSA11 to close potential gaps between contigs prior to sequencing, and to identify regions where potential problems may arise in sequence assembly.

Applications of chitosan for improvement of quality and shelf life of foods: a review.

Chitosan is a modified, natural biopolymer derived by deacetylation of chitin, a major component of the shells of crustacean. Recently, chitosan has received increased attention for its commercial applications in the biomedical, food, and chemical industries. Use of chitosan in food industry is readily seen due to its several distinctive biological activities and functional properties. The antimicrobial activity and film-forming property of chitosan make it a potential source of food preservative or coating material of natural origin. This review focuses on the applications of chitosan for improvement of quality and shelf life of various foods from agriculture, poultry, and seafood origin.

Melorheostosis involving the cervical and upper thoracic spine: radiographic, CT, and MR imaging findings.

Melorheostosis, an uncommon mesenchymal dysplasia, rarely affects the axial skeleton. We describe the imaging findings of melorheostosis involving the cervical and upper thoracic spine. Radiographs and CT showed unilateral well-marginated undulating zones of cortical hyperostosis involving multiple vertebrae that were contiguous with a coalescent ossified right paravertebral mass. MR imaging showed zones of signal intensity void on all pulse sequences without contrast enhancement. Conservative management was elected because of lack of interval clinical and imaging changes for 8 years.

Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes.

BACKGROUND AND PURPOSE: Primary atypical teratoid/rhabdoid tumors (AT/RTs) are rare malignant intracranial neoplasms, usually occurring in young children. The objectives of this study were to characterize the MR imaging features and locations of primary intracranial AT/RTs, to determine the frequency of disseminated disease in the central nervous system (CNS) at diagnosis and postoperatively, and to assess patient outcomes. METHODS: The preoperative cranial MR images of 13 patients with AT/RTs were retrospectively reviewed for evaluation of lesion location, size, MR signal intensity and enhancement characteristics, and the presence of disseminated intracranial tumor. Postoperative MR images of the head and spine for 17 patients were reviewed for the presence of locally recurrent or residual tumor and disseminated neoplasm. Imaging data were correlated with patient outcomes. RESULTS: Patients ranged in age from 4 months to 15 years (median age, 2.9 years). Primary AT/RTs were intra-axial in 94% of patients. The single primary extra-axial lesion was located in the cerebellopontine angle cistern. AT/RTs were infratentorial in 47%, supratentorial in 41%, and both infra- and supratentorial in 12%. A germ-line mutation of the hSNF5/INI1 tumor-suppressor gene was responsible for the simultaneous occurrence of an intracranial AT/RT and a malignant renal rhabdoid tumor in a 4-month-old patient. Mean tumor sizes were 3.6 x 3.8 x 3.9 cm. On short TR images, AT/RTs typically had heterogeneous intermediate signal intensity, as well as zones of low (54%), high (8%), or both low and high (31%) signal intensity from cystic and/or necrotic regions, hemorrhage, or both, respectively. On long TR/long TE images, solid portions of AT/RTs typically had heterogeneous intermediate-to-slightly-high signal intensity with additional zones of high (54%) or both high and low signal intensity (38%), secondary to cystic and/or necrotic regions, edema, prior hemorrhage, and/or calcifications. AT/RT had isointense and/or slightly hyperintense signal intensity relative to gray matter on fluid-attenuated inversion-recovery (FLAIR) and long TR/long TE images, and showed restricted diffusion. All except 1 AT/RT showed contrast enhancement. The fraction of tumor volume showing enhancement was greater than two thirds in 58%, between one third and two thirds in 33%, and less than one third in 9%. Disseminated tumor in the leptomeninges was seen with MR imaging in 24% of patients at diagnosis/initial staging and occurred in another 35% from 4 months to 2.8 years (mean, 1.1 years) after surgery and earlier imaging examinations with negative findings. The overall 1-year and 5-year survival probabilities were 71% and 28%, respectively. Patients with MR imaging evidence of disseminated leptomeningeal tumor had a median survival rate of 16 months compared with 149 months for those without disseminated tumor (P < .004, logrank test). CONCLUSION: AT/RTs are typically intra-axial lesions, which can be infra- and/or supratentorial. The unenhanced and enhanced MR imaging features of AT/RT are often variable secondary to cystic/necrotic changes, hemorrhage, and/or calcifications. Poor prognosis is associated with MR imaging evidence of disseminated leptomeningeal tumor.

A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep.

Ovine hereditary chondrodysplasia, or spider lamb syndrome (SLS), is a genetic disorder that is characterized by severe skeletal abnormalities and has resulted in substantial economic losses for sheep producers. Here we demonstrate that a non-synonymous T>A transversion in the highly conserved tyrosine kinase II domain of a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3), is responsible for SLS. We also demonstrate that the mutant FGFR3 allele has an additive effect on long-bone length, calling into question the long-standing belief that SLS is inherited as a strict monogenic, Mendelian recessive trait. Instead, we suggest that SLS manifestation is determined primarily by the presence of the mutant FGFR3 allele, but it is also influenced by an animal's genetic background. In contrast to FGFR3 mutations causing dwarfism in humans, this single-base change is the only known natural mutation of FGFR3 that results in a skeletal overgrowth phenotype in any species.

Capacitation-like changes in equine spermatozoa following cryopreservation.

The primary objective of this study was to assess plasma membrane characteristics and activation of signal transduction pathways in equine spermatozoa during both in vitro capacitation and cryopreservation. Significant plasma membrane restructuring, as assessed by measurement of plasma membrane lipid disorder and phospholipid scrambling, was not observed until after cryopreservation and subsequent thawing (P < 0.05). Although in vitro capacitated cells also displayed increased plasma membrane lipid disorder and phospholipid scrambling (P < 0.05), it appeared that regulation of these events in in vitro capacitated versus cryopreserved equine spermatozoa was not identical. Addition of 5 microM staurosporine to the capacitation media reduced plasma membrane phospholipid scrambling (P < 0.05), but supplementation to the freezing extender prior to cryopreservation did not. Furthermore, progesterone was able to induce a greater degree of acrosomal exocytosis in in vitro capacitated versus frozen/thawed spermatozoa. Expression of phospholipid scramblase, a protein thought to be important in plasma membrane phospholipid scrambling, did not differ between treatments. Comparison of protein tyrosine phosphorylation patterns between in vitro capacitated and cryopreserved cells demonstrated a divergence in signal transduction. Cellular signaling in in vitro capacitated equine spermatozoa appeared to be in part dependent on activation of the cAMP/PKA pathway, whereas signaling in cryopreserved cells seemed to proceed predominantly through alternative pathways. Taken together, these data support the idea that capacitation and "cryocapacitation" are not equivalent processes.

Equine sperm membrane phase behavior: the effects of lipid-based cryoprotectants.

The plasma membrane of sperm can undergo lipid phase separation during freezing, resulting in irreversible damage to the cell. The objective of our study was to examine the membrane phase behavior of equine spermatozoa in the absence and presence of lipid-based cryoprotectants. Biophysical properties of sperm membranes were investigated with Fourier-transform infrared spectroscopy. Compared to fresh untreated sperm, postthaw untreated sperm showed extensive lipid phase separation and rearrangement. In contrast, postthaw sperm that were cryopreserved in egg phosphatidylcholine (egg PC)- or soy phosphatidylcholine (soy PC)-based diluents showed similar lipid phase behavior to that of fresh, untreated sperm. Studies with a deuterium-labeled PC lipid (POPCd-31) suggest that exogenous lipid from the diluents are strongly associated with the sperm membrane, and scanning electron microscopy images of treated sperm show the presence of lipid aggregates on the membrane surface. Thus, the exogenous lipid does not appear to be integrated into the sperm membrane after cryopreservation. When compared to a standard egg-yolk-based diluent (INRA 82), the soy and egg PC media preserved viability and motility equally well in postthaw sperm. A preliminary fertility study determined that sperm cryopreserved in the soy PC-based medium were capable of fertilization at the same rate as sperm frozen in the conventional INRA 82 medium. Our results show that pure lipid-based diluents can prevent membrane damage during cryopreservation and perform as well as a standard egg-yolk-based diluent in preserving sperm viability, motility, and fertility.