Involvement of a chaperone regulator, Bcl2-associated athanogene-4, in apolipoprotein B mRNA editing.
Apobec-1 is the catalytic subunit of a multicomponent editosome complex that mediates apolipoprotein B (apoB) mRNA editing. We isolated a novel apobec-1-interacting protein by yeast two-hybrid cloning and identified the protein as BAG-4. BAG-4, a chaperone-regulating protein, also known as SODD (silencer of death domains), is a member of the BAG family of proteins. In this report, we found that apobec-1 is localized in the perinucleolar compartment in HepG2 cells and rat liver MCR-RH7777 cells. BAG-4 binds to apobec-1 via its N-terminal region independent of the BAG domain. It is ubiquitously expressed with predominant occurrence in human pancreas, heart, brain, and placenta. Immunoprecipitation experiments confirmed that BAG-4 interacts with Hsc70/Hsp90 in HepG2 cells. BAG-4 tagged with green fluorescent protein (GFP) or FLAG was localized both in cytoplasm of mouse BNLCL.2 liver cells and human liver hepatoma HepG2 cells. After heat shock, GFP-BAG-4 co-localizes with Hsc70 in the nucleus in HepG2 cells, whereas GFP-BAG-4 mutants lacking the BAG domain remain perinuclear. BAG-4 has no effects on apoB mRNA editing in vitro. However, unlike other apobec-1 complementation factors studied to date, antisense knockdown of BAG-4 in BNLCL.2 cells and in MCR-RH7777 cells increases rather than decreases endogenous apoB mRNA editing. Overexpression of BAG-4 in MCR-RH7777 cells also suppresses apoB mRNA editing. ApoB-48 production also increases with antisense BAG-4 expression in MCR-RH7777 cells. We previously showed that apoB mRNA editing is an intranuclear event (Lau, P. P., Xiong, W. J., Zhu, H. J., Chen, S. H., and Chan, L. (1991) J. Biol. Chem. 266, 20550-20554). Thus, BAG-4 overexpression down-regulates apoB mRNA editing by shuttling apobec-1 from the intranuclear perinucleolar compartment to the cytoplasm. We propose that BAG-4 functions as a negative regulator for apobec-1-mediated apoB mRNA editing through its ability to suppress the Hsp/Hsc70 chaperone activity and thereby editosome formation and, as a consequence, prevents nuclear localization of the apobec-1 editosome.


Tuberculomas presenting as isolated intrinsic brain stem masses.
We document the clinical presentation, management and outcome of histologically verified, solitary, intrinsic brain stem tuberculomas in six patients. The neurological symptoms and signs in these patients did not distinguish their lesions from other intrinsic masses of the brain stem. On contrast-enhanced computed tomography (CT), the tuberculomas appeared as ring enhancing lesions in three patients and nodular contrast enhancing lesions in the other three. Diagnosis was established on the basis of CT-guided stereotactic biopsy in all patients. All patients were treated with antituberculous drugs for 18 months. Steroid therapy of 2-8 weeks duration was also used in four patients. At a median follow-up period of 20 months (range 9-51 months), three patients were asymptomatic and the other three were functioning independently with mild disability. Although isolated, intrinsic brain stem tuberculoma is an uncommon entity, it should be suspected in patients presenting with features of an intrinsic brain stem mass and a contrast-enhancing lesion on CT. CT-guided stereotactic biopsy usually provides evidence of the inflammatory nature of the mass although an aetiological diagnosis is often elusive. Early diagnosis and appropriate therapy with antituberculous drugs and steroids usually results in an excellent or good outcome in most instances.


Impact of Schistosoma haematobium infection and of praziquantel treatment on anaemia of primary school children in Bertoua, Cameroon.
There is some debate as to the extent to which Schistosoma haematobium haematuria may be the cause of anaemia. Our goal was to evaluate the impact of a single 40 mg kg-1 dose of praziquantel on anaemia. Since praziquantel does not reduce the hookworm intensity of infection (a major cause of anaemia in children in the area) changes in the prevalence of anaemia in the study population should be due only to the elimination of S. haematobium. Seven hundred and seventy-one primary schoolboys from Bertoua (East Cameroon) were divided into four groups: high infection, moderate infection treated with praziquantel or placebo, and non-infected. Haemoglobin concentrations of the children were determined at the onset of the study and 6 months after the praziquantel intervention. Mean haemoglobin concentrations were not significantly different for no infection or for mild or heavy infection by S. haematobium. A factorial analysis of variance using S. haematobium intensity of infection, malaria and intestinal parasite infections and age as independent variables and haemoglobin concentration as the dependent variable show that only age and malaria infection show a significant relationship with haemoglobin concentration. Despite treatment with praziquantel, all the children in the treatment groups had lower mean haemoglobins 6 months after intervention. A factorial analysis of variance using age, malaria infection and the treatment category as independent variables and the difference in haemoglobin concentration as the dependent variable shows that only malaria infection showed a significant relationship with haemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)


Consistent codling moth population decline by two years of mating disruption in apple: a Flemish case study.
Codling moth (Cydia pomonella) is one of the most important pests in apple and pear. In 2010 mating disruption became a key pest management tactic in Flemish pip fruit orchards, largely due to a government subsidy and demonstrating projects aiming to widen the area treated by pheromones as large as possible. As a consequence, the mating disruption strategy was applied at approximately 7.500 ha, or half of the pip fruit area, in 2010 and 2011. The sudden large-scale implementation of this technique changed the codling moth management landscape. Here we present a case study of a commercially managed orchard that suffered from high codling moth pressures for many years, as did the surrounding area. The RAK3 mating disruption system was introduced at this location in 2010, and was continued in 2011. Systematic detailed codling moth flight data for this location are available for many years. In addition, comprehensive data on damage levels of chemically untreated windows spread all over the test orchard in a randomized block design were obtained in successive years, enabling us to thoroughly evaluate the effect of the changed codling moth management strategy. Data from 2011 included damage levels in chemically treated windows when the entire orchard was applied once at the flight peak of Cydia pomonella. In 2009, before introduction of mating disruption, a mean of 8.25 +/- 5.54% of the fruits were infested at harvest when assessed in completely untreated windows. After two years of mating disruption, supported with a full chemical support in 2010, except for the untreated assessment windows, and only one application on the flight peak of 2011, damage was reduced to less than 0.03% at harvest. This is a valuable case study to demonstrate the benefits of the mating disruption approach.


Mechanistic aspects of ameliorative effects of Eicosapentanoic acid ethyl ester on methotrexate-evoked testiculopathy in rats.
Disrupted spermatogenesis and testicular injury are among the devastating outcomes of methotrexate. A major contributor to methotrexate-induced testiculopathy is oxidative damage which triggers apoptosis and altered autophagy responses. Eicosapentaenoic acid ethyl ester (EPA-E) is an antihyperlipidemic derivative of omega-3 fatty acids that exhibited affinity to peroxisome proliferator-activated receptor-γ (PPAR-γ) that possesses both antioxidant and autophagy modulating properties. This is an exploratory study aiming at assessing the effectiveness of EPA-E to alleviate testicular damage induced by methotrexate. The specific exploratory hypothesis of this experiment is: EPA-E administration for 1 week to methotrexate-treated rats reduces testicular damage compared to control rats. As a secondary outcome, we were interested in identifying the implicated mechanism that mediates the action of EPA-E. In adult male Wistar rats, testiculopathy was achieved by a single methotrexate injection (20 mg/kg, ip). Rats received vehicle, EPA-E (0.3 g/kg/day, po) alone or with selective PPAR-γ antagonist (bisphenol A diglycidyl ether, BADGE) at 30 mg/kg/day, ip for 1 week. EPA-E recuperated methotrexate-attenuated serum total testosterone while reduced testicular inflammation and oxidative stress, restoring superoxide dismutase (SOD) while reducing malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Methotrexate-induced testicular apoptosis (caspase-3 and p53) was suppressed upon EPA-E treatment. Besides, EPA-E curbed methotrexate-induced abnormal autophagy by downregulating LC3A/B and beclin-1. Interestingly, BADGE-coadministration reversed EPA-E beneficial actions. Collectively, our findings suggest PPAR-γ role in EPA-E-mediated mitigation of methotrexate-evoked testiculopathy via suppression of oxidative stress, apoptosis, as well as abnormal autophagy. Furthermore, EPA-E could be used as a preventive therapy for some testiculopathies mediated by oxidative stress.


Acute responses and muscle damage in different high-intensity interval running protocols.
Our study aimed to evaluate the acute responses and exercise-induced muscle damage of five different high-intensity interval training (HIIT) protocols adjusted by the maximum velocity obtained in the 30-15 Intermittent Fitness Test (VIFT). Sixteen well-trained intermittent sport players (mean ± SD; age, 24.6±2.7 years; V̇O2max, 58.3±5.9 mL/kg/min) participated in five different HIIT protocols separated by six days in between (P240: 4×4 min at 80% VIFT; P120: 7×2 min at 85%; P30: 2×10×30 s at 90%; P15: 3×9×15 s at 95%; P5: 4×6×5 s sprints). Blood lactate (La), blood pH, serum creatine kinase (CK), heart rate (HR), session rating of perceived exertion (session-RPE), delayed onset muscle soreness (DOMS) and countermovement jump (CMJ) height were measured. A significant main effect for protocol (P<0.05) was found for the acute responses of HR, session-RPE and La with values increasing in longer intervals from P15 to P120 and P240 while blood pH responded inversely. In contrast, P5 produced the highest La concentration and blood pH decreases. Twenty-four-hour post-exercise CK, DOMS and the decrease in CMJ height were significantly higher after P5 compared to all other protocols (P<0.05). HIIT protocols of different interval duration and intensity result in varying acute physiological and perceptual demands and exercise-induced muscle damage. Longer intervals with submaximal intensity lead to higher acute cardio circulatory responses, whereas sprint protocols induce the highest muscle damage and muscle soreness.


Production of interleukin-6 by folliculo-stellate cells of the anterior pituitary gland in a histiotypic cell aggregate culture system.
Reaggregate cell cultures of mouse or rat anterior pituitary were found to produce interleukin-6 (IL-6), a cytokine known for its multiple actions in the immune system. Studies on aggregates prepared from differentially enriched pituitary cell populations revealed the presence of folliculo-stellate (FS) cells to be essential for IL-6 production. Aggregates that contained only hormone-secreting, but no FS cells, failed to produce IL-6. Furthermore, the yield of IL-6 increased with increasing proportions of FS cells present in the aggregates. It is suggested that IL-6 participates in the local regulation of the secretory function of the hypophysis and may constitute a link between events in the immune system and those in the endocrine system.


Jammed frictionless disks: Connecting local and global response.
By calculating the linear response of packings of soft frictionless disks to quasistatic external perturbations, we investigate the critical scaling behavior of their elastic properties and nonaffine deformations as a function of the distance to jamming. Averaged over an ensemble of similar packings, these systems are well described by elasticity, while in single packings we determine a diverging length scale l* up to which the response of the system is dominated by the local packing disorder. This length scale, which we observe directly, diverges as 1/Deltaz , where Deltaz is the difference between contact number and its isostatic value, and appears to scale identically to the length scale which had been introduced earlier in the interpretation of the spectrum of vibrational modes. It governs the crossover from isostatic behavior at the small scale to continuum behavior at the large scale; indeed we identify this length scale with the coarse graining length needed to obtain a smooth stress field. We characterize the nonaffine displacements of the particles using the displacement angle distribution, a local measure for the amount of relative sliding, and analyze the connection between local relative displacements and the elastic moduli.


T-lymphocyte tumor necrosis factor-alpha receptor binding in patients with Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system (CNS), in which the cytokine network may be deranged, leading to an altered immunoregulation. Tumor necrosis factor(TNF)-alpha, a cytokine with pleiotropic neuroimmune effects, has specific receptors on human lymphocytes, as well as on other cell types, even in the CNS. The aim of the present study was to assay TNF-alpha binding on peripheral blood T cells from PD patients, as compared with healthy subjects. We found on T lymphocytes from parkinsonian patients significantly more TNF-alpha receptors than on those from controls (B (max): 637+/-23 vs. 131+/-6 (mean+/-S.E.M.) receptors/cell). Such TNF-alpha binding sites are of the same type in patients and healthy subjects (K(d): 66.8+/-5.1 vs. 70.7+/-5.6 (mean+/-S.E.M.) pM). These results are discussed in terms of PD immunopathogenesis, since it has been reported that activated T lymphocytes have increased amounts of TNF-alpha receptors.


Reduced genotoxicity of avian sarcoma leukosis virus vectors in rhesus long-term repopulating cells compared to standard murine retrovirus vectors.
Insertional mutagenesis continues to be a major concern in hematopoietic stem-cell gene therapy. Nonconventional gene transfer vectors with more favorable integration features in comparison with conventional retrovirus and lentivirus vectors are being developed and optimized. In this study, we report for the first time a systematic analysis of 198 avian sarcoma leukosis virus (ASLV) insertion sites identified in rhesus long-term repopulating cells, and a comparison of ASLV insertion patterns to Moloney murine leukemia virus (MLV) (n = 396) and simian immunodeficiency virus (SIV) (n = 289) using the newly released rhesus genome databank. Despite a weak preference toward gene-coding regions, ASLV integration is nonclustered, does not favor gene-rich regions, transcription start sites, or CpG islands. There was no propensity for ASLV insertions within or near proto-oncogenes, and most importantly, no insertions close to or within the Mds1-Evi1 locus, which is in contrast to the significant over-representation of this insertion site for MLV vectors in the same transplantation model. Furthermore, ASLV long terminal repeats (LTRs) do not have detectable promoter and enhancer activity in a quantitative luciferase assay to measure neighboring gene activation. The combination of these features is unique for ASLV and suggests that optimized vectors based on this virus could be useful and safe for gene transfer to hematopoietic stem cells and progenitor cells.


Effect of exercise, training, circadian rhythm, age, and sex on insulin-like growth factor-1 in the horse.
Insulin-like growth factor-1 could be a useful marker in the horse for diagnostic, selection, or forensic purposes, provided its physiological regulation is well understood. The objective of this study was to investigate factors, such as acute exercise, fitness training, time of day, sex, and age, that may influence serum IGF-1 in normal, healthy horses. Throughout a 9-wk training program, 6 geldings maintained a mean (+/- SEM) IGF-1 concentration of 302 +/- 29 ng/mL. Moderate or high intensity exercise had no effect on IGF-1 concentrations, when pre- and postexercise values were compared. Over a 24-h period, there was some variation in IGF-1 concentrations but no clear diurnal rhythm. Concentrations of IGF-1 were measured in a large population of thoroughbred horses (1,880) on 3 continents. The population deviated slightly from a normal distribution (P < 0.001) because of large IGF-1 concentrations in 10 horses. The global mean IGF-1 concentration was 310 +/- 2.2 ng/mL, with a greater mean value (P < 0.001) in gonad-intact males (336 +/- 5.6 ng/mL) than in females (303 +/- 3.2 ng/mL) or geldings (302 +/- 3.2 ng/mL). However, the greatest IGF-1 concentrations observed for all stallions, mares, and geldings were 627, 676, and 709 ng/mL, respectively. In mares and geldings, IGF-1 concentrations showed a gradual decrease with advancing age (P < 0.001), but the effect was much less marked in stallions. This study confirms that IGF-1 concentrations are stable, compared with GH concentrations, in the horse and that a meaningful measure of IGF-1 status can be obtained from a daily serum sample.


A Polysaccharide Isolated from Codonopsis pilosula with Immunomodulation Effects Both In Vitro and In Vivo.
In this study, an acidic polysaccharide from Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-β-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of β-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4+/CD8+ T lymphocyte ratio. These results suggest that β-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.


Integrating bioassays and analytical chemistry as an improved approach to support safety assessment of food contact materials.
Food contact materials (FCM) contain chemicals which can migrate into food and result in human exposure. Although it is mandatory to ensure that migration does not endanger human health, there is still no consensus on how to pragmatically assess the safety of FCM since traditional approaches would require extensive toxicological and analytical testing which are expensive and time consuming. Recently, the combination of bioassays, analytical chemistry and risk assessment has been promoted as a new paradigm to identify toxicologically relevant molecules and address safety issues. However, there has been debate on the actual value of bioassays in that framework. In the present work, a FCM anticipated to release the endocrine active chemical 4-nonyphenol (4NP) was used as a model. In a migration study, the leaching of 4NP was confirmed by LC-MS/MS and GC-MS. This was correlated with an increase in both estrogenic and anti-androgenic activities as measured with bioassays. A standard risk assessment indicated that according to the food intake scenario applied, the level of 4NP measured was lower, close or slightly above the acceptable daily intake. Altogether these results show that bioassays could reveal the presence of an endocrine active chemical in a real-case FCM migration study. The levels reported were relevant for safety assessment. In addition, this work also highlighted that bioactivity measured in migrate does not necessarily represent a safety issue. In conclusion, together with analytics, bioassays contribute to identify toxicologically relevant molecules leaching from FCM and enable improved safety assessment.


Clonal Dissemination of OXA-232 Carbapenemase-Producing Klebsiella pneumoniae in Neonates.
Five OXA-232 carbapenemase-producing Klebsiella pneumoniae isolates, belonging to the pandemic clone sequence type 15 (ST15), were isolated from neonates and coproduced blaCTX-M-15 and blaSHV-1 genes. All isolates were resistant to ertapenem (MICs of >32 μg/ml) and meropenem (MICs of 4 to 8 μg/ml) and susceptible or intermediate to imipenem (MICs of 1 to 2 μg/ml). The blaOXA-232 gene was located on a ColE-type transformable plasmid of 6,141 bp. To the best of our knowledge, this is the first report of OXA-232 carbapenemase among clinical isolates in China.


[Characterization of ovarian adrenal rest tumors in children and adolescent females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency].
To summarize the characterization of ovarian adrenal rest tumors (OART) in children and adolescent females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). We have diagnosed 4 cases of CAH 21-OHD with OART in the recent 5 years in pediatric endocrinology unit of the first affiliated hospital of Sun Yat-Sen University. Clinical characterizations were summarized, including symptoms, growth patterns and bone age advancements, serum steroid concentrations, imaging results and the follow-up data. The 4 cases of OART accounted for 2.5 % of the CAH 21-OHD girls, which was much lower than the detection rate, 29.5%, of testicular ART in our patient group during the same period. The 4 cases included 3 salt wasters and 1 with simple virilizm. OART were diagnosed at the age of 8.9 years, 15.8 years, 21.4 years and 9.3 years, respectively. Before the diagnosis of OART, their daily hydrocortisone doses reached 16 mg/(m(2)·d)to 24 mg/(m(2)·d). The patients presented with deteriorated acne, deepened voice, amenorrhea (2 cases), accelerated growth and advanced bone age, ΔBA/ΔCA reached 1.2(during GnRHa treatment)and 2.0. Their serum adrenal steroids increased significantly and hyperplasia of adrenal glands were found in all patients. The diagnosis could be confirmed before the operation in only 1 case. The diagnosis could not be made until the planned sub-total adrenalectomy in the other 3 cases. The follow-up periods of OART were 4.8, 4.7, 3.8 and 2.7 years, respectively. Removal of OART resulted in symptoms relief at least partialy and lowered daily hydrocortisone doses, 14 to 19 mg/(m(2)·d). The detection rate of OART was much lower than testicular ART. Before the diagnosis of OART, the patients presented with deteriorated virilescence, accelerated growth and advanced bone age, elevated serum adrenal steroids and hyperplasia of adrenal glands. Removal of the OART resulted in symptoms relief at least partialy.


Comprehensive Analysis of Key m6A Modification Related Genes and Immune Infiltrates in Human Aortic Dissection.
To identify the feature of N6-methyladenosine (m6A) methylation modification genes in acute aortic dissection (AAD) and explore their relationships with immune infiltration. The GSE52093 dataset including gene expression data from patients with AAD and healthy controls was downloaded from Gene Expression Omnibus (GEO) database in order to obtain the differentially expressed genes (DEGs). The differentially methylated m6A genes were obtained from the GSE147027 dataset. The differentially expressed m6A-related genes were obtained based on the intersection results. Meanwhile, the protein-protein interaction (PPI) network of differentially expressed m6A-related genes was constructed, and hub genes with close relationships in the network were selected. Later, hub genes were verified by using the GSE153434 dataset. Thereafter, the relationships between these genes and immune cells infiltration were analyzed. A total of 279 differentially expressed m6A-related genes were identified in the GSE52093 and GSE147027 datasets. Among them, 94 genes were up-regulated in aortic dissection (AD), while the remaining 185 were down-regulated. As indicated by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, these genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs). The seven hub genes, namely, DDX17, CTGF, FLNA, SPP1, MYH11, ITGA5 and CACNA1C, were all confirmed as the potential biomarkers for AD. According to immune infiltration analysis, it was found that hub genes were related to some immune cells. For instance, DDX17, FLNA and MYH11 were correlated with Macrophages M2. Our study identifies hub genes of AD that may serve as the potential biomarkers, illustrates of the molecular mechanism of AD, and provides support for subsequent research and treatment development.


Systematic review of breastfeeding and herbs.
Despite popular and historical use, there has been little modern research conducted to determine the safety and efficacy of herb use during breastfeeding. The purpose of this study was to systematically review the clinical literature on herbal medicine and lactation. The databases PubMed, CAB Abstracts, Cochrane Central Register of Controlled Trials, HealthSTAR, Cumulative Index to Nursing and Allied Health Literature, and Reprotox were systematically searched for human trials from 1970 until 2010. Reference lists from relevant articles were hand-searched. Thirty-two studies met the inclusion criteria. Clinical studies were divided into three categories: survey studies (n=11), safety studies (n=8), and efficacy studies (n=13). Six studies were randomized controlled trials. The most common herbs studied were St. John's wort (Hypericum perforatum L.) (n=3), garlic (Allium sativum L.) extract (n=2), and senna (Cassia senna L.) (n=2). Studies were very heterogeneous with regard to study design, herbal intervention, and outcome measures. Overall, poor methodological quality predominated among the studies. Our review concludes that further research is needed to assess the prevalence, efficacy, and safety of commonly used herbs during breastfeeding.


Scaphoid nonunion.
Scaphoid nonunion is common, but the exact pathophysiology of this complication is unclear. Explanations include lack of treatment, poor initial treatment, delay in diagnosis, synovial fluid dynamics, precarious vascularity, fracture displacement, and carpal instability. Currently, the diagnosis is best confirmed by classic changes on plain radiographs, instability testing, arthrography, and arthroscopy in selected cases. Nine carpal bones are not benign. The natural history of scaphoid nonunion is one of progressive arthritis. Attempts at obtaining bony healing are therefore recommended. In treating established nonunions without arthritis, the Russe bone graft technique is the mainstay of treatment. A union rate of 90 per cent is to be expected. Electrical stimulation is an alternative when there is no synovial pseudarthrosis or scaphoid collapse deformity, or if a previous Russe graft has failed. If a significant humpback scaphoid or collapse deformity is present, internal fixation with the Herbert screw and scaphoid reconstruction with a bone graft are our choices. Healing rates are less than those with the Russe graft, but one may achieve improved motion of the wrist and earlier return to function. When scaphoid nonunion is accompanied by degenerative arthritis, salvage procedures are recommended. Radial styloidectomy is a simple procedure that will preserve motion and buy time. Soft tissue interposition with excision of a small proximal pole is useful, particularly if no collapse deformity is present. Silicone replacement alone has fallen into increasing disfavor because of the high incidence of subluxation and silicone synovitis. Combining silicone replacement with intercarpal fusion (the SLAC procedure) may lessen these complications. Proximal row carpectomy is another procedure that may preserve motion, though often at the expense of weakness, particularly in the younger patient requiring significant grip strength. In these cases, standard wrist fusion seems the most predictable alternative.


nBu4NI-Mediated oxidation of methyl ketones to α-ketoamides: using ammonium, primary and secondary amine-salt as an amine moiety.
Presented here is the first example of synthesizing an array of primary-, secondary-, and tertiary-α-ketoamides with a non-metal catalyst nBu4NI from methyl ketones and inexpensive readily available amine/ammonium salts; the reactions proceeded smoothly under mild conditions, TBHP was used as an oxidant and the corresponding α-ketoamides were afforded in moderate to excellent yields.


Traceless affinity labeling of endogenous proteins for functional analysis in living cells.
Protein labeling and imaging techniques have provided tremendous opportunities to study the structure, function, dynamics, and localization of individual proteins in the complex environment of living cells. Molecular biology-based approaches, such as GFP-fusion tags and monoclonal antibodies, have served as important tools for the visualization of individual proteins in cells. Although these techniques continue to be valuable for live cell imaging, they have a number of limitations that have only been addressed by recent progress in chemistry-based approaches. These chemical approaches benefit greatly from the smaller probe sizes that should result in fewer perturbations to proteins and to biological systems as a whole. Despite the research in this area, so far none of these labeling techniques permit labeling and imaging of selected endogenous proteins in living cells. Researchers have widely used affinity labeling, in which the protein of interest is labeled by a reactive group attached to a ligand, to identify and characterize proteins. Since the first report of affinity labeling in the early 1960s, efforts to fine-tune the chemical structures of both the reactive group and ligand have led to protein labeling with excellent target selectivity in the whole proteome of living cells. Although the chemical probes used for affinity labeling generally inactivate target proteins, this strategy holds promise as a valuable tool for the labeling and imaging of endogenous proteins in living cells and by extension in living animals. In this Account, we summarize traceless affinity labeling, a technique explored mainly in our laboratory. In our overview of the different labeling techniques, we emphasize the challenge of designing chemical probes that allow for dissociation of the affinity module (often a ligand) after the labeling reaction so that the labeled protein retains its native function. This feature distinguishes the traceless labeling approach from the traditional affinity labeling method and allows for real-time monitoring of protein activity. With the high target specificity and biocompatibility of this technique, we have achieved individual labeling and imaging of endogenously expressed proteins in samples of high biological complexity. We also highlight applications in which our current approach enabled the monitoring of important biological events, such as ligand binding, in living cells. These novel chemical labeling techniques are expected to provide a molecular toolbox for studying a wide variety of proteins and beyond in living cells.


Comparison of a Medical-Grade Monitor vs Commercial Off-the-Shelf Display for Mitotic Figure Enumeration and Small Object (Helicobacter pylori) Detection.
To examine the performance of a commercial off-the-shelf (COTS) monitor vs a medical-grade (MG) monitor for small object enumeration in standardized digital pathology images. Pathologists reviewed 35 melanoma or 35 gastric biopsy images using the MG and COTS displays, with a 2-week washout period. Mitotic figure or Helicobacter pylori burden enumerations were compared with reference values reported by an expert subspecialist pathologist using a light microscope. Subjective evaluations of image color, brightness, and overall quality were also obtained. There was substantial agreement between the mitotic counts obtained by the evaluating pathologists between monitors and the reference mitotic figure or H pylori burden assessments. Six of the nine evaluating pathologists subjectively evaluated the monitors as substantially similar. These findings are consistent with previous studies demonstrating that color calibration has limited impact on diagnostic accuracy and suggest that noncalibrated displays could be considered for fine assessment tasks.


Impact of Non-pharmacological Chronic Hypertension on a Transgenic Rat Model of Cerebral Amyloid Angiopathy.
Cerebral amyloid angiopathy (CAA), a common comorbidity of Alzheimer's disease (AD), is a cerebral small vessel disease (CSVD) characterized by deposition of fibrillar amyloid β (Aβ) in blood vessels of the brain and promotes neuroinflammation and vascular cognitive impairment and dementia (VCID). Hypertension, a prominent non-amyloidal CSVD, has been found to increase risk of dementia, but clinical data regarding its effects in CAA patients is controversial. To understand the effects of hypertension on CAA, we bred rTg-DI transgenic rats, a model of CAA, with spontaneously hypertensive, stroke prone (SHR-SP) rats producing bigenic rTg-DI/SHR-SP and non-transgenic SHR-SP littermates. At 7 months (M) of age, cohorts of both rTg-DI/SHR-SP and SHR-SP littermates exhibit elevated systolic blood pressures. However, transgene human amyloid β-protein (Aβ) precursor and Aβ peptide levels, as well as behavioral testing showed no changes between bigenic rTg-DI/SHR-SP and rTg-DI rats. Subsequent cohorts of rats were aged further to 10 M where bigenic rTg-DI/SHR-SP and SHR-SP littermates exhibit elevated systolic and diastolic blood pressures. Vascular amyloid load in hippocampus and thalamus was significantly decreased, whereas pial surface vessel amyloid increased, in bigenic rTg-DI/SHR-SP rats compared to rTg-DI rats suggesting a redistribution of vascular amyloid in bigenic animals. There was activation of both astrocytes and microglia in rTg-DI rats and bigenic rTg-DI/SHR-SP rats not observed in SHR-SP rats indicating that glial activation was likely in response to the presence of vascular amyloid. Thalamic microbleeds were present in both rTg-DI rats and bigenic rTg-DI/SHR-SP rats. Although the number of thalamic small vessel occlusions were not different between rTg-DI and bigenic rTg-DI/SHR-SP rats, a significant difference in occlusion size and distribution in the thalamus was found. Proteomic analysis of cortical tissue indicated that bigenic rTg-DI/SHR-SP rats largely adopt features of the rTg-DI rats with enhancement of certain changes. Our findings indicate that at 10 M of age non-pharmacological hypertension in rTg-DI rats causes a redistribution of vascular amyloid and significantly alters the size and distribution of thalamic occluded vessels. In addition, our findings indicate that bigenic rTg-DI/SHR-SP rats provide a non-pharmacological model to further study hypertension and CAA as co-morbidities for CSVD and VCID.


Metagenome-based surveillance and diagnostic approaches to studying the microbial ecology of food production and processing environments.
Metagenomic-based analyses have the potential to revolutionize our understanding of the microbiology of food production and processing environments. By adopting such approaches, it will be possible to more accurately determine sources of microbial contamination, identify critical control points for such contaminants, and select practices that optimize quality and safety. This mini-review will discuss the merits of adopting metagenostic-based approaches, highlight novel insights that they have provided to date and consider how they could be further implemented.


Hepatic tuberculosis: myriad of hues.
Gastrointestinal tuberculosis is an important form of extrapulmonary tuberculosis but liver involvement is uncommon. Hepatic tuberculosis can manifest in variable manners including as a space occupying lesion, diffuse infiltration by granulomas (granulomatous hepatitis) and as liver abscess. Hepatic tuberculosis is usually associated with lesions elsewhere but the diagnosis is often not considered because of rarity. We report two cases of hepatic involvement by tuberculosis: one in the form of liver abscess and the other having multiple hypodense hepatic lesions along with peritoneal involvement. The presence of ascites, visceral scalloping and multiple hypodense lesions resulted in a diagnostic confusion with disseminated malignancy but GeneXpert Ultra (Cepheid, USA) helped in making the diagnosis. Hepatic tuberculosis should be considered in the differential diagnosis of hepatic space occupying lesions and abscesses. This is especially important in TB endemic regions and in patients where there is involvement of other organs especially the lungs. Newer microbiological modalities including GeneXpert Ultra could help in making a diagnosis of hepatic tuberculosis.


Feasibility of intracranial surgery in the rat fetus: model and surgical principles.
The feasibility of intracranial surgery in the rat fetus is demonstrated by the use of a microsurgical model. In utero craniotomy and cerebral incision have been performed successfully without compromise of the fetal-maternal unit. Maternal and fetal survival rates of 95 and 93%, respectively, are reported. Several principles of fetal surgery have been established and are discussed. These include the inhibition of uterine contraction, monitoring of physiological variables, timing of operation, microsurgical technique, and preservation of amniotic fluid. The fetal rat model is amenable to antenatal research because it fulfills certain criteria, including accurately timed pregnancies, littermate controls, inexpensiveness, and animal availability.


Autorepression of the human cytomegalovirus major immediate-early promoter/enhancer at late times of infection is mediated by the recruitment of chromatin remodeling enzymes by IE86.
The human cytomegalovirus major immediate-early protein IE86 is pivotal for coordinated regulation of viral gene expression throughout infection. A relatively promiscuous transactivator of viral early and late gene transcription, IE86 also acts during infection to negatively regulate its own promoter via direct binding to a 14-bp palindromic IE86-binding site, the cis repression sequence (crs), located between the major immediate-early promoter (MIEP) TATA box and the start of transcription. Although such autoregulation does not involve changes in the binding of basal transcription factors to the MIEP in vitro, it does appear to involve selective inhibition of RNA polymerase II recruitment. However, how this occurs is unclear. We show that autorepression by IE86 at late times of infection correlates with changes in chromatin structure around the MIEP during the course of infection and that this is likely to result from physical and functional interactions between IE86 and chromatin remodeling enzymes normally associated with transcriptional repression of cellular promoters. Firstly, we show that IE86-mediated autorepression is inhibited by histone deacetylase inhibitors. We also show that IE86 interacts, in vitro and in vivo, with the histone deacetylase HDAC1 and histone methyltransferases G9a and Suvar(3-9)H1 and that coexpression of these chromatin remodeling enzymes with IE86 increases autorepression of the MIEP. Finally, we show that mutation of the crs in the context of the virus abrogates the transcriptionally repressive chromatin phenotype normally found around the MIEP at late times of infection, suggesting that negative autoregulation by IE86 results, at least in part, from IE86-mediated changes in chromatin structure of the viral MIEP.


Radiomics analysis of contrast-enhanced CT for staging liver fibrosis: an update for image biomarker.
To establish and validate a radiomics-based model for staging liver fibrosis at contrast-enhanced CT images. This retrospective study developed two radiomics-based models (R-score: radiomics signature; R-fibrosis: integrate radiomic and serum variables) in a training cohort of 332 patients (median age, 59 years; interquartile range, 51-67 years; 256 men) with biopsy-proven liver fibrosis who underwent contrast-enhanced CT between January 2017 and December 2020. Radiomic features were extracted from non-contrast, arterial and portal phase CT images and selected using the least absolute shrinkage and selection operator (LASSO) logistic regression to differentiate stage F3-F4 from stage F0-F2. Optimal cutoffs to diagnose significant fibrosis (stage F2-F4), advanced fibrosis (stage F3-F4) and cirrhosis (stage F4) were determined by receiver operating characteristic curve analysis. Diagnostic performance was evaluated by area under the curve, Obuchowski index, calibrations and decision curve analysis. An internal validation was conducted in 111 randomly assigned patients (median age, 58 years; interquartile range, 49-66 years; 89 men). In the validation cohort, R-score and R-fibrosis (Obuchowski index, 0.843 and 0.846, respectively) significantly outperformed aspartate transaminase-to-platelet ratio (APRI) (Obuchowski index, 0.651; p < .001) and fibrosis-4 index (FIB-4) (Obuchowski index, 0.676; p < .001) for staging liver fibrosis. Using the cutoffs, R-fibrosis and R-score had a sensitivity range of 70-87%, specificity range of 71-97%, and accuracy range of 82-86% in diagnosing significant fibrosis, advanced fibrosis and cirrhosis. Radiomic analysis of contrast-enhanced CT images can reach great diagnostic performance of liver fibrosis.


Inability to detect human T cell lymphotropic virus type 2-specific antibodies in a patient coinfected with HIV-1, human T cell lymphotropic virus type 1, human T cell lymphotropic virus type 2, and hepatitis C virus.
HIV-1, human T cell lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) and hepatitis C virus (HCV) are common among intravenous drug users (IDUs) and can cause chronic infections in the host. Usually, the diagnosis of such viruses employs serological assays; however, some difficulties in confirming HTLV-2 infection have been reported in high-risk populations in Brazil. We present data of an unusual case of coinfection with HIV-1, HTLV-1, HTLV-2, and HCV in a male IDU in which HTLV-2 was detected only by molecular assays. Comparative analysis of retroviruses from 2002 and 2012 showed identical HTLV-1 and HTLV-2 sequences (LTR, env, and tax), and a change in HIV-1 tropism from CXCR4 to CCR5. No mutation was detected in the hot points of the env region of the HTLV-2 isolate that justified the lack of rgp46-II-specific antibodies. These data emphasize the need for molecular assays to diagnose HTLV-2 in high-risk populations in Brazil.


Allergies to dental materials.
Allergies related to dentistry generally constitute delayed hypersensitive reactions to specific dental materials. Although true allergic hypersensitivity to dental materials is rare, certain products have definite allergenic properties. Extensive reports in the literature substantiate that certain materials cause allergies in patients, who exhibit mucosal and skin symptoms. Currently, however, neither substantial data nor clinical experience unequivocally contraindicate the discontinuance of any of the materials, which include dental amalgam and nickel- and chromium-containing metals. The dentist forms a vital link in the team approach to the differential diagnosis of allergenic biomaterials that elicit symptoms in a patient, not only intraorally, but also on unrelated parts of the body.


Anastomotic recurrence after curative resection of a transverse colon carcinoma: a case report.
We report a case of anastomotic recurrence after curative surgery for transverse colon cancer in a 53-year-old man. The recurrence was first detected as a submucosal tumor 1.3 cm in diameter, located on the suture line, during an annual follow-up barium enema and colonoscopy. A repeat examination 3 months later showed the lesion to be a typical colon cancer, 2.5 cm in size, with a large ulcerated area. Right hemicolectomy was performed with curative intent. Anastomotic recurrence is much rarer after colonic resection than after anterior resection. This was the first time that we had detected a recurrent lesion as a submucosal tumor during annual follow-up examination.


A retrospective study of risk factors for cardiopulmonary events during propofol-mediated gastrointestinal endoscopy in patients aged over 70 years.
Because of its rapid onset and recovery profile, propofol-mediated sedation is predominantly used during endoscopy. To examine procedure-specific occurrence and risk factors for cardiopulmonary events during propofol-mediated gastrointestinal endoscopy in patients aged over 70 years. Retrospective study with the anesthesia recorder system was performed to determine the occurrence and frequency of cardiopulmonary events. We enrolled 660 elderly outpatients who had undergone gastrointestinal endoscopies in our hospital between May 2006 and May 2007. Multivariate logistic regression analysis was performed using variables, including age, body mass, American Society of Anesthesiologists (ASA) classification, anddifferent anesthetic method either by monitored anesthesia care or intravenously administered propofol, to determine the risks of cardiopulmonary events. Slight adverse effects occurred in 88 patients during gastro-intestinal endoscopy, and no severe cardiopulmonary events occurred. There was no significant correlation between the adverse effects and sex or anesthetic methods (p = 0.95 and p = 0.053, respectively). There was a significant correlation between the occurrence of cardiopulmonary events and both age and body mass (p = 0.022 and p = 0.009, respectively). The procedure-specific risk factors for cardiopulmonary events during propofol-mediated gastrointestinal endoscopy in patients aged over 70 years include age and body mass. These factors should be taken into account during future comparative trials.


Technology scripts in care practice: A case study of assistant nurses' use of a social alarm system in Swedish nursing homes.
Technologies such as social alarm systems contain expectations about how they should be integrated and used in practice. These expectations, also called technology scripts, usually fail to consider all the complexity in care practice. Shifting the focus from technology scripts to care practice, this paper examines how a social alarm system is used in assistant nurses' care practices in nursing homes. The paper draws on observations of assistant nurses' daily tasks (32 h) and semi-structured interviews with assistant nurses (n = 12) in two Swedish nursing homes. The observation data were used to understand the care contexts and assistant nurses' technology-mediated care practices, while interviews were used to deeply understand assistant nurses' perceptions of the system, their care practices, and which aspects they considered during the provision of care. We show the complexities involved in integrating a social alarm system into care practices based on assistant nurses' situational and personal interpretations of both technology scripts and quality of care. The technology-mediated care practices consist of receiving alarms from residents, checking alarms via alarm phones, responding to alarms via alarm phones, checking specific residents' situations in person, documenting all finished alarms, and documenting some finished alarms. In these practices, the assistant nurses defined technology scripts according to their expected requirements and outcomes, and meanwhile considered the quality of care by evaluating the priority of practical, moral or relational care in the situations at hand. Through further negotiations with the defined scripts and the considered quality of care, the assistant nurses decided on the final way of following (or not following) specific scripts in practice. Results from our study portray the complexity of technology in care practices. The findings contribute to increased understanding of technology-mediated care practices in nursing homes, and research on technology scripts in institutional settings.


Antibiotics: A Bibliometric Analysis of Top 100 Classics.
Citation frequencies represent the most significant contributions in any respective field. This bibliometric analysis aimed to identify and analyze the 100 most-cited publications in the field of antibiotics and to highlight the trends of research in this field. "All databases" of Clarivate Analytics' Web of Science was used to identify and analyze the 100 publications. The articles were then cross-matched with Scopus and Google Scholar. The frequency of citation ranged from 940 to 11,051 for the Web of Science, 1053 to 10,740 for Scopus, and 1162 to 20,041 for Google Scholar. A total of 513 authors made contributions to the ranked list, and Robert E.W. Hancock contributed in six articles, which made it to the ranked list. Sixty-six scientific contributions originated from the United States of America. Five publications were linked to the University of Manitoba, Canada, that was identified as the educational organization, made the most contributions (n = 5). According to the methodological design, 26 of the most cited works were review-type closely followed by 23 expert opinions/perspectives. Eight articles were published in Nature journal, making it the journal with the most scientific contribution in this field. Correlation analysis between the publication age and citation frequency was found statistically significant (p = 0.012).


Accurate determination of quantity of material in thin films by Rutherford backscattering spectrometry.
Ion beam analysis (IBA) is a cluster of techniques including Rutherford and non-Rutherford backscattering spectrometry and particle-induced X-ray emission (PIXE). Recently, the ability to treat multiple IBA techniques (including PIXE) self-consistently has been demonstrated. The utility of IBA for accurately depth profiling thin films is critically reviewed. As an important example of IBA, three laboratories have independently measured a silicon sample implanted with a fluence of nominally 5 × 10(15) As/cm(2) at an unprecedented absolute accuracy. Using 1.5 MeV (4)He(+) Rutherford backscattering spectrometry (RBS), each lab has demonstrated a combined standard uncertainty around 1% (coverage factor k = 1) traceable to an Sb-implanted certified reference material through the silicon electronic stopping power. The uncertainty budget shows that this accuracy is dominated by the knowledge of the electronic stopping, but that special care must also be taken to accurately determine the electronic gain of the detection system and other parameters. This RBS method is quite general and can be used routinely to accurately validate ion implanter charge collection systems, to certify SIMS standards, and for other applications. The generality of application of such methods in IBA is emphasized: if RBS and PIXE data are analysed self-consistently then the resulting depth profile inherits the accuracy and depth resolution of RBS and the sensitivity and elemental discrimination of PIXE.


Potent, orally bioavailable diazabicyclic small-molecule mimetics of second mitochondria-derived activator of caspases.
A series of small-molecule Smac mimetics containing a diazabicyclic core structure have been designed, synthesized, and evaluated. The most potent compound (6) binds to XIAP, cIAP-1, and cIAP-2 with K(i) values of 8.4, 1.5, and 4.2 nM, respectively, directly antagonizes XIAP in a cell-free functional assay and induces cIAP-1 degradation in cancer cells. It inhibits cell growth with an IC(50) value of 31 nM, effectively induces apoptosis in the MDA-MB-231 cancer cell line, and has a good oral bioavailability.


Further evidence of the involvement of the c-abl oncogene in chronic myelogenous leukemia and acute lymphocytic leukemia.
In an attempt to further substantiate the involvement of the c-abl oncogene in the genesis of chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL), we performed in-situ hybridization with the c-abl probe on metaphase chromosomes of a healthy control, a karyotypically normal non-CML leukemia, three cases of CML with t(9;22), t(13;22) and t(3;9;22), one blast phase CML with t(9;22), Ph, + Ph, and one ALL with t(9;22), Ph, + Ph. The aberrant 9q could be cytogenetically identified in all cases except t(13;22). The molecular data clearly demonstrated the involvement of the c-abl in t(13;22) and the karyotype was revised to t(9;13;22). All patients, except the control, showed the altered c-able/bcr rearrangement that has been demonstrated in the Ph-chromosome from the standard t(9;22) translocation. These findings suggest that genomic diversities have important clinical differences in these two diseases. The amalgamation of information from cytogenetic and molecular data on cases where translocations are not precise or difficult to identify, will lead towards a deeper understanding of leukemias.


Day by day, hour by hour: Naturalistic language input to infants.
Measurements of infants' quotidian experiences provide critical information about early development. However, the role of sampling methods in providing these measurements is rarely examined. Here we directly compare language input from hour-long video-recordings and daylong audio-recordings within the same group of 44 infants at 6 and 7 months. We compared 12 measures of language quantity and lexical diversity, talker variability, utterance-type, and object presence, finding moderate correlations across recording-types. However, video-recordings generally featured far denser noun input across these measures compared to the daylong audio-recordings, more akin to 'peak' audio hours (though not as high in talkers and word-types). Although audio-recordings captured ~10 times more awake-time than videos, the noun input in them was only 2-4 times greater. Notably, whether we compared videos to daylong audio-recordings or peak audio times, videos featured relatively fewer declaratives and more questions; furthermore, the most common video-recorded nouns were less consistent across families than the top audio-recording nouns were. Thus, hour-long videos and daylong audio-recordings revealed fairly divergent pictures of the language infants hear and learn from in their daily lives. We suggest that short video-recordings provide a dense and somewhat different sample of infants' language experiences, rather than a typical one, and should be used cautiously for extrapolation about common words, talkers, utterance-types, and contexts at larger timescales. If theories of language development are to be held accountable to 'facts on the ground' from observational data, greater care is needed to unpack the ramifications of sampling methods of early language input.


RNase III cleavage of Escherichia coli beta-galactosidase and tryptophan operon mRNA.
Purified RNase III of Escherichia coli cleaved the initial 479-nucleotide sequence of lac operon mRNA at four specific sites and also gave limited cleavage of trp operon mRNA. This action explains the inactivation of mRNA coding capacity by RNase III in vitro.


An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring.
The purpose of this study was to develop a topical matrix metalloproteinase inhibitor preparation for antiscarring therapy. The broad spectrum matrix metalloproteinase inhibitor ilomastat was formulated using 2-hydroxypropyl-β-cyclodextrin in aqueous solution. In vitro activity of ilomastat-cyclodextrin (ilomastat-CD) was examined using fibroblasts seeded in collagen. Permeation of ilomastat-CD eye drop through pig eye conjunctiva was confirmed using Franz diffusion cells. Ilomastat-CD eye drop was applied to rabbit eyes in vivo, and the distribution of ilomastat in ocular tissues and fluids was determined by liquid chromatography-mass spectroscopy. The aqueous solubility of ilomastat-CD was ∼1000 μg/mL in water and 1400 μg/mL in PBS (pH 7.4), which is greater than ilomastat alone (140 and 160 μg/mL in water and PBS, respectively). The in vitro activity of ilomastat-CD to inhibit collagen contraction in the presence of human Tenon fibroblast cells was unchanged compared to uncomplexed ilomastat. Topically administered ilomastat-CD in vivo to rabbit eyes resulted in a therapeutic concentration of ilomastat being present in the sclera and conjunctiva and within the aqueous humor. Ilomastat-CD has the potential to be formulated as an eye drop for use as an antifibrotic, which may have implications for the prevention of scarring in many settings, for example glaucoma filtration surgery.


Reductive dechlorination of DDE to DDMU in marine sediment microcosms.
DDT is reductively dechlorinated to DDD and dehydrochlorinated to DDE; it has been thought that DDE is not degraded further in the environment. Laboratory experiments with DDE-containing marine sediments showed that DDE is dechlorinated to DDMU in both methanogenic and sulfidogenic microcosms and that DDD is dehydrochlorinated to DDMU three orders of magnitude more slowly. Thus, DDD does not appear to be an important precursor of the DDMU found in these sediments. These results imply that remediation decisions and risk assessments based on the recalcitrance of DDE in marine and estuarine sediments should be reevaluated.


A microbiological system for screening the interference of XNA monomers with DNA and RNA metabolism.
We explored the toxicity and mutagenicity of a wide range of xenobiotic nucleoside triphosphates to an Escherichia coli strain equipped with a nucleoside triphosphate transporter. This bacterial test provides a tool to evaluate and guide the synthesis of nucleotides for applications such as the propagation of non-natural genetic information or the selection of potential drugs.


Lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) during primary Epstein-Barr virus (EBV) infection.
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening idiosyncratic drug reaction that may result in skin eruption, mucous membrane involvement, eosinophilia, atypical lymphocytosis and lymphadenopathy, with wide-ranging internal organ involvement. The authors report the case of a 21-year-old man who was prescribed lamotrigine for anxiety disorder. After 2 weeks of treatment, he developed a pruritic morbilliform rash on his trunk and upper extremities that was associated with fever, sore throat, bilateral scleral injection, nausea, vomiting and abdominal pain. A laboratory work-up revealed elevated transaminases and atypical lymphocytosis. He was found to have an active Epstein-Barr virus infection. Lamotrigine was discontinued due to suspicion of DRESS; the patient received pulsed intravenous methylprednisolone followed by oral prednisone taper, which resulted in a significant improvement of symptoms. At follow-up 3 weeks later, signs and symptoms had completely resolved. Follow-up laboratory tests revealed that liver dysfunction had normalised.


Microangiography of end-stage kidneys in relation to high renin hypertension.
Microangiography of end-stage kidneys in relation to high renin hypertension. 15 patients with end-stage renal disease (ESRD) and maintained on chronic hemodialysis were studied with respect to hypertension, the plasma renin activity (PRA) and microangiography of endstage kidneys which were removed for various reasons. The microangiographic patterns were classified into three according to characteristic findings: The first one was characterized by gross dilatation of interlobular arteries and afferent arterioles with poor opacification of efferent and peritubular vessels. This pattern was designated as type 1 (Fig. 1, 2.) Another pattern had total irregularity of renal vascular architectures and differentiation of cortical arteries were impossible. This was classified as type 2 (Fig. 3, 4.) The third one which was grouped as type 3 was characterized by good and fine vascularity of cortical vessels without evidence of obstruction (Fig. 5, 6.) These findings were confirmed by histological studies. All 5 patients with uncontrollable hypertension had type 3 kidneys. Their PRA were abnormally high, but normalized after bilateral nephrectomy. It was suggested that intractable hypertension in patients with ESRD may be an evidence of relatively well preserved cortical circulation despite of extensive parenchymal destruction as seen in type 3 kidneys, in which intensive hemodialysis and ultrafiltration will result in volume depletion, decrease in renal perfusion pressure and excessive renin secretion from the remaining nephrons.


Stability of infants' preference for prosocial others: Implications for research based on single-choice paradigms.
Some research suggests infants display a tendency to judge others' prosocial behavior, and in particular, that infants show a strong preference for prosocial others. For example, data from one frequently cited and well-publicized study showed that, after watching a puppet show with three puppets, 74% of infants chose the puppet that "helped" rather than the puppet that "hindered" a third puppet from attaining its goal. The purpose of the current investigation was to replicate these methods and extend them by including a within-subject measure of infant puppet choice across repeated trials to assess the stability of infants' choice. In the current study, 20 infants viewed a puppet show and chose between two puppets (i.e., helper or hinderer) immediately following the puppet show. Although results were similar to previously published work on the first-choice trial (65% of infants chose the helper puppet on the first trial), infants did not consistently choose the helper across trials; several infants demonstrated a side preference, with 9 infants almost exclusively choosing puppets presented on the right or left side. The current investigation addressed limitations of previous research by including a between-subjects (replication) as well as a within-subjects (extension) repeated measure of choice that allowed for the examination of the stability of the choice measure. Our results, particularly in light of other failed replications, raise questions regarding the robustness of infants' preference for prosocial others and the reliability and validity of the single-choice paradigm.


Stainless steel crowns versus amalgams in the primary dentition and decision-making in clinical practice.
This article reviews scientific dental literature related to amalgam restorations versus stainless steel crowns (SSCs) in the primary dentition. An extensive literature search of clinical studies was conducted to address the use of amalgams and SSCs in the primary dentition. The scientific literature provides evidence that SSCs demonstrate greater longevity and reduced need for retreatment, compared to multi-surface amalgam restorations. There is high-level evidence for the use of SSCs because of their cost-effectiveness, ease of placement, and longevity.


Form of rumen-degradable carbohydrate and nitrogen on microbial protein synthesis and protein efficiency of dairy cows.
Sixteen multiparous lactating Holstein cows (four with rumen cannulae) were fed diets varying in the content and form of ruminally degradable carbohydrates and N to examine dietary effects on microbial protein synthesis (MPS) and whole animal N efficiency, and to evaluate the use of a model based on milk urea N (MUN) for predicting urinary N excretion and N utilization efficiency (NUE). A replicated Latin square design (consisting of diet and experimental period) was employed. The four diets consisted of two low protein diets with either 20% ground corn (diet LP) or 13.5% ground corn plus 3% sucrose (diet LP sucrose) and two high protein diets with 13.5% corn and 3% sucrose with either urea (diet HP urea) or soybean meal (diet HP SBM) as supplemental rumen-degradable protein sources. The intakes of dry matter and N were increased by increasing dietary crude protein (CP) level. However, the yields of milk and milk protein were not affected by CP level. Yield of microbial protein was reduced by sucrose and increased by CP level. There were no differences between urea and SBM supplementation on DM intake, milk yield, or MPS. Mean urinary N excretion for all cows (252 g/d) was underestimated by 55 g/d or overestimated by 25 or 33 g/d using alternative equations based on MUN. Subsequently, NUE (mean = 22.4%) was underestimated by 7.5, 3.2, or 2.9%, using a previously published set of equations. Urinary N excretion and NUE could be predicted within 10 and 14% of observed values, respectively, using a set of equations incorporating MUN. Therefore, MUN appears to be a useful tool to help assess N losses from lactating cows.


Effectiveness of Tong-Xie-Yao-Fang combined with Si-Ni-San for irritable bowel syndrome: A protocol for systematic review and meta-analysis.
Irritable bowel syndrome (IBS) has a high morbidity rate worldwide, but there are no effective treatment measures, which seriously affect people's lives. Previous clinical studies on Tong-Xie-Yao-Fang (TXYF) combined with Si-Ni-San (SNS) in the treatment of IBS have been increasing, but there is no systematic evaluation. This study aims to systematically study the effectiveness of TXYF combined with SNS in the treatment of IBS. The PubMed, EMBASE, Science Network, Cochrane Library, Chinese Biomedical Literature, Wanfang Chinese Digital Journal and Conference Database, China National Knowledge Infrastructure Database and VIP China Science and Technology Journal Database (VIP) will be used Search related literature, and the search time is from the date of establishment to February 2021. The National Institutes of Health clinical registry Clinical Trials, International Clinical Trials Registry Platform and the Chinese clinical trial registration platform will be searched to find ongoing or unpublished trials. After screening the literature according to the criteria, two researchers independently extracted data according to a predetermined table. The primary outcome is total effective rate. The RevMan 5.3.5 software will be used for statistical analysis. Finally, the recommendation, evaluation, development and evaluation system will be used to evaluate the quality evidence for each result. This study will provide the latest evidence of efficacy for the TXYF combined with SNS for IBS. The effectiveness of TXYF combined with SNS for IBS will be evaluated. INPLASY202120075.


Improved and semi-automated reductive β-elimination workflow for higher throughput protein O-glycosylation analysis.
Protein O-glycosylation has shown to be critical for a wide range of biological processes, resulting in an increased interest in studying the alterations in O-glycosylation patterns of biological samples as disease biomarkers as well as for patient stratification and personalized medicine. Given the complexity of O-glycans, often a large number of samples have to be analysed in order to obtain conclusive results. However, most of the O-glycan analysis work done so far has been performed using glycoanalytical technologies that would not be suitable for the analysis of large sample sets, mainly due to limitations in sample throughput and affordability of the methods. Here we report a largely automated system for O-glycan analysis. We adapted reductive β-elimination release of O-glycans to a 96-well plate system and transferred the protocol onto a liquid handling robot. The workflow includes O-glycan release, purification and derivatization through permethylation followed by MALDI-TOF-MS. The method has been validated according to the ICH Q2 (R1) guidelines for the validation of analytical procedures. The semi-automated reductive β-elimination system enabled for the characterization and relative quantitation of O-glycans from commercially available standards. Results of the semi-automated method were in good agreement with the conventional manual in-solution method while even outperforming it in terms of repeatability. Release of O-glycans for 96 samples was achieved within 2.5 hours, and the automated data acquisition on MALDI-TOF-MS took less than 1 minute per sample. This largely automated workflow for O-glycosylation analysis showed to produce rapid, accurate and reliable data, and has the potential to be applied for O-glycan characterization of biological samples, biopharmaceuticals as well as for biomarker discovery.


5-FU and ixabepilone modify the microRNA expression profiles in MDA-MB-453 triple-negative breast cancer cells.
This study aimed to discover new potential mechanisms of chemotherapy with drugs used in the treatment of luminal androgen receptor (LAR)-type triple-negative breast cancer (TNBC). We examined the microRNA (miRNA) expression profiles of LAR-type TNBC in vitro, and explored the variation in miRNA expression profiles in cells when treated with the chemotherapy drugs capecitabine and ixabepilone. The present study revealed that the expression levels of the three antitumor miRNAs, miR-122a, miR-145 and miR-205, were significantly elevated in MDA-MB-453 LAR-type TNBC tumor cells treated with 5-fluorouracil together with ixabepilone. By contrast, carcinogenic miR-296 miRNA expression significantly declined, and levels of several other miRNAs such as miR-221, miR-210, miR-21 and miR-10b were also altered. The drugs may exert their effects through the regulation of miRNA expression levels, thereby providing a theoretical basis for clinical implementation of miRNA expression profiles as a diagnostic method for the early diagnosis, classification and prognosis of breast cancer.


Lower Critical Solution Temperature Phase Transition of Poly(PEGMA) Hydrogel Thin Films.
Surface-attached hydrogel films with well-controlled chemistry are a new approach of polymer thin layers and an actual alternative to polymer brushes and layer-by-layer assemblies. The advantage is that the thickness of hydrogel films can widely range from a few nanometers to several micrometers. Hydrogel films can also remarkably respond to stimuli such as temperature: (i) the thickness change is of great amplitude, fourfold and more, which could not be reached with the geometry of polymer brushes or layer-by-layer assemblies, (ii) the time response is very short (less than 1 s), and (iii) the swelling-to-collapse transition is narrow (a small temperature change of a few degrees may be enough). Poly(N-isopropylacrylamide) (PNIPAM) is the most temperature-responsive polymer investigated with a lower critical solution temperature (LCST) of around 32 °C. However, it is relevant to have the available polymers responding to various transition temperatures with the advantage of keeping the same chemistry. Poly[oligo(ethylene glycol) methacrylate] (PEGMA) meets these specifications since its transition temperature can be finely tuned with the number of oligo ethylene glycol units, while it attractively combines biocompatibility with PEG side chains. Here, we report the synthesis and the temperature-responsive properties of poly(PEGMA) hydrogel thin films. We used a simple, versatile, and well-controlled approach through thiol-ene click reaction, the so-called cross-linking and grafting, to synthesize surface-attached poly(PEGMA) hydrogel films with various thickness. We show that the transition temperature of poly(PEGMA) hydrogel films ranges from 15 to 60 °C if the number of PEG units is from 2 to 5. This transition temperature can also be finely adjusted for hydrogel films containing copolymers or mixing homopolymers of PEGMA with a suitable ratio. Moreover, the LCST properties, swelling-to-collapse amplitude and transition temperature, are not sensitive to salt. In particular, there is no effect on the LCST properties of surface-attached poly(PEGMA) hydrogel films in phosphate saline buffer, which is promising for applications in biology such as injectable hydrogels, drug delivery systems, hydrogel-based microfluidic valves, and flow switches for biotechnologies.


Signal transduction in podocytes--spotlight on receptor tyrosine kinases.
The mammalian kidney filtration barrier is a complex multicellular, multicomponent structure that maintains homeostasis by regulating electrolytes, acid-base balance, and blood pressure (via maintenance of salt and water balance). To perform these multiple functions, podocytes--an important component of the filtration apparatus--must process a series of intercellular signals. Integrating these signals with diverse cellular responses enables a coordinated response to various conditions. Although mature podocytes are terminally differentiated and cannot proliferate, they are able to respond to growth factors. It is possible that the initial response of podocytes to growth factors is beneficial and protective, and might include the induction of hypertrophic cell growth. However, extended and/or uncontrolled growth factor signalling might be maladaptive and could result in the induction of apoptosis and podocyte loss. Growth factors signal via the activation of receptor tyrosine kinases (RTKs) on their target cells and around a quarter of the 58 RTK family members that are encoded in the human genome have been identified in podocytes. Pharmacological inhibitors of many RTKs exist and are currently used in experimental and clinical cancer therapy. The identification of pathological RTK-mediated signal transduction pathways in podocytes could provide a starting point for the development of novel therapies for glomerular disorders.


Eptifibatide-induced acute profound thrombocytopenia: A case report.
Eptifibatide is an antiplatelet agent used in the medical management of acute coronary syndrome. Although multiple studies did not reveal a significant association between eptifibatide and the development of thrombocytopenia, recent case reports brought attention to this relatively rare side effect. We report a 61 years old male with acute coronary syndrome who underwent primary coronary intervention. The patient developed acute profound thrombocytopenia following eptifibatide administration. Following prompt offending drug discontinuation, the platelet counts recovered, without clinical sequelae or the need for platelet transfusion. Dual antiplatelet therapy with aspirin and clopidogrel was resumed after platelet count normalization. The patient had a normal platelet count and no bleeding events on follow-up after three months upon discharge. Eptifibatide, a glycoprotein IIa/IIIb inhibitor used in the management of acute coronary syndrome, can induce acute, profound thrombocytopenia that can have significant morbidity in patients. This case highlights this relatively rare side effect and the importance of monitoring blood counts and observing for any signs of bleeding or thrombosis that might occur in such patients.


Work-Related Asthma Among Certified Nurse Aides in Texas.
Background: Although nurses are well described as being at risk of work-related asthma, certified nurse aides (CNAs) are understudied. Using a statewide registry in Texas, we measured prevalence and risk factors for work-related asthma and bronchial hyperresponsiveness (BHR) symptoms among CNAs. Methods: For this cross-sectional study, a questionnaire was mailed to a random sample of CNAs (n = 2,114) identified through the Texas Department of Aging and Disability Services registry, working in health care during 2016-2017, to collect data on job history, asthma symptoms, and sociodemographics. Two outcomes were defined: (a) new-onset asthma (NOA) after entry into the health care field and (b) BHR-related symptoms. Job exposures to cleaning compounds and tasks were assigned using an externally coded CNA-specific job-exposure matrix. Logistic regression modeling was used to measure associations between cleaning exposures and the two asthma outcomes. Findings: The final sample consisted of 413 CNAs (response rate 21.6%). The prevalence of NOA and BHR symptoms were 3.6% and 26.9%, respectively. In adjusted models, elevated odds for BHR symptoms were observed for patient care cleaning (odds ratio [OR] = 1.71, 95% confidence interval [CI] = [0.45, 6.51]), instrument cleaning (OR = 1.33, 95% CI = [0.66, 2.68]), building-surface cleaning (OR = 1.39, 95% CI = [0.35, 5.60]), exposure to glutaraldehyde/orthophthalaldehyde (OR = 1.33, 95% CI = [0.66, 2.68]), and latex glove use during 1992-2000 (OR = 1.62, 95% CI = [0.84, 3.12]). There were too few NOA cases to warrant meaningful regression analysis. Conclusion/Application to Practice: Although not statistically significant, we observed elevated odds of BHR symptoms among nurse aides, associated with cleaning exposures, suggesting this is an at-risk group of health care professionals for work-related respiratory disease, meriting further study.


Subungual Melanoma In Situ Treated With Imiquimod 5% Cream After Conservative Surgery Recurrence.

Subungual melanoma is a rare variant of acral lentiginous melanoma that often has a poor prognosis compared with other types of melanoma. The aim of the present study is to report a case of a patient with recurrence of subungual melanoma treated with imiquimod 5%, which presented a total regression of the lesion and no recurrence for 4 years.

J Drugs Dermatol. 2017;16(3):268-270.
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Copper nanowires as nanofertilizers for alfalfa plants: Understanding nano-bio systems interactions from microbial genomics, plant molecular responses and spectroscopic studies.
The recent application of nano copper (Cu) compounds in the agrosystem has shown potential to improve the physiological performance and agronomical parameters of crops. We grew alfalfa (Medicago sativa) in potting mix amended with bulk, nano, and ionic Cu compounds at 80 and 280 mg Cu/kg; then, we evaluated plant performance at physiological and molecular levels. Plants treated with bulk/nano Cu presented better agronomical responses. The P and S content was reduced in bulk and ionic Cu-exposed plants, compared to controls (p ≤ .05). All Cu forms increased the content of Fe and Zn in roots and Fe in leaves, compared to controls (p ≤ .05). Leaf-superoxide dismutase expression was augmented ~27-fold and rubisco mRNA was unaffected in bulk/nano Cu-treated plants, compared to controls (p ≤ .05). Bulk/nano Cu incremented the relative abundance of microorganisms involved in the elemental uptake. These results indicate that nano Cu improved the physiology of alfalfa and can be considered as potential nanofertilizers.


Disease characteristics and clinical outcome in young adults with essential thrombocythemia versus early/prefibrotic primary myelofibrosis.
In the present study, we investigated disease characteristics and clinical outcome in young patients (< 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) compared with early/prefibrotic primary myelofibrosis (PMF) with presenting thrombocythemia. We recruited 213 young patients (median age, 33.6 years), including 178 patients (84%) with WHO-defined ET and 35 patients (16%) showing early PMF. Median follow-up time was 7.5 years. A trend for more overall thrombotic complications, particularly arterial, was seen in early PMF compared with ET. Progression to overt myelofibrosis was 3% in ET and 9% in early PMF, but no transformation into acute leukemia was observed. Combining all adverse events (thrombosis, bleeding, and myelofibrosis), the rate was significantly different (1.29% vs 3.43% of patients/year, P = .01) in WHO-ET and early PMF, respectively. In multivariate analysis, early PMF and the JAK2V617F mutation emerged as independent factors predicting cumulative adverse events.


Tenderness, climate, and citrus fruit.
Tenderness of coastal-grown citrus fruit to fumigation, spray, and storage practices, and to frost, as compared with fruit grown in the drier interior districts of southern California, is correlated with lower puncture-pressures and higher moisture content of peel. The hardening effect of moisture stress is also exhibited by fruit from tree tops.


[Acyclovir in herpes neonatorum].
In case of vaginal delivery herpes genitalis of pregnant women is the main reason for infection of the new-born. According to Anne Yeager, 2.4% of pregnant women with a past history if HSV infections are asymptomatically shedding herpes viruses at term without manifestation of a herpes infection of the new-born in most cases. The reasons for this could be: a sufficient antibody titre of the new-born (diaplacental transmission of maternal antibodies; term infant. According to Whitley the morbidity is about 1 to 5 infections per 10,000 deliveries; 50% of the infected infants do not show any cutaneous efflorescences and could therefore be wrong diagnosed.


Cochlear implantation in children with keratitis-ichthyosis-deafness (KID) syndrome: outcomes in three cases.
Three children with keratitis-ichthyosis-deafness (KID) syndrome received cochlear implants at the Royal Victorian Eye and Ear Hospital. KID syndrome is a rare genodermatosis associated with mutation of the connexin-26 gene with characteristics affecting skin, hair, vision and hearing. Ichthyotic involvement of the ear canal epithelium and associated non-erosive keratosis obturans complicate hearing assessment and aid fitting. The tendency to eczematous dermatitis and otitis media is an additional problem with cochlear implantation. All cases have required additional medical management, however the outcomes show that the cochlear implant can be effective in these patients.


Stroke-Specific Predictors of Major Bleeding in Anticoagulated Patients With Stroke and Atrial Fibrillation: A Nationwide Multicenter Registry-Based Study.
The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs). Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival. Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050). This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.


Plant growth retardation and conserved miRNAs are correlated to Hibiscus chlorotic ringspot virus infection.
Virus infection may cause a multiplicity of symptoms in their host including discoloration, distortion and growth retardation. Hibiscus chlorotic ringspot virus (HCRSV) infection was studied using kenaf (Hibiscus cannabinus L.), a non-wood fiber-producing crop in this study. Infection by HCRSV reduced the fiber yield and concomitant economic value of kenaf. We investigated kenaf growth retardation and fluctuations of four selected miRNAs after HCRSV infection. Vegetative growth (including plant height, leaf size and root development) was severely retarded. From the transverse and radial sections of the mock and HCRSV-infected kenaf stem, the vascular bundles of HCRSV-infected plants were severely disrupted. In addition, four conserved plant developmental and defence related microRNAs (miRNAs) (miR165, miR167, miR168 and miR171) and their respective target genes phabulosa (PHB), auxin response factor 8 (ARF8), argonaute 1 (AGO1) and scarecrow-like protein 1 (SCL1) displayed variation in expression levels after HCRSV infection. Compared with the mock inoculated kenaf plants, miR171 and miR168 and their targets SCL1 and AGO1 showed greater fluctuations after HCRSV infection. As HCRSV upregulates plant SO transcript in kenaf and upregulated AGO1 in HCRSV-infected plants, the expression level of AGO1 transcript was further investigated under sulfite oxidase (SO) overexpression or silencing condition. Interestingly, the four selected miRNAs were also up- or down-regulated upon overexpression or silencing of SO. Plant growth retardation and fluctuation of four conserved miRNAs are correlated to HCRSV infection.


Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.
Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells.


Rapid analysis of forensic-related samples using two ambient ionization techniques coupled to high-resolution mass spectrometers.
This paper highlights the versatility of interfacing two ambient ionization techniques, Laser Diode Thermal Desorption (LDTD) and Atmospheric Solids Analysis Probe (ASAP), to high-resolution mass spectrometers and demonstrate the method's capability to rapidly generate high-quality data from multiple sample types with minimal, if any, sample preparation. For ASAP-MS analysis of solid and liquid samples, the material was transferred to a capillary surface before being introduced into the mass spectrometer. For LDTD-MS analysis, samples were solvent extracted, spotted in a 96-well plate, and the solvent was evaporated before being introduced into the mass spectrometer. All analyses were performed using Atmospheric Pressure Chemical Ionization in positive mode. Seven consumer "Spice" packets were combined and analyzed by both ASAP and LDTD, which identified 11 synthetic cannabinoids/cathinones by full MS and MS/MS experiments. To further show the usefulness of these techniques, black tar heroin was analyzed, which resulted in the identification of heroin and its impurities (monoacetylmorphine, papaverine, and noscapine). These experiments were performed on the LTQ-Orbitrap to demonstrate the ability to perform both parallel and serial MS and MSn experiments. Interfacing LDTD and ASAP to high-resolution mass spectrometers allows for expeditious analysis of a wide range of samples, with minimal or no sample preparation. Both allow for rapid full scan, MS/MS, and/or MSn experiments from a single sample introduction. Published in 2017. This article is a U.S. Government work and is in the public domain in the USA.


Reaction kinetics in biofilms.
A novel in situ microtechnique allows evaluating parameters of diffusion-controlled reactions in biofilms. A microprobe, 15 mum in diameter, was used to simultaneously measure the dissolved oxygen concentration and the optical density at different depths in a submerged biofilm. Based on the results, the biofilm diffusion coefficient for dissolved oxygen, D(f) the dissolved oxygen flux through the biofilm surface, J(02), and the half velocity coefficient, K(s), have been calculated.


Platinum-Catalyzed, Terminal-Selective C(sp(3))-H Oxidation of Aliphatic Amines.
This Communication describes the terminal-selective, Pt-catalyzed C(sp(3))-H oxidation of aliphatic amines without the requirement for directing groups. CuCl2 is employed as a stoichiometric oxidant, and the reactions proceed in high yield at Pt loadings as low as 1 mol%. These transformations are conducted in the presence of sulfuric acid, which reacts with the amine substrates in situ to form ammonium salts. We propose that protonation of the amine serves at least three important roles: (i) it renders the substrates soluble in the aqueous reaction medium; (ii) it limits binding of the amine nitrogen to Pt or Cu; and (iii) it electronically deactivates the C-H bonds proximal to the nitrogen center. We demonstrate that this strategy is effective for the terminal-selective C(sp(3))-H oxidation of a variety of primary, secondary, and tertiary amines.


Resonant photoluminescence studies of carrier localisation in c-plane InGaN/GaN quantum well structures.
In this paper we report on changes in the form of the low temperature (12 K) photoluminescence spectra of an InGaN/GaN quantum well structure as a function of excitation photon energy. As the photon energy is progressively reduced we observe at a critical energy a change in the form of the spectra from one which is determined by the occupation of the complete distribution of hole localisation centres to one which is determined by the resonant excitation of specific localisation sites. This change is governed by an effective mobility edge whereby the photo-excited holes remain localised at their initial energy and are prevented from scattering to other localisation sites. This assignment is confirmed by the results of atomistic tight binding calculations which show that the wave function overlap of the lowest lying localised holes with other hole states is low compared with the overlap of higher lying hole states with other higher lying hole states.


Stability of Extemporaneously Prepared Hydroxycarbamide Oral Suspensions.
Hydroxycarbamide, available as tablets, is a pharmacological agent for fetal hemoglobin induction such as sickle cell anemia. The need for alternative dosage form options for patients unable to take tablets led hospital pharmacies to prepare solutions and suspensions. The objective of this study was to determine the stability of hydroxycarbamide in Ora-Plus in combination with either Ora-Sweet or Ora-Sweet SF, Ora-Blend, or Ora-Blend SF suspending agents. The studied samples were compounded into 100-mg/mL suspensions and stored in 60-mL amber glass bottles at room (22°C to 25°C) or refrigerated (4°C to 8°C) temperature. Samples were assayed at each time point out to 120 days by a stability-indicating high-performance liquid chromatography method. The samples were examined for any change in color, odor, visual microbiology, and pH on initial and final day of analysis. At least 90% of hydroxycarbamide concentration remained in all suspensions at the end of the 120-day study period in both conditions. There was no appreciable change in color, odor, or taste. The pH values of suspensions stored at 25°C changed by at least 1 unit at the end of the study period. Based on the data collected, the beyond-use date of these suspensions is 120 days when stored in 60-mL amber glass bottles at both temperature storage conditions.


Stereospecific Winding of Polycyclic Aromatic Hydrocarbons into Trinacria Propellers.
The stereospecific trimerization of enantiomerically pure binaphthols with hexakis(bromomethyl)benzene gives access in one step to enantiomerically pure molecular propellers, in which three binaphthyl rings are held together with dioxecine rings. X-ray diffraction analysis revealed that three out the six naphthyl moieties are folded in a (EF)3 -type arrangement held by three intramolecular C-H⋅⋅⋅π interactions. This slips outward the three remaining naphthyl rings in a blade-like fashion, just like in three-folded propeller components. This peculiar conformation shows striking similarity to the mythological Sicilian symbol of Trinacria, from which the name "trinacria propeller" derives. The propeller conformation is also preserved in chlorinated solutions, as displayed by the presence of a peak at 4.7 ppm typical of an aromatic proton resonance engaged in a C-H⋅⋅⋅π interaction. The denaturation of the propeller-like conformation is obtained at high temperature, corresponding to activation energy for the ring inversion of ca. 18.2 kcal mol-1 . Notably, halide-functionalized molecular propellers exposing I-atoms at the leading and trailing edges could be prepared stereo- and regiospecifically by choosing the relevant iodo-bearing BINOL derivative.


Nanofibrous polymeric beads from aramid fibers for efficient bilirubin removal.
Polymer based hemoperfusion has been developed as an effective therapy to remove the extra bilirubin from patients. However, the currently applied materials suffer from either low removal efficiency or poor blood compatibility. In this study, we report the development of a new class of nanofibrous absorbent that exhibited high bilirubin removal efficiency and good blood compatibility. The Kevlar nanofiber was prepared by dissolving micron-sized Kevlar fiber in proper solvent, and the beads were prepared by dropping Kevlar nanofiber solutions into ethanol. Owing to the nanofiborous structure of the Kevlar nanofiber, the beads displayed porous structures and large specific areas, which would facilitate the adsorption of toxins. In the adsorption test, it was noticed that the beads possessed an adsorption capacity higher than 40 mg g(-1) towards bilirubin. In plasma mimetic solutions, the beads still showed high bilirubin removal efficiency. Furthermore, after incorporating with carbon nanotubes, the beads were found to have increased adsorption capacity for human degradation waste. Moreover, the beads showed excellent blood compatibility in terms of a low hemolysis ratio, prolonged clotting times, suppressed coagulant activation, limited platelet activation, and inhibited blood related inflammatory activation. Additionally, the beads showed good compatibility with endothelial cells. In general, the Kevlar nanofiber beads, which integrated with high adsorption capacity, good blood compatibility and low cytotoxicity, may have great potential for hemoperfusion and some other applications in biomedical fields.


Vaccination equally enables both genetically susceptible and resistant mice to control infection with group A streptococci.
There is substantial evidence that host genetic factors are important in determining susceptibility to infection with group A streptococci (GAS). Several studies have revealed that, similarly to humans, a genetic component may be important in determining susceptibility to GAS infection in mice. Thus, C3H/HeN mice are much more susceptible to streptococcal infection than BALB/c mice. We have determined here whether vaccination makes genetically susceptible mice as capable as genetically resistant mice to control GAS infection. Resistant BALB/c and susceptible C3H/HeN mice were immunized either systemically with heat-killed GAS or through the mucosal route with an M protein-based subunit vaccine, and challenged with live bacteria. Vaccination elicited in both mouse strains similar levels of bactericidal anti-GAS IgG antibodies and also antigen-specific mucosal IgA. Vaccination provided mice of both strains with an increased and equal capacity to express immunity against GAS as indicated by the reduced level of bacteria in the organs and the ability of vaccinated mice to survive infection. Protection in vaccinated mice was dependent on the presence of T cell-dependent bactericidal antibodies as shown by the ability of serum elicited in immunocompetent mice but not of serum elicited in T cell-deficient nu/nu mice to passively transfer anti-GAS immunity. In conclusion, the results presented here demonstrated that the presence of anti-GAS specific, T cell-dependent bactericidal antibodies elicited after vaccination overcomes the innate genetic susceptibility of C3H/HeN mice and makes both resistant and susceptible mice equally capable of controlling GAS infection.