Entirely subcutaneous defibrillator and complex congenital heart disease: Data on long-term clinical follow-up.
To describe the long-term follow-up of patients with complex congenital heart disease who underwent subcutaneous implantable cardiac defibrillator (S-ICD), focusing on local complications, appropriate and inappropriate shocks. Patients with complex congenital heart disease underwent S-ICD implant in two centers with the conventional technique. Data at follow-up were retrieved from clinical notes and institutional database. Eight patients were implanted in two centres between 2010 and 2016. Median age at implant was 37.5 years (range 13-57). All patients who were deemed suitable for S-ICD implant passed the pre-procedural screening. Three patients were previously implanted with a anti-bradycardia device, one of whom with CRT. In one patient the device was explanted due to local infection. During the total median follow-up of 874 d, one patient had an appropriate and one inappropriate shock triggered by fast atrial tachycardia. None of the patients had inappropriate shocks secondary to T wave oversensing or electrical interference with anti- bradycardia devices. S-ICD appears to be effective and safe in patients with complex congenital heart disease.


An open conformation of mammalian cytochrome P450 2B4 at 1.6-A resolution.
The xenobiotic metabolizing cytochromes P450 (P450s) are among the most versatile biological catalysts known, but knowledge of the structural basis for their broad substrate specificity has been limited. P450 2B4 has been frequently used as an experimental model for biochemical and biophysical studies of these membrane proteins. A 1.6-A crystal structure of P450 2B4 reveals a large open cleft that extends from the protein surface directly to the heme iron between the alpha-helical and beta-sheet domains without perturbing the overall P450 fold. This cleft is primarily formed by helices B' to C and F to G. The conformation of these regions is dramatically different from that of the other structurally defined mammalian P450, 2C5/3LVdH, in which the F to G and B' to C regions encapsulate one side of the active site to produce a closed form of the enzyme. The open conformation of 2B4 is trapped by reversible formation of a homodimer in which the residues between helices F and G of one molecule partially fill the open cleft of a symmetry-related molecule, and an intermolecular coordinate bond occurs between H226 and the heme iron. This dimer is observed both in solution and in the crystal. Differences between the structures of 2C5 and 2B4 suggest that defined regions of xenobiotic metabolizing P450s may adopt a substantial range of energetically accessible conformations without perturbing the overall fold. This conformational flexibility is likely to facilitate substrate access, metabolic versatility, and product egress.


Hexahedral mesh generation via constrained quadrilateralization.
Decomposing a volume into high-quality hexahedral cells is a challenging task in finite element simulations and computer graphics. Inspired by the use of a spatial twist continuum and frame field in previous hexahedral mesh generation methods, we present a method of hexahedral mesh generation via constrained quadrilateralization that combines a spatial twist continuum and frame fields. Given a volume represented by a tetrahedral mesh, surface quadrilateral mesh and frame field, we first extend the loop of the surface of a solid to a layer of hexahedral elements, then divide the solid into two smaller sub-solids by the layer, and finally handle them recursively until all of the sub-solids are empty. In our hexahedral mesh generation framework, we apply constrained quadrilateralization to extend the loop to a layer of hexahedral elements. The "divide-and-conquer" strategy used in this method is suitable for parallelization. This method can potentially lead to easier and more robust implementations that are more parallelizable and less dependent on heavy numerical libraries. The testing results show that the quality of the meshes generated by this method is similar to those produced by current state-of-the-art mesh generation methods.


Characterization of primary ovarian cancer cells in different culture systems.
The concept of cancer stem cells (CSCs) provides a new paradigm for understanding cancer biology. Here we report how culture conditions affect the characteristics of primary ovarian cancer cells. Cancer cells disaggregated from ovarian serous adenocarcinoma and maintained in serum-free system culture formed sphere cells that exhibited several properties expected for CSCs. These include self-renewal, overexpression of stemness genes as detected by QPCR analysis, greater tumorigenicity and enhanced drug resistance. The serum-free culture system enriched the percentage of CD133+/CD117+ expressing cells in sphere cells as determined by flow cytometric analysis, immunostaining and Western blot analysis. A cDNA microarray showed that there were 2111 genes exhibiting more than a 2-fold difference in expression. Subsequent ontological analysis revealed that a large proportion of the classified genes were related to cell communication, cell-cell adhesion, cellular development and extracellular matrix. We suggest that the sphere cell subpopulation may be a more reliable model than differentiated cells grown in the presence of serum for understanding the biology of primary ovarian cancer.


Inference on chains of disease progression based on disease networks.
Disease progression originates from the concept that an individual disease may go through different changes as it evolves, and such changes can cause new diseases. It is important to find a progression between diseases since knowing the prior-posterior relationship beforehand can prevent further complications or evolutions to other diseases. Furthermore, the series of progressions can be represented in the form of a chain, which enables us to readily infer successive influences from one disease to another after many passages through other diseases. In this paper, we propose a systematic approach for finding a disease progression chain from a source disease to a target one via exploring a disease network. The network is constructed based on various sets of biomedical data. To find the most influential progression chains, the k-shortest path search algorithm is employed. The most representative algorithms such as A*, Dijkstra, and Yen's are incorporated into the proposed method. A disease network consisting of 3,302 diseases was constructed based on four sources of biomedical data: disease-protein relations, biological pathways, clinical history, and biomedical literature information. The last three sets of data contain prior-posterior information, and they endow directionality on the edges of the network. The results were interesting and informative: for example, when colitis and respiratory insufficiency were set as a source disease and a target one, respectively, five progression chains were found within several seconds (when k = 5). Each chain was provided with a progression score, which indicates the strength of plausibility relative to others. Similarly, the proposed method can be expanded to any pair of source-target diseases in the network. This can be utilized as a preliminary tool for inferring complications or progressions between diseases.


A Chlorella virus gene promoter functions as a strong promoter both in plants and bacteria.
An upstream region from an algal virus methyltransferase gene was tested for promoter function in transgenic plants, electroporated monocot protoplasts and bacteria. Fusion of the 851 bp upstream region to a reporter gene significantly enhanced the reporter gene expression in transgenic Arabidopsis and potato plants and in electroporated maize and Sorghum cells relative to the cauliflower mosaic virus 35S promoter. The promoter was also functional in several Escherichia coli strains and in three species of phytopathogenic bacteria, Erwinia, Pseudomonas, and Xanthomonas. These findings indicate that the upstream region is a strong promoter uniquely functional in both eukaryotes and prokaryotes and capable of using both eukaryotic RNA polymerase II and bacterial RNA polymerases.


The unity and diversity of executive functions: A network approach to life span development.
As a novel approach to conceptualizing executive functions, this study applied network analysis to a common battery of executive function tests administered to a sample covering the life span. Participants (N = 3,944; age: M = 20.8 years, SD = 19.6, range: 3-85; maternal/self education: M = 12.9 years, SD = 2.6; 53.3% girls/women, 46.7% boys/men; 61.1% White, 18.2% African American, 14.0% Latinx, 6.8% other races/ethnicities) completed tests of inhibition, shifting, and updating/working memory. Zero-order and partial correlation network models were calculated for divided age groups, with network parameters compared between groups: edge weights, corresponding to zero-order or partial correlations between two executive functions; expected influence, quantifying centrality; and global strength, quantifying differentiation. Executive functions differentiated from childhood to adolescence and dedifferentiated during young adulthood, with further dedifferentiation at older adulthood. Shifting emerged as more central than other abilities in adolescence and adulthood versus childhood, with a mediational role of shifting between inhibition and updating/working memory. A network approach can appropriately capture the unity and diversity of executive functions, by which unity reflects the reciprocal engagement between diverse abilities to produce goal-directed behavior. The engagement between abilities, and a mediational role of shifting between inhibition and updating/working memory, may be necessary for the emergence of effective goal-directed behavior. Through a network approach, the unity of executive functions represents an emergent property of the dynamics between multiple abilities (e.g., inhibition, shifting, and updating/working memory) that, when working effectively in tandem, lead to integrative processes (e.g., problem solving) that contribute to successful executive behavior and goal attainment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Facile fabrication of a vanadium nitride/carbon fiber composite for half/full sodium-ion and potassium-ion batteries with long-term cycling performance.
Vanadium-based composite anodes have been designed for applications in alkali metal ion batteries, including lithium-ion batteries (LIBs), sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs). However, the problems of inferior long-term cycling stability caused by the large volume change and dissolution of vanadium-based active materials during cycles and slow diffusion for large radii of Na+ and K+ still limit their underlying capability and need to be addressed. In the present work, we initially designed and fabricated a vanadium nitride/carbon fiber (VN/CNF) composite via a facile electrospinning method followed by the ammonization process. The obtained VN/CNF composite anode exhibited excellent half/full sodium and potassium storage performance. When used as an anode material for SIBs, it delivered a high capacity of 403 mA h g-1 at 0.1 A g-1 after 100 cycles and as large as 237 mA h g-1 at 2 A g-1 even after 4000 cycles with negligible capacity fading. More importantly, the VN/CNFs//Na3V2(PO4)3 full cell by coupling the VN/CNF composite anode with the Na3V2(PO4)3 (NVP) cathode also exhibited a desirable capacity of 257 mA h g-1 at 500 mA g-1 after 50 cycles. Besides, when further evaluated as an anode for PIBs, the VN/CNF composite anode achieved a large capacity of 266 mA h g-1 after 200 cycles at 0.1 A g-1 and maintained a stable capacity of 152 mA h g-1 at 1 A g-1 even after 1000 cycles, showing significant long-term cycling stability. This is one of the best performances of vanadium-based anode materials for SIBs and PIBs reported so far.


A polymerase chain reaction assay for the detection of Brugia malayi in blood.
There is need for sensitive, rapid, species-specific diagnosis of Brugia filarial parasites because traditional methods are tedious and time-consuming, with little guarantee of species specificity. A polymerase chain reaction (PCR)-based assay was developed using the Hha I family of highly repeated DNA sequences from Brugia. The assay was tested on 124 human blood samples collected in a field study in Indonesia. These included 66 microfilaria-positive samples from patients in an area endemic for Brugia, 30 from healthy individuals from the same endemic area, and 28 from healthy individuals from a nonendemic area. Twenty-eight blood samples collected in a village in French Polynesia endemic for Wuchereria bancrofti, but not B. malayi, were also tested. The blood samples were screened using the traditional blood smear and membrane filtration methods, which served as the gold standards to which the PCR assay was compared. The samples were digested with proteinase K, extracted with phenol and chloroform, and dialyzed. A fraction of the dialyzed product was used in PCRs using Hha I-specific primers. The PCR assay correctly identified all of the microfilaria-positive samples as PCR positive and all of the nonendemic samples as PCR negative. Additionally, 26 of 30 samples from healthy individuals in the endemic area were also identified as PCR negative, while four were PCR positive. It is likely that these four individuals had very low-level or cryptic infections, and that the PCR assay detected circulating DNA released from dead filariae. The results indicate that the Hha I PCR detection system is rapid, species-specific, and sensitive.


Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo.
Streptococcus (S.) pneumoniae strains vary considerably in their ability to cause invasive disease in humans, which is at least in part determined by the capsular serotype. Platelets have been implicated as sentinel cells in the circulation for host defence. One of their utensils for this function is the expression of Toll-like receptors (TLRs). We here aimed to investigate platelet response to S. pneumoniae and a role for TLRs herein. Platelets were stimulated using four serotypes of S. pneumonia including an unencapsulated mutant strain. In vitro aggregation and flow cytometry assays were performed using blood of healthy volunteers, or blood of TLR knock out and WT mice. For in vivo pneumonia experiments, platelet specific Myd88 knockout (Plt-Myd88-/-) mice were used. We found that platelet aggregation was induced by unencapsulated S. pneumoniae only. Whole blood incubation with all S. pneumoniae serotypes tested resulted in platelet degranulation and platelet-leukocyte complex formation. Platelet activation was TLR independent, as responses were not inhibited by TLR blocking antibodies, not induced by TLR agonists and were equally induced in wild-type and Tlr2-/-, Tlr4-/-, Tlr2/4-/-, Tlr9-/- and Myd88-/- blood. Plt-Myd88-/- and control mice displayed no differences in bacterial clearance or immune response to pneumonia by unencapsulated S. pneumoniae. In conclusion, S. pneumoniae activates platelets through a TLR-independent mechanism that is impeded by the bacterial capsule. Additionally, platelet MyD88-dependent TLR signalling is not involved in host defence to unencapsulated S. pneumoniae in vivo.


Bridging the gap between cadaveric and in vivo experiments: a biomechanical model evaluating thumb-tip endpoint forces.
The thumb is required for a majority of tasks of daily living. Biomechanical modeling is a valuable tool, with the potential to help us bridge the gap between our understanding of the mechanical actions of individual thumb muscles, derived from anatomical cadaveric experiments, and our understanding of how force is produced by the coordination of all of the thumb muscles, derived from studies involving human subjects. However, current biomechanical models do not replicate muscle force production at the thumb-tip. We hypothesized that accurate representations of the axes of rotation of the thumb joints were necessary to simulate the magnitude of endpoint forces produced by human subjects. We augmented a musculoskeletal model with axes of rotation derived from experimental measurements (Holzbaur et al., 2005) by defining muscle-tendon paths and maximum isometric force-generating capacity for the five intrinsic muscles. We then evaluated if this augmented model replicated a broad range of experimental data from the literature and identified which parameters most influenced model performance. The simulated endpoint forces generated by the combined action of all thumb muscles in our model yielded comparable forces in magnitude to those produced by nonimpaired subjects. A series of 8 sets of Monte Carlo simulations demonstrated that the difference in the axes of rotation of the thumb joints between studies best explains the improved performance of our model relative to previous work. In addition, we demonstrate that the endpoint forces produced by individual muscles cannot be replicated with existing experimental data describing muscle moment arms.


Acute toxicity of lead, steel, and an iron-tungsten-nickel shot to mallard ducks (Anas platyrhynchos).
Twenty mallards (Anas platyrhynchos) of both sexes were dosed by oral gavage with Heavi-Shot (H-S; Environ-Metal, Inc., Sweet Home, Oregon, USA) pellets, 20 with steel shot, and 10 with lead (Pb) pellets, all of equal size. All pellets were fired from a shotgun into an absorbent material, retrieved, and weighed prior to introduction into the ducks. Birds were fed whole kernel corn and grit and observed for signs of toxicity for 30 days following dosing. Hevi-Shot pellets lost an average of 6.2% of their mass and steel shot pellets lost 57% of their mass in the birds' gizzards. Almost all (90%) of the Pb shot dosed birds died before the end of the study, while no mortality was observed in the steel or H-S dosed groups. Even though total food consumption differed between the H-S and steel shot groups, mean bird weight change was not different. There were no significant morphologic or histopathologic abnormalities of the liver and kidney in the H-S and steel shot groups. Results indicated that mallards dosed orally with eight No. 4 H-S pellets were not adversely affected over a 30-day period, and that H-S provides another environmentally safe nontoxic shot for use in waterfowl hunting.


Identification of a novel site within G protein alpha subunits important for specificity of receptor-G protein interaction.
Several domains of G protein alpha subunits are implicated in the control of receptor-G protein coupling specificity. Among these are the extreme N-and C-termini, the alpha4/beta6-loops, and the loop linking the N-terminal alpha-helix to the beta1-strand of the ras-like domain. In this study, we illustrate that single-point mutations of a highly conserved glycine residue within the linker I region of the Galpha(q) subunit confers upon the mutant Galpha(q) the ability to be activated by Galpha(i)- and Galpha(s) -coupled receptors, as evidenced by guanosine 5'-O-(3-[(35)S]thio)triphosphate binding and inositol phosphate turnover assays. The mutations did not affect expression of Galpha(q) proteins nor their ability to stimulate phospholipase Cbeta. It is noteworthy that both mutant and wild-type Galpha(q) proteins are indistinguishable in their ability to reconstitute a functional Gq-PLCbeta-calcium signaling pathway when cotransfected with the Galpha(q)-coupled neurokinin 1 or muscarinic M3 receptor into mouse embryonic fibroblasts derived from Galpha(q/11) knockout mice. On a three-dimensional model of the receptor-G protein complex, the highly conserved linker I region connecting the helical and the GTPase domain of the Galpha protein is inaccessible to the intracellular surface of the receptors. Our data indicate that receptor-G protein coupling specificity is not exclusively governed by direct receptor-G protein interaction and that it even bypasses the requirement of the extreme C terminus of Galpha, a well accepted receptor recognition domain, suggesting a novel allosteric mechanism for G protein-coupled receptor-G protein selectivity.


Effect of dichlorodifluoromethane on the appearance, viability, and integrity of Escherichia coli.
Cultures of Escherichia coli H52 were treated with liquid dichlorodifluoromethane (fluorocarbon-12 [f-12]) for 2 h at 22 C and then examined microscopically. Treated cells tended to clump, and their cytoplasms were generally less dense and less uniform in appearance than those of control cells. E. coli ML30 was exposed to f-12 at a concentration of 1.25 X saturation for times up to 1,200 min at 22 C. Cells were examined for changes in viability (plate count), permeability (as measured by exit of alpha-[14-C]methylglucoside or uptake of omicron-nitrophenyl-beta-D-galactopyranoside), release of compounds absorbing at 260 nm, and lysis (changes in absorbance at 420 nm). Large losses of alpha-methylglucoside and of percentage of viability occurred after brief exposure to f-12. Release of compounds absorbing at 260 nm occurred more slowly than the aforementioned events, possibly because these molecules are larger than alpha-methylglucoside. During 1,200-min exposure to f-12, the number of survivors decreased from 10-9 to 10-4 organisms/ml, the loss of compounds absorbing at 260 nm amounted to 50 percent, and 32 percent lysis occurred. Most of these changes occurred during the first 300 min of treatment. Loss of alpha-methylglucoside was almost complete after 1-min exposure to f-12. These results suggest that death of the cell involves several stages, with a change of permeability, occurring first, followed by leakage of compounds of increasing size and, finally, lysis.


CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of I kappa B alpha and I kappa B beta and sustained activation of nuclear factor-kappa B/c-Rel.
Unmethylated CpG dinucleotides in particular base contexts in oligonucleotides (CpG DNA) rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. Anti-IgM rapidly elevated the levels of NFkappaB p50/c-Rel heterodimers followed by a decline of p50/c-Rel heterodimers by 3 h and a concomitant increase of p50/p50 homodimers. In contrast, CpG DNA induced and maintained the levels of p50/c-Rel heterodimers in the presence or absence of anti-IgM, while control non-CpG DNA failed to induce NFkappaB activation. Anti-IgM induced IkappaB alpha degradation followed by increased IkappaB alpha protein levels. The levels of IkappaB beta were increased after anti-IgM treatment. In contrast, CpG DNA, but not non-CpG DNA, induced sustained IkappaB alpha and IkappaB beta degradation in the presence or absence of anti-IgM. Inhibition of IkappaB degradation blocked CpG DNA-induced NFkappaB activation and expression of c-myc. Prevention of NFkappaB activation by inhibiting IkappaB degradation also suppressed the ability of CpG DNA to rescue WEHI-231 cells from anti-IgM-induced apoptosis. These results indicate that CpG DNA-mediated sustained activation of NFkappaB depends on the degradation of IkappaB alpha and IkappaB beta and is required for the CpG DNA-mediated anti-apoptosis gene expression and the protection against anti-IgM-induced apoptosis of WEHI-231 cells.


The effect of adjuvant cryotherapy added to well-performed high-speed burr curettage on the long-term surgical outcomes of chondroblastoma cases.
This study aims to investigate the effect of adjuvant cryotherapy added to well-performed high-speed burr curettage on the long-term surgical outcomes of chondroblastoma cases. Between January 2004 and December 2020, a total of 30 chondroblastoma cases (19 males, 11 females; median age: 18.6 years; range, 9 to 53 years) who were surgically treated were retrospectively analyzed. The pressurized-spray technique was performed using liquid nitrogen. Data including age, sex, radiological appearance, treatment modality, duration of follow-up, skin problems, and recurrence were recorded. All patients received adjuvant liquid nitrogen cryotherapy after extended intralesional curettage with high-speed burr. The bone cavity was filled with an autologous iliac crest bone graft, allograft, or polymethylmethacrylate (PMMA). The median follow-up was 54 (range, 19 to 120) months. The lesion was located around the knee in 16 (53.3%), in the shoulder in seven (23.3%), around the hip in five (16.6%), and in the ankle in two (6.6%) cases. The defect was filled with an autologous iliac crest bone graft in 28 (93.3%), an additional allograft in eight (26.7%), and PMMA in two (6.7%) cases. Local recurrence was observed in only two (6.7%) patients during follow-up. Two (6.7%) patients developed physeal growth arrest. Osteoarthritic changes were observed in two (6.7%) patients (one knee and one hip) due to the periarticular location of the tumor. Three (10%) patients had skin complications. None of the cases had a pathological fracture. A well-performed extended intralesional curettage with high-speed burr is the first and essential step in treating chondroblastoma. Adding adjuvant liquid nitrogen cryotherapy with high-speed burr can improve treatment outcomes and significantly reduce the recurrence rate of this disease.


Influence of carbohydrates on the antigenic structure of gonadotropins: distinction of agonists and antagonists.
The biological properties of glycosylated (native) and deglycosylated gonadotropins are different. The immunological characteristics of antibodies prepared against deglycosylated lutropin and human chorionic gonadotropin were investigated. Distinct antibodies of rabbit polyclonal antisera against deglycosylated lutropin and deglycosylated chorionic gonadotropin were separated by affinity chromatography on divinylsulfonyl-Sepharose-immobilized hormone or antagonist columns, respectively, in successive runs. Antibodies that could discriminate between agonist and antagonistic forms of the hormones could thus be obtained. In radioimmunoassays using 125I-labeled antagonists and respective antagonist antibodies, only the deglycosylated hormones or their deglycosylated alpha-subunits showed preferential reaction. Based on recombinations using different deglycosylated subunits, it was concluded that the loss of antennary sugars in the alpha-subunits was mainly responsible for the changes that led to the formation of antagonist-specific antibodies. Only the agonist-specific antibody could neutralize hormone action. Thus, the type and extent of glycosylation appears to influence the antigenic structure of these secreted glycoproteins.


End-to-end Encryption for SMS Messages in the Health Care Domain.
The health care domain has a high level of expectation on security and privacy of patient information. The security, privacy, and confidentiality issues are consistent all over the domain. Technical development and increasing use of mobile phones has led us to a situation in which SMS messages are used in the electronic interactions between health care professionals and patients. We will show that it is possible to send, receive and store text messages securely with a mobile phone with no additional hardware required. More importantly we will show that it is possible to obtain a reliable user authentication in systems using text message communication. Programming language Java is used for realization of our goals. This paper describes the general application structure, while details for the technical implementation and encryption methods are described in the referenced articles. We also propose some crucial areas where the implementation of encrypted SMS can solve previous lack of security.


Covalent Capture of a Heterotrimeric Collagen Helix.
Stabilizing the three-dimensional structure of supramolecular materials can be accomplished through covalent capture of the assembled system. The lysine-aspartate charge pairs designed to direct the self-assembly of a collagen triple helix were subsequently used to covalently capture the helix through proximity-directed amide bond formation using EDC/HOBT activation. The triple helix thus stabilized maintains its folded structure and can now be used for applications previously inaccessible due to problematic folding equilibria.


Phosphorylation of Ack1 by the Receptor Tyrosine Kinase Mer.
Ack1 is a nonreceptor tyrosine kinase that is associated with cellular proliferation and survival. The receptor tyrosine kinase Mer, a member of the TAM family of receptors, has previously been reported to be an upstream activator of Ack1 kinase. The mechanism linking the two kinases, however, has not been investigated. We confirmed that Ack1 and Mer interact by co-immunoprecipitation experiments and found that Mer expression led to increased Ack1 activity. The effect on Ack1 was dependent on the kinase activity of Mer, whereas mutation of the Mer C-terminal tyrosines Y867 and Y924 did not significantly decrease the ability of Mer to activate Ack1. Ack1 possesses a Mig6 Homology Region (MHR) that contains adjacent regulatory tyrosines (Y859 and Y860). Using synthetic peptides, we showed that Mer preferentially binds and phosphorylates the MHR sequence containing phosphorylated pY860, as compared to the pY859 sequence. This suggested the possibility of sequential phosphorylation within the MHR of Ack1, as has been observed previously for other kinases. In cells co-expressing Mer and Ack1 MHR mutants, the Y859F mutant had higher activity than the Y860F mutant, consistent with this model. The interaction between Mer and Ack1 could play a role in immune cell signaling in normal physiology and could also contribute to the hyperactivation of Ack1 in prostate cancer and other tumors.


Electromyographic feedback to improve ankle dorsiflexion, wrist extension, and hand grasp.
Electromyographic feedback was used to train a patient with hemiplegia in the functional use of the muscles of his right upper and lower limbs. The patient trained with the therapist over a period of two and one-half months, engaging in exercises for ankle dorsiflexion, wrist extension, and hand grasp twice a week for one to one and one-half hours. Feedback was recorded with surface electrodes placed over the extensor surface of the forearm and the tibialis anterior; the electromyographic activity was displayed on a meter. After training, muscle control proved functional for walking, handwriting, and daily self-care activities.


Complete Resection of Pancreatoblastoma With Portal Vein Obstruction After High-dose Chemotherapy: A Case Report.
As no standard chemotherapy exists for pancreatoblastoma (PB), surgical resection is the most effective way of achieving complete remission. A 3-year-old girl with PB causing portal vein obstruction was referred to our hospital. Because of the portal vein involvement, she initially received 5 cycles of preoperative chemotherapy after biopsy, consisting of cyclophosphamide, vincristine, pirarubicin, and cisplatin. After chemotherapy, she underwent distal pancreatectomy, and the tumor was resected completely. She has been disease free for 4 years since the operation. Even in cases of advanced PB, complete surgical resection with appropriate chemotherapy can lead to complete remission.


Psychosocial management of chronic lung disorders.
Chronic lung disorders are increasingly prevalent and account for the most of the disabilities and deaths in infants and young children. The pediatrician has a unique opportunity in the early detection, counseling and referral of psychosocial problems related to chronic lung disease, as well as in assuring continuity of appropriate medical care. The present paper outlines ways the pediatrician might effectively address psychological or behavioral aspects of management of several common pediatric pulmonary disorders, namely, asthma, cystic fibrosis, bronchopulmonary dysplasia and infant tracheostomy.


COVID-19 lesion detection and segmentation-A deep learning method.
In this paper, we utilized deep learning methods to screen the positive COVID-19 cases in chest CT. Our primary goal is to supply rapid and precise assistance for disease surveillance on the medical imaging aspect. Basing on deep learning, we combined semantic segmentation and object detection methods to study the lesion performance of COVID-19. We put forward a novel end-to-end model which takes advantage of the Spatio-temporal features. Furthermore, a segmentation model attached with a fully connected CRF was designed for a more effective ROI input. Our method showed a better performance across different metrics against the comparison models. Moreover, our strategy highlighted strong robustness for the processed augmented testing samples. The comprehensive fusion of Spatio-temporal correlations can exploit more valuable features for locating target regions, and this mechanism is friendly to detect tiny lesions. Although it remains in discrete form, the feature extracting in temporal dimension improves the precision of final prediction.


Partial replacement of left hemidiaphragm in dogs by either cryopreserved or decellularized heterograft patch.
Large diaphragmatic defects are still a challenging issue for reconstruction using either synthetic prosthesis or bioprosthesis. To evaluate the possibility of using diaphragm allograft as a natural bioprosthesis in humans, we conducted a two-group study and compared cryopreserved and decellularized diaphragmatic heterograft patched in a canine model. At the end of organ harvesting from a human donor, the left hemidiaphragm was taken to the laboratory in phosphate-buffered saline solution. The next step was freezing the grafts at -80°C, and preserving them for up to 2 months in Group 1. It was subjected to a detergent-enzymatic method (containing sodium deoxycholate/DNase lavations) of decellularization for 25 cycles in Group 2. Through left thoracotomy in the eighth intercostal space, cryopreserved patches in six dogs and decellularized patches in five dogs replaced the diaphragm. During the follow-up, sonography was done in all animals, but three and two dogs in Group 1 and 2 underwent computed tomography (CT) scan, respectively. The animals were euthanized after 6 months. There was no mortality. Sonography showed only motion impairment of the patches in all cases. In Group 1, CT scan showed mild atelectasis and scattered infiltration in the left lower lobe, fibrotic bands and minimal fluid collection under the diaphragm. In Group 2, CT scan showed scattered fibrotic bands and mild to moderate elevation of the left hemidiaphragm. There was no evidence of gross disruption and complete healing of the suture line. Necropsy in both groups showed patches were completely replaced with a dense fibrous tissue. In Group 1, focal calcification was noticeable in every case and foreign body-type granulomas were clearly seen all over the grafted tissue. Histology in Group 2 animals showed less inflammatory cell infiltration and scattered foreign body granulomas in comparison with the cryopreserved patch graft. The gross healing process in the decellularized heterograft is similar to the cryopreserved diaphragm but with fewer inflammatory cells and foreign body granulomas on histology. Both of them can be used instead of bioprostheses with regard to the fact that the decellularized patch technique is more complex and expensive. It is recommended to compare them with commercial bioprostheses.


Strength of evidence of noninferiority trials with the two confidence interval method with random margin.
This article deals with the dependency(ies) of noninferiority test(s) when the two confidence interval method is employed. There are two different definitions of the two confidence interval method. One of the objectives of this article is to sort out some of the confusion in these two different definitions. In the first definition the two confidence interval method is considered as the fixed margin method that treats a noninferiority margin as a fixed constant after it is determined based on historical data. In this article the method is called the two confidence interval method with fixed margin. The issue of the dependency(ies) of noninferiority test(s) does not occur in this case. In the second definition the two confidence interval method incorporates the uncertainty associated with the estimation for the noninferiority margin. In this article the method is called the two confidence interval method with random margin. The dependency(ies) occurs, because the two confidence interval method(s) with random margin shares the same historical data. In this article we investigate how the dependency(ies) affects the unconditional and conditional across-trial type I error rates.


Priming of NK cell anti-viral effector mechanisms by direct recognition of human cytomegalovirus.
Natural killer (NK) cells play an important role in the defense against viral infections. Activation of resting NK cells is tightly controlled by the balance of surface inhibitory and activating receptors and aided by cytokines released by accessory cells along the anti-viral response. On the other hand, NK cells express functional pattern recognition receptors (PRRs) whose function has been mostly addressed by the use of synthetic agonists. The present study was undertaken to investigate whether NK cells could directly recognize a complex pathogen such as Human Cytomegalovirus (HCMV). Exposure of primary human NK cells to HCMV (TB40/E strain) induced the expression of CD69, promoted IFNγ secretion, and increased their cytotoxic activity against HCMV-infected autologous monocyte-derived dendritic cells. The divergent response induced by infective and UV-inactivated virions indicated the involvement of different NK cell sensors in the recognition of HCMV. The fact that NK cell activation could be partially prevented by blocking mAb specific for IFNAR and TLR2, together with the induction of IFNβ mRNA, supported the involvement of IFNβ and TLR2 in the response to HCMV. Thus, our data indicate that simultaneous activation of several PRRs leads to the autonomous priming of NK cell effector functions and could be a previously unappreciated mechanism presumably contributing to the control of HCMV infection.


Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.
In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.


The effect of continuous versus pericycle antiretroviral therapy on IL-2 responsiveness.
Intermittent administration of interleukin-2 (IL-2) to human immunodeficiency virus (HIV)- infected patients on antiretroviral therapy (ART) is capable of inducing significant increases in CD4 T cell counts as a result of increased T cell survival and decreased cell turnover. However, its role in the setting of ART interruptions (STI) is less well characterized. We sought to compare the effect of continuous (C) versus intermittent (P) ART on CD4 responses in patients undergoing IL-2 therapy. CD4 cell responses were compared in 25 patients who underwent IL-2 therapy during periods of continuous ART (n = 90 cycles) as well as during STI (n = 45 cycles). During STI, patients resumed ART for only 10 days surrounding each IL-2 cycle. C cycles resulted in a significantly greater CD4 gain than P cycles (Delta156 cells/microL, 95% CI = 68-243). In multivariate analyses, baseline CD4/CD25 expression and treatment arm remained strong predictors of CD4 gain while CD8/CD38+, CD8/DR+, and CD4 Ki67+ phenotype were not predictive. Continuous ART was associated with a statistically significantly greater CD4 cell response to IL-2 therapy than was intermittent ART. These observations may have important implications for the appropriate integration of IL-2 therapy into STI strategies.


[Molecular cloning of plasmid ColIb-P9 genes responsible for its mutator function].
The localization of plasmid ColIb-P9 muc genes mediating the plasmids protective and mutagenesis-increasing activity has been determined. The increase of muc genes dose by cloning them within the multicopy vector has been shown to repress the mutator function of the plasmid. No essential homology has been revealed between ColIb-P9 muc gene nucleotide sequences, pKM101 muc genes with a similar function, and umuDC chromosome genes. It has been shown that the synthesis of 38 KD protein is essential for the manifestation of the mutator function of the plasmid.


Carotid endarterectomy within 2 weeks of minor ischemic stroke: a prospective study.
Data from multicenter symptomatic trials have shown that benefit from carotid endarterectomy (CEA) was greatest in patients with carotid disease operated within 2 weeks of their last ischemic event. We prospectively analyzed the safety and benefit of CEA performed within 2 weeks of a stroke. The study involved patients with acute minor stroke admitted to two stroke units who underwent CEA within 2 weeks of their last ischemic event, once they were considered neurologically stable. Preoperative workup included scoring ischemia-related symptoms according to a modified ranking scale (mRS), carotid duplex scan, transcranial Doppler ultrasound, and head computed tomography or magnetic resonance imaging. All patients underwent neurological assessment on admission, 1 day before and 2 days after CEA, and at discharge. A complete neurological and ultrasound follow-up was performed at 1, 6, and 12 months after CEA, then yearly. All procedures were eversion CEA under deep general anesthesia, with selective shunting. Endpoints were perioperative (30-day) stroke/mortality rate or cerebral bleeding and long-term stroke recurrence or cerebral hemorrhage. Between 2000 and 2005, 102 patients with a mRS </= 2 underwent CEA within a median 8 days of acute ischemic stroke. Shunting and contralateral carotid occlusion were found significantly correlated. There were no perioperative strokes or deaths, or cerebral hemorrhage. All patients were followed up for a mean 34 months (range 1-66) with no recurrent stroke or cerebral bleeding. CEA can be performed within 2 weeks of carotid-related ischemic stroke with no perioperative stroke or cerebral bleeding, preventing the risk of stroke recurrence.


Blockade of voltage-gated calcium channel Cav1.2 and α1-adrenoceptors increases vertebral artery blood flow induced by the antivertigo agent difenidol.
Difenidol (1,1-diphenyl-4-piperidino-1-butanol hydrochloride) is an effective drug for the treatment of vertigo and dizziness. This drug is known to improve the blood flow in vertebral arteries, though the precise mechanism underlying this action remains unclear. In the present study, we investigated the effect of difenidol on voltage-gated calcium channel Ca(v)1.2 and α(1)-adrenoceptor subtypes that regulate the intracellular calcium concentration ([Ca(2+)](i)), as well as their possible involvement in the action of difenidol on vertebral artery relaxation and blood flow in dogs. In vitro binding assays demonstrated that difenidol at micromolar concentrations bound to the α(1A)-, α(1B)- and α(1D)-adrenoceptor subtypes. Difenidol inhibited the phenylephrine-induced increase in [Ca(2+)](i) in Chinese hamster ovary cells expressing human α(1A)-, α(1B)- or α(1D)-adrenoceptor subtypes with similar IC(50) values in the low micromolar range. In an electrophysiological assay, difenidol inhibited L-type calcium channel (Ca(v)1.2 subunit). In dogs, i.v. difenidol preferentially enhanced vertebral over femoral arterial blood flow. Phenylephrine and potassium induced contraction of dog vertebral arterial rings, and difenidol inhibited this action. Inhibition of phenylephrine-induced contraction by difenidol was mimicked by the α(1)-adrenoceptor antagonist phentolamine, the α(1A)-adrenoceptor antagonist RS 17,053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-α,α-dimethyl-1H-indole-3-ethanamine hydrochloride) and the α(1D)-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione dihydrochloride). In addition, the L-type calcium channel blocker nifedipine, like difenidol, attenuated the potassium-induced contraction. These findings suggest that the difenidol-induced increase in vertebral arterial blood flow may be due to vascular relaxation mediated by mixed blocking actions at α(1)-adrenoceptors and voltage-gated calcium channel Ca(v)1.2.


Three-dimensional quantitative ultrasound for detecting lymph node metastases.
Detection of metastases in lymph nodes (LNs) is critical for cancer management. Conventional histological methods may miss metastatic foci. To date, no practical means of evaluating the entire LN volume exists. The aim of this study was to develop fast, reliable, operator-independent, high-frequency, quantitative ultrasound (QUS) methods for evaluating LNs over their entire volume to effectively detect LN metastases. We scanned freshly excised LNs at 26 MHz and digitally acquired echo-signal data over the entire three-dimensional (3D) volume. A total of 146 LNs of colorectal, 26 LNs of gastric, and 118 LNs of breast cancer patients were enrolled. We step-sectioned LNs at 50-μm intervals and later compared them with 13 QUS estimates associated with tissue microstructure. Linear-discriminant analysis classified LNs as metastatic or nonmetastatic, and we computed areas (Az) under receiver-operator characteristic curves to assess classification performance. The QUS estimates and cancer probability values derived from discriminant analysis were depicted in 3D images for comparison with 3D histology. Of 146 LNs of colorectal cancer patients, 23 were metastatic; Az = 0.952 ± 0.021 (95% confidence interval [CI]: 0.911-0.993); sensitivity = 91.3% (specificity = 87.0%); and sensitivity = 100% (specificity = 67.5%). Of 26 LNs of gastric cancer patients, five were metastatic; Az = 0.962 ± 0.039 (95% CI: 0.807-1.000); sensitivity = 100% (specificity = 95.3%). A total of 17 of 118 LNs of breast cancer patients were metastatic; Az = 0.833 ± 0.047 (95% CI: 0.741-0.926); sensitivity = 88.2% (specificity = 62.5%); sensitivity = 100% (specificity = 50.5%). 3D cancer probability images showed good correlation with 3D histology. These results suggest that operator- and system-independent QUS methods allow reliable entire-volume LN evaluation for detecting metastases. 3D cancer probability images can help pathologists identify metastatic foci that could be missed using conventional methods.


Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats.
By sequestering activator calcium, the sarcoplasmic reticulum (SR) plays the central role in the excitation-contraction (E-C) cycle of cardiac muscle. Hence, functional changes in the SR in diseased myocardium might critically determine its mechanical characteristics. Previously, we demonstrated that both Ca2+ release and uptake were increased in SR isolated from hearts showing compensatory left ventricular (LV) hypertrophy taken from pressure-overloaded rats. However, it has not been elucidated whether such alterations also occur in the volume-overloaded myocardium. Rats in which volume-overloaded hypertrophy had been induced by aortocaval shunt 12 weeks prior to the investigation were compared to sham-operated controls in terms of SR Ca2+ uptake and release, and density of Ca2+ releasing channels (ryanodine receptors, RyR). Isometric tension and intracellular Ca2+ transients were also measured using the bioluminescent Ca2+ indicator, aequorin, in isolated LV papillary muscles. The extent of hypertrophy was verified by measuring the ratio of biventricular weight to body weight. In vivo, the aortocaval shunt rats showed normal LV contractility and slightly depressed LV relaxation, indicating a compensatory (adaptive) stage of LV function. In contrast, Ca2+ release, uptake, and maximal number of [3H]-ryanodine binding sites were all significantly lower in aortocaval shunt rats than in controls. Both the Ca2+ transients and isometric relaxation of the isolated myocardium were significantly prolonged in aortocaval shunt rats, though their amplitudes were similar in the two groups. Thus, the volume-overloaded cardiac hypertrophy, even at its hemodynamically compensatory (adaptive) stage, (i) was accompanied by abnormal Ca2+ handling, as indicated by prolonged intracellular Ca2+ transients and isometric tension traces, (ii) seems to involve subcellular mechanisms related to decreases in SR Ca2+ release and uptake functions, as well as to a decrease in the number of RyR. Therefore, changes in the intracellular processes underlying cardiac E-C coupling, including SR function, precede the development of this type of heart disease.


A Three-Dimensional Finite Element Analysis of the Stress Distribution Generated by Splinted and Nonsplinted Prostheses in the Rehabilitation of Various Bony Ridges with Regular or Short Morse Taper Implants.
The aim of this study was to compare the biomechanical performance of splinted or nonsplinted prostheses over short- or regular-length Morse taper implants (5 mm and 11 mm, respectively) in the posterior area of the mandible using finite element analysis. Three-dimensional geometric models of regular implants (Ø 4 × 11 mm) and short implants (Ø 4 × 5 mm) were placed into a simulated model of the left posterior mandible that included the first premolar tooth; all teeth posterior to this tooth had been removed. The four experimental groups were as follows: regular group SP (three regular implants were rehabilitated with splinted prostheses), regular group NSP (three regular implants were rehabilitated with nonsplinted prostheses), short group SP (three short implants were rehabilitated with splinted prostheses), and short group NSP (three short implants were rehabilitated with nonsplinted prostheses). Oblique forces were simulated in molars (365 N) and premolars (200 N). Qualitative and quantitative analyses of the minimum principal stress in bone were performed using ANSYS Workbench software, version 10.0. The use of splinting in the short group reduced the stress to the bone surrounding the implants and tooth. The use of NSP or SP in the regular group resulted in similar stresses. The best indication when there are short implants is to use SP. Use of NSP is feasible only when regular implants are present.


Zinc Hyperaccumulation in Plants: A Review.
Zinc is an essential microelement involved in many aspects of plant growth and development. Abnormal zinc amounts, mostly due to human activities, can be toxic to flora, fauna, and humans. In plants, excess zinc causes morphological, biochemical, and physiological disorders. Some plants have the ability to resist and even accumulate zinc in their tissues. To date, 28 plant species have been described as zinc hyperaccumulators. These plants display several morphological, physiological, and biochemical adaptations resulting from the activation of molecular Zn hyperaccumulation mechanisms. These adaptations can be varied between species and within populations. In this review, we describe the physiological and biochemical as well as molecular mechanisms involved in zinc hyperaccumulation in plants.


[Effects of probiotics on intestinal bacterial colonization in premature infants].
To study the possible roles of probiotics in decreasing intestinal bacterial colonization rate and the incidence of enterogenic infections in premature infants. Seventy premature infants were randomly assigned to two groups: probiotics and conventional treatment groups (control) (n=35 each). The probiotics treatment group was administered with oral Clostridium butyricum powder (250 mg, twice daily up to discharge) 24 hrs after birth except conventional treatment. Rectal swab cultures were done at admission, 5 and 12 days after admission, and before discharge. Clinical and laboratory findings were compared between the two groups. The intestinal bacterial colonization rate in the probiotics treatment group was lower than that in the control group 12 days after admission (60% vs 83%; p<0.05) and before discharge (51% vs 80%; p<0.05). Klebsiella pneumoniae, Escherichia coli and Enterococcus faecium were common colonization bacteria in the two groups. Diarrhea occurred in 7 cases (20%) in the probiotics treatment group compared with 16 cases (46%) in the control group (p<0.05). Two infants (6%) developed sepsis in the probiotics treatment group compared with 9 cases (26%) in the control group (p<0.05). Probiotics can decrease intestinal bacterial colonization rate and the incidence of diarrhea and sepsis in premature infants.


Nonadiabatic alignment of asymmetric top molecules: rotational revivals.
The rotational revival structure of asymmetric top molecules, following irradiation by an intense picosecond laser pulse, is explored theoretically and experimentally. Numerically we solve nonperturbatively for the rotational dynamics of a general asymmetric top subject to a linearly polarized intense pulse, and analyze the dependence of the dynamical alignment on the field and system parameters. Experimentally we use time-resolved photofragment imaging to measure the alignment of two molecules with different asymmetry, iodobenzene, and iodopentafluorobenzene. Our numerical results explain the experimental observations and generalize them to other molecules. The rotational revival structure of asymmetric tops differs qualitatively from the intensively studied linear top case. Potentially it provides valuable structural information about molecules.


HIV-associated nephropathy. A unique combined glomerular, tubular, and interstitial lesion.
Although a variety of renal lesions may occur in acquired immune deficiency syndrome (AIDS), a rare but aggressive form of focal and segmental glomerulosclerosis with capillary collapse has been considered a possible component of this disorder. It is manifested by heavy proteinuria and progression to renal failure in a short time. We studied renal biopsies from nine patients with HIV infection and the above clinical features and compared the renal tissues to biopsies from HIV-positive individuals with immune complex glomerulonephritis and to biopsies from patients with heroin abuse nephropathy. The HIV-associated nephropathy was characterized by a combination of lesions: focal and segmental glomerulosclerosis, often in an early stage of evolution and with prominent degenerative changes of visceral epithelium; tubular necrosis without identifiable nephrotoxic or hemodynamic etiology; interstitial edema; large plasma protein-containing tubular casts in all segments of the nephron associated with marked tubular dilatation; and widespread tubuloreticular structures in vascular endothelium. In contrast, neither the sclerosing glomerular changes nor the tubulointerstitial abnormalities were present in HIV-infected patients with immune complex glomerulonephritis. Similarly, the tubular and interstitial changes and widespread tubuloreticular structures were absent in heroin-abuse nephropathy. The lesions of HIV-associated nephropathy occurred in patients with AIDS, AIDS-related complex, and in individuals clinically asymptomatic for HIV infection. Their morphological features in asymptomatic patients are sufficiently specific to allow for accurate diagnosis of HIV infection.


Classification and quantification analysis of peach kernel from different origins with near-infrared diffuse reflection spectroscopy.
Peach kernels which contain kinds of fatty acids play an important role in the regulation of a variety of physiological and biological functions. To establish an innovative and rapid diffuse reflectance near-infrared spectroscopy (DR-NIR) analysis method along with chemometric techniques for the qualitative and quantitative determination of a peach kernel. Peach kernel samples from nine different origins were analyzed with high-performance liquid chromatography (HPLC) as a reference method. DR-NIR is in the spectral range 1100-2300 nm. Principal component analysis (PCA) and partial least squares regression (PLSR) algorithm were applied to obtain prediction models, The Savitzky-Golay derivative and first derivative were adopted for the spectral pre-processing, PCA was applied to classify the varieties of those samples. For the quantitative calibration, the models of linoleic and oleinic acids were established with the PLSR algorithm and the optimal principal component (PC) numbers were selected with leave-one-out (LOO) cross-validation. The established models were evaluated with the root mean square error of deviation (RMSED) and corresponding correlation coefficients (R (2)). The PCA results of DR-NIR spectra yield clear classification of the two varieties of peach kernel. PLSR had a better predictive ability. The correlation coefficients of the two calibration models were above 0.99, and the RMSED of linoleic and oleinic acids were 1.266% and 1.412%, respectively. The DR-NIR combined with PCA and PLSR algorithm could be used efficiently to identify and quantify peach kernels and also help to solve variety problem.


An approach to studying scale for students in higher education: a Rasch measurement model analysis.
A questionnaire comprising 80 self-report items was designed to measure student Approaches to Studying in a higher education context. The items were conceptualized and designed from five learning orientations: a Deep Approach, a Surface Approach, a Strategic Approach, Clarity of Direction and Academic Self-Confidence, to include 40 attitude items and 40 corresponding behavior items. The study aimed to create a scale and investigate its psychometric properties using a Rasch measurement model. The convenience sample consisted of 350 students at an Australian university in 1998. The analysis supported the conceptual structure of the Scale as involving studying attitudes and behaviors towards five orientations to learning. Attitudes are mostly easier than behaviors, in line with the theory. Sixty-eight items fit the model and have good psychometric properties. The proportion of observed variance considered true is 92% and the Scale is well-targeted against the students. Some harder items are needed to improve the targeting and some further testing work needs to be done on the Surface Approach. In the Surface Approach and Clarity of Direction in Studying, attitudes make a lesser contribution than behaviors to the variable, Approaches to Studying.


Spontaneous bilateral rod fracture of malleable penile prosthesis.
Mechanical failure with a malleable penile prosthesis is very rare. To the best of our knowledge, this is the first case reporting on a bilateral AMS 650 rod mechanical failure. We present a 50-year-old man with organic erectile dysfunction who experienced bilateral AMS 650 rod fracture after 14 years. The rod fracture of the left side was confirmed via X-ray preoperatively. The surgical exploration revealed a fracture of both rods. After the removal of both rods, we implanted a new malleable device during the same session. At the 6-month follow-up, the patient was satisfied with his prosthesis.


Recent progress in GM-CSF-based cancer immunotherapy.
Cancer immunotherapy is a growing field. GM-CSF, a potent cytokine promoting the differentiation of myeloid cells, can also be used as an immunostimulatory adjuvant to elicit antitumor immunity. Additionally, GM-CSF is essential for the differentiation of dendritic cells, which are responsible for processing and presenting tumor antigens for the priming of antitumor cytotoxic T lymphocytes. Some strategies have been developed for GM-CSF-based cancer immunotherapy in clinical practice: GM-CSF monotherapy, GM-CSF-secreting cancer cell vaccines, GM-CSF-fused tumor-associated antigen protein-based vaccines, GM-CSF-based DNA vaccines and GM-CSF combination therapy. GM-CSF also contributes to the regulation of immunosuppression in the tumor microenvironment. This review provides recommendations regarding GM-CSF-based cancer immunotherapy.


Campylobacteriosis in urban versus rural areas: a case-case study integrated with molecular typing to validate risk factors and to attribute sources of infection.
Campylobacter infection is a leading cause of bacterial gastroenteritis worldwide, and most clinical cases appear as isolated, sporadic infections for which the source is rarely apparent. From July 2005 to December 2007 we conducted a prospective case-case study of sporadic, domestically-acquired Campylobacter enteritis in rural versus urban areas and a prevalence study of Campylobacter in animal and environmental sources in the Eastern Townships, Quebec. Isolates were typed using Multilocus Sequence Typing (MLST) to reinforce the case-case findings and to assign a source probability estimate for each human isolate. The risk of human campylobacteriosis was 1.89-fold higher in rural than urban areas. Unconditional multivariate logistic regression analysis identified two independent risk factors associated with human Campylobacter infections acquired in rural area: occupational exposure to animals (OR = 10.6, 95% CI: 1.2-91, p = 0.032), and household water coming from a private well (OR = 8.3, 95% CI: 3.4-20.4, p<0.0001). A total of 851 C. jejuni isolates (178 human, 257 chicken, 87 bovine, 266 water, 63 wild bird) were typed using MLST. Among human isolates, the incidence rates of clonal complexes (CC) CC-21, CC-45, and CC-61 were higher in rural than urban areas. MLST-based source attribution analysis indicated that 64.5% of human C. jejuni isolates were attributable to chicken, followed by cattle (25.8%), water (7.4%), and wild birds (2.3%). Chicken was the attributable source for the majority of cases, independent of residential area, sex and age. The increased incidence in rural compared to urban areas was associated with occupational exposure to animals, particularly cattle among those aged 15-34 years, and with consumption of private well water. Both bovine and water exposure appeared to contribute to the seasonal variation in campylobacteriosis. These results provide a basis for developing public education and preventive programs targeting the risk factors identified.


Dialysis as a Treatment Option for a Patient With Normal Kidney Function and Familial Tumoral Calcinosis Due to a Compound Heterozygous FGF23 Mutation.
Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%. Parathyroid hormone was suppressed (15 pg/mL), associated with a low-normal 25-hydroxyvitamin D (26 ng/mL) concentration but high 1,25-dihydroxyvitamin D concentration (92 pg/mL). Serum intact FGF-23 (fibroblast growth factor 23) was undetectable. Genetic analysis revealed tumoral calcinosis due to a compound heterozygous mutation in FGF23, c.201G>C (p.Gln67His) and c.466C>T (p.Gln156*). Due to lack of other treatment options and because the patient was facing severe vascular complications, we initiated a daily hemodialysis program even in the setting of normal kidney function. This unusual therapeutic option successful controlled hyperphosphatemia and reduced metastatic tumoral lesions. This is a report of a new mutation in FGF23 in which dialysis was an effective treatment option for tumoral calcinosis with normal kidney function.


A feasibility study on the adoption of e-learning for public health nurse continuing education in Taiwan.
The purpose of this study is to investigate the feasibility of developing e-learning and to examine reasons for adopting or rejecting e-learning as an alternative way to conduct continuing education (CE) for public health nurses (PHNs). A nationwide-based cross-sectional study was conducted with a randomly selected sample of 233 PHNs in Taiwan. A structured questionnaire was used to collect data by mailing methods. The majority of PHNs (88.84%, n=207) showed an affirmative intention towards adopting e-learning as their one way of CE. Reasons for adopting e-learning included achieving life learning, fulfilling personal interests, time-saving, based on job needs, information diversity, flexible in time and space, self-regulatory learning, cost-effectiveness, less impact on family duties and life. Twenty-six PHNs (11.16%) who rejected e-learning as their way of CE indicated main reasons including poor computer competence, lack of personal computer and without internet access, heavy work load, heavy family duties, conflict with personal preference, heavy economic burden, lack of motivation, and low self-control. This study reveals a high feasibility of developing e-learning that coexists with other CE models (e.g. traditional instruction). Reasons analyses provide directions for decreasing barriers for developing a learning model of this new medium for nurses' CE.


The "Knapp-Ronne" type of malignant melanoma of the choroid. A haemangioma-like melanoma with a typical clinical picture. So-called "preretinal malignant choroidal melanoma".
Five cases of a rare type of malignant melanoma of the choroid with a typical clinical and histopathological picture are reported. This tumour is characterized by it location near the optic disk,its early growth through the retina, its structure with bloodless and blood-filled cavernous spaces, and its manifestation by a massive haemorrhage into the vitreous. "Historical" cases are mentioned, showing that this rare tumour, occurring in about 1:250 of malignant melanomas of the choroid, has a Scandinavian tradition. The clinical and histopathological details are discussed.


PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing.
Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg(2+) and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles.


Mitochondrial genome sequence comparisons indicate that the elephant louse Haematomyzus elephantis (Piaget, 1869) contains cryptic species.
The parvorder Rhynchopthirina contains three currently recognised species of lice that parasitize elephants (both African savanna elephant Loxodonta africana and Asian elephant Elephas maximus), desert warthogs (Phacochoerus aethiopicus) and Red River hogs (Potamochoerus porcus), respectively. The Asian elephant lice and the African savanna elephant lice are currently treated as the same species, Haematomyzus elephantis (Piaget, 1869), based on morphology despite the fact that their hosts diverged 8.4 million years ago. In the current study, we sequenced 23 mitochondrial (mt) genes of African savanna elephant lice collected in South Africa and analysed the sequence divergence between African savanna elephant lice and previously sequenced Asian elephant lice. Sequence comparisons revealed >23% divergence for the 23 mt genes as a whole and ~17% divergence for cox1 gene between African savanna and Asian elephant lice, which were far higher than the divergence expected within a species. Furthermore, the mt gene sequence divergences between these lice are 3.76-4.6 times higher than that between their hosts, the African savanna and Asian elephants, which are expected for the co-divergence and co-evolution between lice and their elephant hosts. We conclude that (1) H. elephantis (Piaget, 1869) contains cryptic species and (2) African savanna and Asian elephant lice are different species genetically that may have co-diverged and co-evolved with their hosts.


Prevalence of blindness and its determinants in Bangladeshi adult population: results from a national cross-sectional survey.
The objective of this study was to determine the prevalence of blindness and its determinants in Bangladeshi adult population. A cross-sectional population-based survey conducted at household level with national representation. Samples were drawn from the 2011 national census frame using a multistage stratified cluster sampling method. The survey was done in urban and rural areas in 2013 using a probability proportionate to size sampling approach to locate participants from 72 primary sampling units. One man or one woman aged ≥40 years was randomly selected from their households to recruit 7200. In addition to sociodemographic data, information on medication for hypertension and diabetes was obtained. Blood pressure and capillary blood glucose were measured. Eyelids, cornea, lens, and retina were examined in addition to visual acuity and refraction testing. The following definition was used to categorise subjects having (1) blindness: visual acuity <3/60, (2) low vision: ≥3/60 to <6/60 and (3) normal vision: ≥6/12 after best correction. We could recruit 6391 (88.8%) people among whom 2955 (46.2%) were men. Among them, 1922 (30.1%) were from urban and 4469 (69.9%) were from rural areas. The mean age was 54.3 (SD 11.2) years. The age-standardised prevalence, after best correction, of blindness and low vision was 1.0% (95% CI 0.5% to 1.4%) and 12.1% (95% CI 10.5% to 13.8%), respectively. Multivariable logistic regression indicated that cataract, age-related macular degeneration and diabetic retinopathy were significantly associated with low vision and blindness after adjustment for age and sex. Population attributable risk of cataract for low vision and blindness was 79.6%. Low vision and blindness are common problems in those aged 40 years or older. Extensive screening and eye care services are necessary for wider coverage engaging all tiers of the healthcare system especially focusing on cataract.


Brain-gut communication via vagus nerve modulates conditioned flavor preference.
It is well known that the postingestive effect modulates subsequent food preference. We previously showed that monosodium L-glutamate (MSG) can increase flavor preference by its postingestive effect. The neural pathway involved in mediating this effect, however, remains unknown. We show here the role of the vagus nerve in acquiring this learned flavor preference and in the brain's response to intragastric glutamate infusion. Adult rats with an intragastric cannula underwent total abdominal branch vagotomies (TVX), common hepatic branch vagotomies (HVX), total abdominal branch vagotomies with the common hepatic branch intact (TVXh), or sham operations (Sham). Following recovery, rats were subjected to a conditioned flavor preference paradigm, in which they drank a flavored solution (CS+) paired with intragastric MSG or another flavored solution (CS-) paired with intragastric distilled water. After conditioning, the Sham and HVX groups demonstrated significantly higher intake of CS+ than CS-, whereas the TVXh and TVX groups showed no significant differences. We then conducted an fMRI study to identify the brain areas that responded to the intragastric glutamate in each group. In the Sham, HVX and TVXh groups, intragastric MSG significantly increased the BOLD intensity in the nucleus of the solitary tract. The amygdala, hippocampus and lateral hypothalamus were also activated in the Sham and HVX groups but not in the TVXh and TVX groups. These results indicate that the abdominal vagus nerve is necessary for acquiring preference and that the lateral hypothalamus and limbic system could be key areas for integrating the information on gut glutamate and oronasal stimuli.


Benzo[a]pyrene aggravates atopic dermatitis-like skin lesions in mice.
Background: Benzo[a]pyrene (BaP) affects the immune system and causes mutagenic and carcinogenic effects. Purpose: We aimed to evaluate the effects of systemic exposure to BaP on mite allergen-induced atopic dermatitis (AD)-like skin lesions in mice. Methods: Mite allergen (Dermatophagoides pteronyssinus; Dp) was injected intradermally into the right ears of NC/Nga male mice on eight occasions every 2-3 days. Benzo[a]pyrene was administered intraperitoneally in the equivalent doses of 0, 2, 20, 200, or 2000 μg/kg/day, once a week on four occasions. Results: AD-like skin inflammation related to mite allergen worsened by BaP exposure at 2, 20 µg/kg/day doses; this was in parallel with eosinophil and mast cell infiltration and mast cell degranulation. A trend was also observed toward increased proinflammatory molecule expression, including macrophage inflammatory protein-1 alpha, interleukin (IL)-4, IL-13, and IL-18, in the ear tissue. However, 200 or 2000 µg/kg/day BaP attenuated the enhancing effects. In the regional lymph nodes, 2 µg/kg/day BaP with Dp enhanced antigen-presenting cell and T cell activation compared with Dp alone. Conclusions: This suggests that BaP exposure can aggravate Dp-induced AD-like skin lesions through TH2-biased responses in the inflamed sites and the activation of regional lymph nodes. Therefore, BaP may be responsible for the recent increase in AD incidence.


Prevalence and predictors of squamous intraepithelial lesions in human immunodeficiency virus positive women in Sagamu, southwest Nigeria.
Cervical cancer is still a public health problem in many developing countries, like Nigeria. HIV infection makes HPV infections last longer, progress to squamous intraepithelial lesion of the cervix, and eventually lead to invasive cervical cancer. Find out how often squamous intraepithelial lesions (SIL) happen and what causes them in HIV-positive women in Sagamu, southwest Nigeria. A cross-sectional study was done with 165 women with HIV and 165 women without HIV. Pap smears were done on all of the people in the study. The data was looked at with IBM-SPSS Windows v. 23. Both groups were about the same age and had the same number of children (P=0.194 and P=0.388, respectively). The participants' average age (SD) was 36.8 (5.6), and the median number of children they had was 3. HIV-positive women were much more likely to have an abnormal cytology smear (24.8%) than HIV-negative women (7.3%) (2 = 18.904, P 0.001). There wasn't a link between having HIV and the severity of cervical lesions (2 = 3.66, P = 0.162). A CD4 cell count of less than 350 cells/mm3was found to be a strong predictor of an abnormal cervical cytological smear in HIV-positive women (AOR: 25.5; CI: 8.8-73.5; P 0.001). In Sagamu, Nigeria, the number of HIV-positive women with SIL of the cervix was much higher than the number of HIVnegative women with SIL of the cervix. HIV-positive women, especially those with a low number of CD4 cells, need cervical smear tests more often. This will make sure that pre-invasive lesions are found and treated as soon as possible.


Pulmonary capillary permeability - a transfusion lesion.
Massive transfusion of bank blood has been implicated as a major etiologic factor in the evolution of pulmonary insufficiency after injury. In spite of the demonstration of significant debris, including aggregates, in stored blood, a precise and reproducible pulmonary effect of transfusion has not previously been demonstrated. Since clinical pulmonary insufficiency is frequently accompanied by increased lung water, these experiments were designed to measure pulmonary capillary permeability and its response to transfusion of blood and blood components in rats. These experiments demonstrate that: 1) the rat lung is a target organ with regard to blood transfusion; 2) the lung lesion with transfusion is attributable, at least in part, to a selective and acute increase in pulmonary capillary permeability; 3) pulmonary capillary permeability is highly responsive to viable platelets; 4) prolonged storage of blood in polyvinyl chloride containers may enhance its ability to induce pulmonary capillary permeability; 5) increased capillary permeability with transfusion is largely eliminated when platelets and buffy coat are eliminated.


Two cases of amiodarone-induced thyrotoxicosis successfully treated with a short course of antithyroid drugs while amiodarone was continued.
Two patients with amiodarone-induced thyrotoxicosis were treated successfully with potassium perchlorate and carbimazole while treatment with amiodarone was continued. These antithyroid drugs were stopped after the patients had became clinically and biochemically euthyroid. During follow up, when treatment with amiodarone continued, thyrotoxicosis did not recur. Amiodarone-induced thyrotoxicosis seems to be a transient condition that can be treated successfully with a short course of antithyroid drugs without stopping amiodarone treatment.


Role of epithelial mesenchymal transition in prostate tumorigenesis.
Globally, the cancer associated deaths are generally attributed to the spread of cancerous cells or their features to the nearby or distant secondary organs by a process known as metastasis. Among other factors, the metastatic dissemination of cancer cells is attributed to the reactivation of an evolutionary conserved developmental program known as epithelial to mesenchymal transition (EMT). During EMT, fully differentiated epithelial cells undergo a series of dramatic changes in their morphology, along with loss of cell to cell contact and matrix remodeling into less differentiated and invasive mesenchymal cells. Many studies provide evidence for the existence of EMT like states in prostate cancer (PCa) and suggest its possible involvement in PCa progression and metastasis. At the same time, the lack of conclusive evidence regarding the presence of full EMT in human PCa samples has somewhat dampened the interest in the field. However, ongoing EMT research provides new perspectives and unveils the enormous potential of this field in tailoring new therapeutic regimens for PCa management. This review summarizes the role of many transcription factors and other molecules that drive EMT during prostate tumorigenesis.


Costs of hospitalization with respiratory syncytial virus illness among children aged <5 years and the financial impact on households in Bangladesh, 2010.
Respiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children <5 years and associated financial impact on households in Bangladesh. Data of this study could be useful for RSV vaccine development and also the value of various preventive strategies, including use of an RSV vaccine in children if one becomes available. From May through October 2010, children aged <5 years with laboratory-confirmed RSV were identified from a sentinel influenza program database at four tertiary hospitals. Research assistants visited case-patients' homes after hospital discharge and administered a structured questionnaire to record direct medical costs (physician consultation fee, costs for hospital bed, medicines and diagnostic tests); non-medical costs (costs for food, lodging and transportation); indirect costs (caregivers' productivity loss), and coping strategies used by families to pay for treatment. We used WHO-Choice estimates for routine health care service costs. We added direct, indirect and health care service costs to calculate cost-per-episode of severe RSV illness. We used Monte Carlo simulation to estimate annual economic burden for severe RSV illness. We interviewed caregivers of 39 persons hospitalized for RSV illness. The median direct cost for hospitalization was US$ 62 (interquartile range [IQR] = 43-101), indirect cost was US$ 19 (IQR = 11-29) and total cost was US$ 94 (IQR = 67-127). The median out-of-pocket cost was 24% of monthly household income of affected families (US$ 143), and >50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV-associated hospitalization in children aged <5 years in Bangladesh was US$ 10 million (IQR: US$ 7-16 million), the median indirect cost was US$ 3.0 million (IQR: 2-5 million) in 2010. RSV-associated hospitalization among children aged <5 years represents a substantial economic burden in Bangladesh. Affected families frequently incurred considerable out of pocket and indirect costs for treatment that resulted in financial hardship.


A Case of Hemophagocytic Syndrome due to Tuberculosis: Uncommon Manifestation of a Common Disease.
Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is the manifestation of immune dysregulation. It is associated with ineffective but exaggerated immune response and infiltration of active lymphocytes and histiocytes in various organs. This devastating clinical condition has myriad of clinical and biochemical manifestations such as fever, splenomegaly, pancytopenia, hypertrygliceridemia, and hyperferritinemia. It can be either primary or secondary. Primary HLH usually presents in childhood. Secondary HLH occurs due to infection mostly viruses but other aetiologies are also important as early detection and treatment may improve survival. Hemophagocytosis due to tuberculosis is uncommon. Only handful of cases have been reported mostly in immunocompromised patients. We report a case of hemophagocytic syndrome associated with disseminated tuberculosis in an immunocompetent women highlighting early diagnosis and treatment is a demanding need in this devastating disease.


Molecular Design, Synthesis, and Asymmetric Catalysis of a Hexacoordinated Chiral Phosphate Ion.
We describe the design, synthesis, and characterization of a chiral hexacoordinated phosphate ion that features an octahedral P(V) core consisting of two N,N,O-tridentate backbones. We further demonstrate that the corresponding hydrogen phosphate acts as an effective catalyst for a highly enantioselective Pictet-Spengler-type reaction, wherein the relationship between the structure of the chiral phosphate ion and its ability to dictate the absolute stereochemistry is revealed in conjunction with precise structural elucidation of the phosphate ion.


Medical perspective in testicular ischemia-reperfusion injury.
Testicular torsion or torsion of the spermatic cord is one of the most serious urological conditions. It causes testicular injury, which potentially leads to male subfertility. The turning of the spermatic cord and spermatic structures around themselves results in biochemical and histological changes; however, following testicular detorsion, tissues undergo reperfusion that causes more severe damage than that induced by ischemia. Since the primary causes of testicular damage are reactive oxygen species production, an increase in intra-mitochondrial calcium concentration and an increased rate of cellular apoptosis, different medications may potentially be effective. It seems that several medications, experimentally and sometimes clinically, serve an adjuvant role in the cellular damage that occurs following ischemia-reperfusion. Antioxidants, calcium channel blockers, phytotherapeutical medicinals, anaesthetics, hormones and platelet inhibitors may potentially create a solid basis for an adjuvant restoring therapy and ameliorate testicular function following torsion. The current study aimed to review the relevant literature and discuss the actions of a number of molecules that may protect the testes during ischemia/reperfusion injury.


Influence of droplet deformability on the coalescence rate of emulsions.
In this article the influence of deformation on the coalescence rates of oil-in-water (O/W) emulsions is analyzed. Calculations for doublets and many-particles systems were performed based on a Brownian dynamics algorithm. Extensional and bending energies were included in order to quantify the effect of the changes in the surface geometry on the coalescence rates. Also, the hydrodynamic resistance due to the flat film was included through a correction to the diffusion coefficient in the lubrication limit. Results of two particles calculations were compared with previous analytical evaluations of the coalescence time in absence of highly repulsive barriers [Danov, Langmuir 9, 1731 (1993)]. Lifetime of doublets was calculated as a function of the particle radius from 100 nm to 100 microm. It was found that the doublets lifetime strongly depends on the interplay between the potential of interaction between the droplets and the hydrodynamic resistance. Depending on the repulsive barrier either a monotonous increase of the lifetime with the droplet size or a maximum value is observed. Finally, the evolution of O/W emulsions with a volume fraction of phi=0.10 was studied. For these many-particle systems, the results show a sensitive dependence of the aggregation behavior on the interfacial tension. The procedure reported here allows us to include Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO forces and the film drainage velocity of many different systems.


Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke.
Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke obtained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/m3 air). The efficacy of exposure was assessed by measuring urine nicotine and cotinine levels. Cigarette smoke did not change total cytochrome P450 and b5 protein levels in any of the organs studied, and most of these organs did not show any changes in the activity of reductases associated with these cytochromes. Following exposure to tobacco smoke, fetal rat liver expressed CYP2B1/2 protein; in newborns (day 1) both liver and lung showed CYP2B1/2 protein expression and very low pentoxyresorufin O-dealkylase activity. Western blot analysis of adult liver, lung, heart, but not of brain microsomes, showed that tobacco smoke induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was lower in the livers and hearts of pregnant females. In the rat and human placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke-induced expression at the protein level. This study shows clearly that the expression of CYP2B1/2, which metabolizes nicotine and some drugs and activates carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific regulatory mechanisms.


Critical slowing down as a biomarker for seizure susceptibility.
The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.


Genetic diversity of Glossina fuscipes fuscipes along the shores of Lake Victoria in Tanzania and Kenya: implications for management.
Tsetse flies (Diptera: Glossinidae) are sole vectors for trypanosomiasis, which affect human health and livestock productivity in Africa. Little is known about the genetic diversity of Glossina fuscipes fuscipes, which is an important species in Tanzania and Kenya. The main objective of the study was to provide baseline data to determine the genetic variability and divergence of G. f. fuscipes in the Lake Victoria basin of Tanzania and Kenya in order to guide future vector control efforts in the region. Two hundred and seventy five G. f. fuscipes from 8 sites along the shores of Lake Victoria were screened for genetic polymorphisms at 19 microsatellite loci. Samples were collected from two sites in Kenya and six sites in Tanzania. Four of the Tanzanian sites were located in the Rorya district, on the eastern shores of Lake Victoria, while the other two sites were from Ukerewe and Bukoba districts from the southern and western Lake Victoria shores, respectively. Four genetically distinct allopatric clusters were revealed by microsatellite analysis, which sorted the sampling sites according to geography, with sites separated by as little as ~65 km belonging to distinct genetic clusters, while samples located within ~35 km from each other group in the same cluster. Our results suggest that there is ongoing genetic admixture within sampling sites located ~35 km from each other, while sites located ~65 km apart are genetically isolated from each other. Similar patterns emerged from a parallel study on G. f. fuscipes analyzed from the Lake Victoria Uganda shores. From a control perspective these results suggest that for sites within the same genetic cluster, control efforts should be carried out in a coordinated fashion in order to avoid re-invasions. Future work should focus on better quantifying the extent and spatial patterns of the observed genetic discontinuities of the G. f. fuscipes populations along the Tanzanian shores. This will aid in their control by providing guidelines on the geographical extent of the area to be treated at the same time.


Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trial.
The impact of virologic response on hepatic function has not been previously defined. To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) +/- ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR). Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24-(13)C]cholate, galactose and (99m)Tc-sulfur colloid were administered intravenously; [2,2,4,2-(2)H]cholate, [1-(13)C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath (13)CO(2), monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. Rates of SVR were 18-26% in patients with good function by QLFTs, but < or =6% in patients with poor function. Hepatic metabolism, measured by caffeine k(elim) (P = 0.02), antipyrine k(elim) (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cl(oral) (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM.


Efficacy of Atorvastatin in Prevention of Contrast-induced Nephropathy in High-risk Patients Undergoing Angiography: A Double-blind Randomized Controlled Trial.
To evaluate the efficacy and safety of atorvastatin (ATN) 80 mg in the prevention of contrast medium- induced nephropathy (CIN) in high risk patients undergoing angiograph. This was a prospective, double-blind, two-arm, parallel group RCT. A total of 216 patients undergoing coronary angiography were screened, and 188 eligible patients were randomized to two treatment arms. Patients in Group A received tablet N-acetylcysteine (NAC) 1200 mg once daily, and patients in Group B received tablet atorvastatin 80 mg + NAC 1200 mg once daily, for 3 days before, and 2 days after angiography. A total of 160 patients completed the trial. Postprocedure, nine and two CIN cases were found in Group A and B, respectively. The mean change in serum creatinine was 0.086 ± 0.168 in Group A and 0.021 ± 0.083 in Group B, which was statistically significant (P = 0.0289). Postprocedure, the estimated glomerular filteration rate was reduced by 19.52 in Group A and 13.55 in Group B (P = 0.003). This trial indicates the positive role of statins in preventive strategy against CIN along with NAC.


Management and outcome of early glottic carcinoma.
We designed a retrospective study to analyze treatment methods and outcomes for patients with lesions ranging from carcinoma in situ to invasive T1 glottic squamous cell carcinoma. Patients with nonsquamous cell carcinoma, verrucous variant of squamous cell carcinoma, anterior commissure involvement, and T2 lesions were excluded. University of Pittsburgh School of Medicine, a tertiary referral center. Fifty-four patients met the inclusion criteria. Mean follow-up was 49 months (range 24 to 96 months). Forty-eight of 54 (89%) were treated with endoscopic excision. Forty of these 48 patients (83%) were successfully treated with endoscopic excision(s) as the only treatment modality. Four patients had persistence of disease despite multiple endoscopic excisions. Two of these patients underwent hemilaryngectomy, 1 received radiation treatment, and 1 received radiation therapy followed by a hemilaryngectomy. Four patients had recurrence of disease. Two patients with recurrence required radiation therapy and 2 patients required a total laryngectomy. With the selective application of multiple endoscopic excisions, radiation therapy, and more invasive operation, 100% of patients are without evidence of disease with a laryngeal preservation rate of 96%. This study supports the use of endoscopic excisional biopsy as the primary treatment modality for lesions ranging from carcinoma in situ to invasive T1 glottic carcinoma. This study also highlights the importance of close clinical follow-up and the potential need for further treatment. By reserving open operation and radiation therapy to selective cases, we successfully treated all patients while limiting the disadvantages of radiation therapy and more invasive operation to the minority of patients.


New antigenic targets in type 1 diabetes.
The beta-cell-specific zinc transporter isoform 8 (SLC30A8) has recently emerged both as a major autoantigenic target of type 1 diabetes and also as a genetic marker for type 2 diabetes. We examine the hypothesis that the cell specificity and cellular localization of this granule membrane protein are significant factors in its contribution to the pathogenesis of these diseases. Both type 1 diabetes and type 2 diabetes are associated with islet functional failure and both diseases may be linked to stress responses and changes in the secretory pathway, which lead to cell apoptosis and thus directly to reduction of beta-cell mass or activation of underlying autoimmunity. In both cases, the common polymorphism at aa 325 has been implicated in disease, in type 1 diabetes by determining the autoantibody epitope specificity and in type 2 diabetes through association with altered beta-cell mass and impaired secretion. Functional studies of the transporter will be key to understanding the role of ZnT8 in type 2 diabetes. Investigation of the cellular immune response to ZnT8 will be essential in evaluating its contribution to type 1 diabetes. Measurement of autoantibodies to ZnT8 takes us a step closer to detection of prediabetes in the general population.