Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen.
Passive Heymann nephritis (PHN) is a model of human membranous nephropathy that is characterized by formation of granular subepithelial immune deposits in the glomerular capillary wall which results in complement activation. This is causally related to damage of the filtration barrier and subsequent proteinuria. The local accumulation of injurious reactive oxygen species (ROS) is a major effector mechanism in PHN. ROS may induce tissue damage by initiating lipid peroxidation (LPO). In turn, this leads to adduct formation between breakdown products of LPO with structural proteins, such as formation of malondialdehyde (MDA) or 4-hydroxynonenal-lysine adducts. To examine the role of LPO in the development of proteinuria we have localized MDA and 4-hydroxynonenal-lysine adducts in glomeruli of PHN rats by immunofluorescence microscopy, using specific monoclonal antibodies. By immunogold electron microscopy, MDA adducts were localized to cytoplasmic vesicles and cell membranes of glomerular epithelial cells, to the glomerular basement membrane (GBM), and also to immune deposits. Type IV collagen was specifically identified as being modified by MDA adducts, using a variety of techniques. Collagenase pretreatment of GBM extracts indicated that the NC-1 domain of type IV collagen was a site of adduct formation. When LPO was inhibited by pretreatment of PHN rats with the antioxidant probucol, proteinuria was reduced by approximately 85%, and glomerular immunostaining for dialdehyde adducts was markedly reduced, even though the formation of immune deposits was not affected. By contrast, lowering of the serum cholesterol levels had no influence on the development of proteinuria. These findings are consistent with the premise that ROS-induced glomerular injury in PHN involves LPO and that this results not only in damage of cell membranes but in modification of type IV collagen in the GBM as well. The close temporal correlation of the occurrence of LPO with proteinuria and the ability of probucol to inhibit proteinuria support a causal role for LPO in the the alteration of the glomerular permselectivity which results in proteinuria.


Huge mucinous carcinoma of the breast in which doubling time was observed by computed tomography during 3 years without treatment.
Here we report the case of a 77-year-old woman with a huge cancer of the right breast for which size was measured on computed tomography in our hospital preoperatively and in other hospital 3 years earlier. During the 3-year untreated interval, the tumor grew from 4 cm to 13 cm in maximum diameter, and the tumor-volume doubling time (TVDT) was calculated as 209 days. The patient underwent mastectomy with axillary lymph node dissection, with the large skin defect covered by autologous skin graft. The pathological diagnosis was pure mucinous carcinoma (MC) of the breast with a low MIB-1 index, no vessel invasion, and no lymph node metastasis. Breast MC has been known to show a slow growth rate, but the TVDT of this current tumor was not markedly different from that of common breast cancers described in previous reports. This short TVDT notwithstanding the low aggressiveness may be due to abundant mucin occupying the majority of the tumor volume. To the best of our knowledge, no previous reports have provided accurate TVDTs for breast MC.


Complex behaviour of vacancy point-defects in SrRuO3 thin films.
The behaviour of point defects in thin, epitaxial films of the oxide electrode SrRuO3 was probed by means of diffusion measurements. Thin-film SrRuO3 was deposited by means of pulsed laser deposition (PLD) on (100) oriented, undoped single crystal SrTiO3 substrates. (16)O/(18)O exchange anneals were employed to probe the behavior of oxygen vacancies. Anneals were performed in the temperature range 850 ≤T/K≤ 1100 at an oxygen partial pressure of pO2 = 500 mbar. Samples were subsequently analyzed by means of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). The measured oxygen isotope penetration profiles comprised, surprisingly, two features. Oxygen tracer diffusion coefficients determined for thin-film SrRuO3 are amongst the lowest measured for nominally undoped perovskite-type oxides. The activation enthalpy of oxygen tracer diffusion was found to be ≈ 2 eV. Diffusion of Ti from the SrTiO3 substrates into the SrRuO3 thin films, probing the cation defects, was also observed in ToF-SIMS profiles; here, too, the diffusion profiles showed two features. The activation enthalpy of titanium diffusion was found to be ΔHDTi≈ 4 eV. We propose a model-cation sublattice equilibration-that accounts for the appearance of two features in both anion and cation diffusion profiles. We suggest that the observed complex behavior arises from the metastable defect structure of PLD thin films and the unusual defect structure of SrRuO3.


Peritoneal lesions caused by Enterobius vermicularis suspected to be metastases of ovarian malignancy.
Enterobius vermicularis, also known as pinworm, is a helminth that commonly causes intestinal parasitic infestation. E. vermicularis can also cause extraintestinal infestations. We report a case of lower abdominal pain and intermittent vaginal bleeding in a 45-year-old woman who was referred to our gynaecology department. On investigation, a transvaginal ultrasound showed a multilocular cyst in the left ovary, along with elevated levels of cancer antigen 125. Consequently, a laparoscopic salpingo-oophorectomy was performed. A biopsy of atypical peritoneal lesions revealed remains of E. vermicularis Peritoneal lesions are a rare complication of enterobiasis, and the diagnosis of this complication is usually delayed by limitations in diagnostic options. Although extraintestinal enterobiasis does not require treatment because it is the last stage of the parasitic cycle, primary intestinal infestation requires treatment with mebendazole.


Two- and three-dimensional computer graphic evaluation of the subacute spinal cord injury.
We have evaluated three-week-old compression lesions of the rat spinal cord using two-dimensional and three-dimensional morphometry, reconstruction, and visualization techniques. We offer a new computer assisted method to determine the number and density of macrophages within the spinal lesion using the macrophage specific monoclonal label ED1. We also provide quantitative information on pathological cyst formation and cavitation. This technique does not require: (1) subjective identification of the cell type, (2) human interaction with the data during the phase of quantification, and (3) can be applied to any sampling paradigm based on immunocytochemical labeling. Using novel algorithms based on solutions to 'correspondence' and 'branching' problems inherent in cross-sectional histological data, we provide three-dimensional reconstructions and visualizations of the macrophagic lesions and cysts imbedded within it. Our three-dimensional surface reconstructions can be interrogated to determine volumes and surface areas of structures within the data set. Using these methods we have learned that macrophage numbers approach the maximum density possible for such isodiametric cells (approximately 12 microm diameter) in the central lesion ranging from 4000-7000 cells per mm2 of lesion. At the time point studied, macrophage numbers would have peaked following the initial insult, and would not be expected to decline for several months. While the density of macrophages is highest in the region of most tissue damage, we show that the central regions of cavitated and cystic spinal parenchyma is not. We discuss how this density of cells may effect the secondary pathological responses of the spinal cord to injury.


Role of Cell-Intrinsic and Environmental Age-Related Changes in Altered Maintenance of Murine T Cells in Lymphoid Organs.
Age-related changes in primary lymphoid organs are well described. Less is known about age-related changes affecting peripheral lymphoid organs, although defects in old peripheral lymph nodes (pLNs) were recently described in both steady state and during viral infection. To address whether such pLN defects were intrinsic to old T cells or extrinsic (due to aging microenvironment), we employed heterochronic parabiosis. We found no age-related intrinsic or extrinsic barriers to T cell circulation and seeding of pLN, spleen, and bone marrow. However, heterochronic parabiosis failed to improve cellularity of old pLN, suggesting an environment-based limit on pLN cellularity. Furthermore, upon parabiosis, pLN of the adult partner exhibited reduced, old-like stromal and T cell cellularity, which was restored following separation of parabionts. Decay measurement of adult and old T cell subsets following separation of heterochronic parabionts delineated both T cell-intrinsic and environmental changes in T cell maintenance. Moreover, parabiotic separation revealed differences between CD4 and CD8 T cell subset maintenance with aging, the basis of which will require further investigation. Reasons for this asymmetric and subset-specific pattern of differential maintenance are discussed in light of possible age-related changes in lymph nodes as the key sites for peripheral T cell maintenance.


Anatomic three-dimensional model-assisted surgical planning for treatment of pediatric hip dislocation due to osteomyelitis.
Management of pediatric septic coxarthritis and osteomyelitis of the femur is challenging, and the sequelae of multiplanar hip joint deformity with instability are difficult to reconstruct. The inadequacy of a suitable device for fixing small bones during pediatric osteotomy is a hindrance to the correction of subluxated hip joints and deformed femurs in children. Two-dimensional axial images and three-dimensional (3D) virtual models representing the patient's individual anatomy are usually reserved for more complex cases of limb deformity. 3D printing technology can be used for preoperative planning of complex pediatric orthopedic surgery. However, there is a paucity of literature reports regarding the application of 3D-printed bone models for pediatric post-osteomyelitis deformity. We herein present a case of a 4-year-old boy who underwent treatment for post-osteomyelitis deformity. We performed corrective surgery with Pemberton osteotomy of the right hip, multilevel varus derotation osteotomy of the right femur, and immobilization with a hip spica cast. A 3D-printed bone model of this patient was used to simulate the surgery, determine the proper osteotomy sites, and choose the appropriate implant for the osteotomized bone. A satisfactory clinical outcome was achieved.


Tumor cell heterogeneity in multiple myeloma: antigenic, morphologic, and functional studies of cells from blood and bone marrow.
Tumor cells from six patients with immunoglobulin G (IgG) multiple myeloma were analyzed for surface antigens, cytoplasmic paraprotein, morphology, and response to various culture conditions. The tumor marker was the paraprotein idiotype. Low numbers of tumor cells were found in the blood of most of the patients. In some patients, the circulating tumor cells were solely B lymphocytes, whereas in other patients, they were lymphoid, lymphoplasmacytoid, and plasmacytoid. Dual surface antigen analysis of blood and bone marrow cells confirmed that the tumor may be composed of a spectrum of cell types. Thus, cells may range from surface-idiotype+,CD19+,CD20+, PCA-1-,cytoplasmic-idiotype- lymphocytes, to CD19-,PCA-1+,cytoplasmic-idiotype+ plasma cells that are surface-idiotype- or weakly surface-idiotype+. In one patient, some of the tumor cells co-expressed surface idiotype and CD10. The tumor B lymphocytes were activated in vitro to synthesize paraprotein by pokeweed mitogen (PWM), and by low molecular weight B cell growth factor (BCGF). In contrast, spontaneous synthesis of paraprotein by more mature tumor cells was inhibited by agents that also inhibit nonmyeloma plasma cells. These agents included PWM, gamma interferon, and phorbol ester. The results demonstrate that in multiple myeloma there exist different tumor cell types that are similar, by a variety of criteria, to normal B lineage cells at different stages of differentiation. Thus, further evidence is provided for the hypothesis of myeloma cell differentiation.


Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells.
Cobalt oxide nanoparticles (Co(3)O(4)NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co(3)O(4)NPs in human cells. We investigated the possible mechanisms of genotoxicity induced by Co(3)O(4)NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co(3)O(4)NPs and Co(2+) exposure. Co(3)O(4)NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co(3)O(4)NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co(3)O(4)NPs, whereas Co(2+) induced less change than Co(3)O(4)NPs but significantly more than control. Our results demonstrated that Co(3)O(4)NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress.


Core-perfluoroalkylated perylene diimides and naphthalene diimides: versatile synthesis, solubility, electrochemistry, and optical properties.
By a strategy featuring perfluoroalkylation of the highly soluble intermediates and their further efficient transformations to target compounds, a versatile synthesis of core-perfluoroalkylated perylene diimides (PDIs) and naphthalene diimides (NDIs) was developed, and PDIs perfluoroalkylated at 1-position or 1,6-positions and core-perfluoroalkylated NDIs were first obtained. By esterification, perfluoroalkylation, hydrolysis, and condensation with amine, 1-perfluorooctyl-PDIs (7b, 7c, and 7e), 1,7-bis(perfluorooctyl)-PDIs (8a-c and 8e-g), 1,6-bis(perfluorooctyl)-PDIs (8'e), a mixture of 1,7-bis(trifluoromethyl)-PDIs and 1,6-bis(trifluoromethyl)-PDIs (11b and 11'b, 11d and 11'd, in a ratio of 19:1), 2-perfluorooctyl-NDIs (20a-d), and 2,6-bis(perfluorooctyl)-NDIs (21a-21d) were efficiently synthesized. Five valuable intermediates--1-perfluorooctylperylene dianhydride (5), 1,7-bis(perfluorooctyl)perylene dianhydride (6) 1,6-bis(perfluorooctyl)perylene dianhydride (6'), 2-perfluorooctylnaphthalene dianhydride (18), and 2,6-bis(perfluorooctyl) naphthalene dianhydride (19)--were also obtained, and they can condense with many amines to produce PDIs containing different functional side chains on the imide nitrogen atoms. Solubility, electrochemistry, and optical properties of the above core-perfluoroalkylated PDIs and NDIs were investigated. Core-perfluoroalkylated 8e, 8f, 8'e, mixture of 11d and 11'd, 20b, and 20d with excellent solubility in common organic solvents are competitive as candidates as solution processable semiconductors. Core-perfluoroalkylated PDIs and NDIs with experimental LUMO energy of 4.04-4.34 eV demonstrate strong electron accepting ability. For core-perfluoroalkylated PDIs, the maximum absorptions display blue shifts of 6-18 nm and the maximum molar extinction coefficients decrease obviously relative to those of unsubstituted PDIs, and they inherit the strong fluorescence from the PDIs family, which makes them promising fluorescent dyes.


The viral Ki-ras gene must be expressed in the G2 phase if ts Kirsten sarcoma virus-infected NRK cells are to proliferate in serum-free medium.
NRK cells infected with a temperature-sensitive Kirsten sarcoma virus (ts371 KSV) are transformed at 36 degrees C, but are untransformed at 41 degrees C which inactivates the abnormally thermolabile oncogenic p21Ki product of the viral Ki-ras gene. At 41 degrees C, tsKSV-infected NRK cells were arrested in G0/G1 when incubated in serum-free medium, but could then be stimulated to transit G1, replicate DNA, and divide by adding serum at 41 degrees C or dropping the temperature to a p21-activating 36 degrees C without adding serum. When quiescent cells at 41 degrees C were stimulated to transit G1 in serum-free medium by activating p21 at 36 degrees C and then shifted back to the p21-inactivating 41 degrees C in the mid-S phase, they continued replicating DNA but could not transit G2. Reactivating p21 in the G2-arrested cells by once again lowering the temperature to 36 degrees C stimulated a rapid entry into mitosis. By contrast, while serum-stimulated quiescent G0 cells at 41 degrees C replicate DNA and divide, serum did not induce G2-arrested cells to enter mitosis, indicating that serum growth factors may trigger events in the G1 phase that ultimately determine G2 transit. These observations made with the viral ras product suggest that cellular ras proto-oncogene products have a role in G2 transit of normal cells.


Prostatic intraepithelial neoplasia: an overview.
Prostatic intraepithelial neoplasia (PIN) is the most established precursor of prostatic carcinoma. The presence of prominent nucleoli within an existing duct structure is an easy way to identify the disorder. Four main patterns of high-grade PIN (HGPIN) have been described: tufting, micropapillary, cribriform, and flat. In addition to exhibiting similar cytologic features, both HGPIN and prostatic carcinoma are associated with increased incidence and severity with age, and with high rates of occurrence in the peripheral zone of the prostate. HGPIN and prostate cancer share genetic and molecular markers as well, with PIN representing an intermediate stage between benign epithelium and invasive malignant carcinoma. The clinical significance of HGPIN is that it identifies patients at risk for malignancy. With the increased use of extended biopsy protocols, clinicians are more likely to identify HGPIN and less likely to miss concurrent carcinoma. Androgen deprivation therapy decreases the prevalence and extent of PIN, and may play a role in chemoprevention. Preliminary studies suggest that selective estrogen receptor modulators may also prevent the progression of HGPIN to prostate cancer.


KDM6A promotes hepatocellular carcinoma progression and dictates lenvatinib efficacy by upregulating FGFR4 expression.
Hepatocellular carcinoma (HCC) is one of the major causes of death from cancer and has a very poor prognosis with few effective therapeutic options. Despite the approval of lenvatinib for the treatment of patients suffering from advanced HCC, only a small number of patients can benefit from this targeted therapy. Diethylnitrosamine (DEN)-CCL4 mouse liver tumour and the xenograft tumour models were used to evaluate the function of KDM6A in HCC progression. The xenograft tumour model and HCC cell lines were used to evaluate the role of KDM6A in HCC drug sensitivity to lenvatinib. RNA-seq and ChIP assays were conducted for mechanical investigation. We revealed that KDM6A exhibited a significant upregulation in HCC tissues and was associated with an unfavourable prognosis. We further demonstrated that KDM6A knockdown remarkably suppressed HCC cell proliferation and migration in vitro. Moreover, hepatic Kdm6a loss also inhibited liver tumourigenesis in a mouse liver tumour model. Mechanistically, KDM6A loss downregulated the FGFR4 expression to suppress the PI3K-AKT-mTOR signalling pathway, leading to a glucose and lipid metabolism re-programming in HCC. KDM6A and FGFR4 levels were positively correlated in HCC specimens and mouse liver tumour tissues. Notably, KDM6A knockdown significantly inhibited the efficacy of lenvatinib therapy in HCC cells in vitro and in vivo. Our findings revealed that KDM6A promoted HCC progression by activating FGFR4 expression and may be an essential molecule for influencing the efficacy of lenvatinib in HCC therapy.


Cleidocranial dysplasia: molecular genetic analysis and phenotypic-based description of a Middle European patient group.
Cleidocranial dysplasia (CCD) (OMIM 119600) is a rare dysplasia of osseous and dental tissue. Characteristic features are typical facial and dental appearance plus morphologic anomalies. RUNX2 (OMIM 600211), the responsible gene for CCD, is considered to be a master gene for bone development and bone homeostasis. This study describes the genotype-phenotype correlation based on craniofacial features involving an interdisciplinary approach. Our patient cohort consisted of 31 CCD patients from 20 families; five patients from two families were unavailable for clinical examination. Since CCD mostly affects the craniofacial region, phenotypic characterization of each individual focused on craniofacial and dental aspects. After recording patient medical and family history, the phenotypic data was analyzed using homogeneity analysis (HOMALS), a statistical procedure for data reduction in categorical data analysis. The coding sequence of the RUNX2 gene was analyzed using PCR, direct sequencing, and restriction endonuclease digestion. Eight unpublished and four known heterozygous mutations in a total of 14/20 index patients (70%) were identified. In total, we detected 7 missense mutations, 5 frameshift mutations, and 2 nonsense mutations in 14 index patients (35%, 25%, 10%, respectively). The overall CCD phenotype varied from mild to fullblown expression. Using HOMALS, we were able to discriminate four groups of patients showing significant differences in phenotypic expressivity, thereby simplifying the grouping of our large patient cohort into clear distinguishable entities. Analysis of the mutation patterns revealed that mutational frequency and types of mutations found can be attributed to the gene's structure and function.


Effects of ferrous iron and molecular oxygen on chromium(VI) redox kinetics in the presence of aquifer solids.
The kinetics and stoichiometry of the reduction of hexavalent chromium (Cr(VI)) with ferrous iron (Fe(II)) were examined in systems with and without aquifer solids. Cr(VI) reduction was rapid in the absence of solids, but demonstrated slower and more complex kinetics in the presence of aquifer solids. The aquifer solids removed Fe(II) from solution and a portion of the reducing capacity of Fe(II) was transferred to the aquifer solids. The solid phases were then able to continue to remove Cr(VI). This suggests in situ treatment of Cr(VI) by Fe(II) injection would be feasible in the aquifer environment. In general, re-oxidation of reduced chromium by molecular oxygen was not observed in our systems over time periods of nearly 1 year, suggesting that the potential for chromium solubilization under these oxidizing conditions will be low. An empirical model was developed to describe the reduction kinetics of Cr(VI) in the presence of solids. The model assumes that the reaction is brought about by pseudo-species of iron that react instantaneously, rapidly and slowly with Cr(VI). A fourth pseudo-species is assumed to be non-reactive. Model coefficients were determined by non-linear regression. The model was able to describe observed concentrations of chromium well, but analysis of model errors indicated the potential existence of a distribution of species with different reaction rates rather than just three distinct species. Another model was developed to predict concentrations of different pseudo-species depending on the total amount of Fe(II) added and the amount of aquifer solids present. This model assumed that pseudo-species could result from intrinsic characteristics of the aquifer solids as well as being formed by addition of Fe(II), which could sorb to the aquifer solids.


Virus Satellites Drive Viral Evolution and Ecology.
Virus satellites are widespread subcellular entities, present both in eukaryotic and in prokaryotic cells. Their modus vivendi involves parasitism of the life cycle of their inducing helper viruses, which assures their transmission to a new host. However, the evolutionary and ecological implications of satellites on helper viruses remain unclear. Here, using staphylococcal pathogenicity islands (SaPIs) as a model of virus satellites, we experimentally show that helper viruses rapidly evolve resistance to their virus satellites, preventing SaPI proliferation, and SaPIs in turn can readily evolve to overcome phage resistance. Genomic analyses of both these experimentally evolved strains as well as naturally occurring bacteriophages suggest that the SaPIs drive the coexistence of multiple alleles of the phage-coded SaPI inducing genes, as well as sometimes selecting for the absence of the SaPI depressing genes. We report similar (accidental) evolution of resistance to SaPIs in laboratory phages used for Staphylococcus aureus typing and also obtain the same qualitative results in both experimental evolution and phylogenetic studies of Enterococcus faecalis phages and their satellites viruses. In summary, our results suggest that helper and satellite viruses undergo rapid coevolution, which is likely to play a key role in the evolution and ecology of the viruses as well as their prokaryotic hosts.


Variation in the amount of petrolatum preparation applied at patch testing.
The elicitation of a positive patch test reaction in a given individual depends upon the dose of the sensitizer applied, the patch test technique and the occlusion time. The dose is determined by the concentration and volume/amount of test preparation applied. If the same amount/volume of a test preparation is applied all the time with the same test technique (same area of skin) and occlusion time, it is appropriate to use concentration as a dose parameter. Most contact sensitizers are incorporated in petrolatum (pet.). With pet. as vehicle, it is impossible to repeatedly apply an exact volume/amount. This study was performed to investigate the inter- and intra-individual variation of pet. preparation applied at patch testing by 3 technicians. Weighing demonstrated that the 3 technicians had about the same precision in their pet. application. The investigation demonstrates that there is both an inter-individual (statistically significant) and intra-individual variation in the amounts of pet. applied at patch testing for the 3 technicians. Presently, there is no recommendation on what amount of pet. preparation to apply, which merits a decision to be taken based on thorough investigations on the appropriate volumes of pet. preparation to be applied in various patch test systems.


Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats.
Obesity was identified as a major risk factor for malignant diseases, but underlying mechanisms remain unclear. Natural killer (NK) cells, a pivotal aspect of innate immunity, are capable of identifying and killing virally infected and tumor cells. Previous studies have shown altered NK cell functions in obesity, and the current study aimed to investigate the relationship between altered NK cell functions and increased cancer risk in obesity. To induce obesity male F344-rats received a high-fat diet (34% fat) or a control diet (4% fat). Thereafter, syngeneic mammary adenocarcinoma cells (MADB106) or a vehicle were intravenously (i.v.) injected. 15 min after injection, half of each group of rats were killed, lungs removed and immunohistochemically stained. Numbers of NK cells, MADB106 cells and NK cell-tumor cell interactions were quantified. Twenty-one days after tumor-cell injection the other half group of rats was killed and lung metastases were counted and relative mRNA concentrations of different NK cell receptors were determined. After short-term MADB106-challenge, DIO fed animals showed significantly decreased NK cell numbers in the blood and NK cell-tumor cell interactions in the lung as compared to their control littermates. Twenty-one days after MADB106 injection, the lungs of the DIO fed rats showed significantly more lung metastases compared to control animals, accompanied by reduced relative mRNA concentrations of the activating NK cell receptor NKG2D. We conclude that induction of obesity in F344-rats leads to reduced lung NK cell function against tumor cells and results in significantly enhanced lung metastasis as compared to lean animals. It can be hypothesized that obesity-induced altered NK cell functions play an important role in cancer growth and metastasis.


Double incontinence as a first symptom of saddle embolism of the aorta leads to sudden paraplegia.
An aortic saddle embolus causing cauda equine syndrome followed by paraplegia is an exceedingly rare phenomenon in post-operative period in coronary artery bypass grafting. In non-CABG cases, reported documentation of neurological recovery from this event is even rarer. A 57-year-old male 8 days after uneventful OPCAP presented with severe lower extremity pain and sudden fecal and urinary incontinence, followed by the absence of pulsations in the lower limbs and paraplegia, during 20-minute period. He underwent immediate bilateral transfemoral embolectomy. The postoperative period was uneventful. The paraplegia recovered immediately after embolectomy and recovery from anesthesia. An angiography has been made to verify that a high origin of the great radicular artery above T12 level may be responsible for better recovery of paraplegia when its ostium obstructed by a saddle embolus relieved using embolectomy. Early surgical intervention in restoring the blood flow into the great radicular artery may prevent severe histological changes hitherto responsible for non-recovery from paraplegia in the earlier reports. Three unique characteristics of this article are as follows: 1) Occurrence of this complication in the post-operative period in off-pump CABG surgery; 2) Commencing of emboli with bizarre symptoms of double incontinence; 3) Combination of cauda equine syndrome and complete paralysis.


Preliminary SAR on indole-3-carbinol and related fragments reveals a novel anticancer lead compound against resistant glioblastoma cells.
The prognosis for glioblastoma patients is, at best, poor, with the median time of survival after diagnosis measured in months. As such, there is much need for the rapid development of potent and novel treatments. Herein, we report our preliminary findings on the SAR of a series of indole-3-carbinol and related fragments and reveal a potent lead with low micromolar activity against a particularly resistant glioblastoma cell culture, providing a new platform for future development of a new therapy in this area.


Ground-state electronic and magnetic properties of a mu3-oxo-bridged trinuclear Cu(II) complex: correlation to the native intermediate of the multicopper oxidases.
The ground-state electronic and magnetic properties of one of the possible structures of the trinuclear Cu(II) site in the native intermediate (NI) of the multicopper oxidases, the mu(3)-oxo-bridged structure, are evaluated using the C(3)-symmetric Cu(3)(II) complex, mu(3)O. mu(3)O is unique in that no ligand, other than the oxo, contributes to the exchange coupling. However, mu(3)O has a ferromagnetic ground state, inconsistent with that of NI. Therefore, two perturbations have been considered: protonation of the mu(3)-oxo ligand and relaxation of the mu(3)-oxo ligand into the Cu(3) plane. Notably, when the oxo ligand is sufficiently close to the Cu(3) plane (<0.3 Angstroms), the ground state of mu(3)O becomes antiferromagnetic and can be correlated to that of NI. In addition, the ferromagnetic (4)A ground state of mu(3)O is found from variable-temperature EPR to undergo a zero-field splitting (ZFS) of 2D = -5.0 cm(-1), which derives from the second-order anisotropic exchange. This allows evaluation of the sigma-to-pi excited-state exchange pathways and provides experimental evidence that the orbitally degenerate (2)E ground state of the antiferromagnetic mu(3)O would also undergo a ZFS by the first-order antisymmetric exchange that has the same physical origin as the anisotropic exchange. The important contribution of the mu(3)-oxo bridge to the ground-to-ground and ground-to-excited-state superexchange pathways that are responsible for the isotropic, antisymmetric, and anisotropic exchanges are discussed.


Monte Carlo simulation of the transmission of measles: beyond the mass action principle.
We present a Monte Carlo simulation of the transmission of measles within a population sample during its growing and equilibrium states by introducing two different vaccination schedules of one and two doses. We study the effects of the contact rate per unit time xi as well as the initial conditions on the persistence of the disease. We found a weak effect of the initial conditions while the disease persists when xi lies in the range 1/L-10/L (L being the latent period). Further comparison with existing data, prediction of future epidemics and other estimations of the vaccination efficiency are provided. Finally, we compare our approach to the models using the mass action principle in the first and another epidemic region and found the incidence independent of the number of susceptibles after the epidemic peak while it strongly fluctuates in its growing region. This method can be easily applied to other human, animal, and plant diseases and includes more complicated parameters.


[Physical training in the treatment of metabolic syndrome].
Increased daily physical activity is effective in the prevention of type 2 diabetes and several of the components in the metabolic syndrome. However, dedicated efforts in exercise training will also be effective in the treatment of the metabolic syndrome. The effect on glycaemic control is of the same order of magnitude as can be achieved by oral antidiabetic drugs. In addition, exercise (endurance and/or strength training) will also improve insulin resistance and body composition. The results are more doubtful for the dyslipidaemia and hypertension, but if the training is combined with an appropriate diet, these abnormalities are also correctable.


Integrin beta4 is involved in apoptotic signal transduction in endothelial cells.
To clarify the signal transduction in vascular endothelial cells (VEC) apoptosis induced by deprivation of FGF and serum, we investigated the function of integrin beta4 by using the monoclonal antibody (mAb) of this integrin. We added anti-beta 4 integrin mAb at the concentration of 5 microg/ml to the cells deprived of FGF and serum, apoptosis of these cells were completely inhibited 24 h after the treatment. Furthermore we plated the cells onto untreated bacterial culture plates on which the cells cannot adhere and spread in MCDB medium without FGF and serum; however, when anti-beta 4 integrin mAb was present at 5 microg/ml in the seeding medium, the cells rapidly adhered and spread. Our results first demonstrated that integrin beta4 participated in apoptotic signaling in VEC, and our findings indicate that hemidesmosome structures and keratin filament system might be important in regulation of apoptotic signaling.


Asialoglycoprotein receptor mediates the toxic effects of an asialofetuin-diphtheria toxin fragment A conjugate on cultured rat hepatocytes.
We have constructed a toxic hybrid protein that is recognized by asialoglycoprotein (ASGP) receptors of cultured rat hepatocytes. The conjugate consists of fragment A of diphtheria toxin (DTA) linked by a disulfide bond to asialofetuin (ASF). This conjugate is highly toxic, inhibiting protein synthesis in primary rat hepatocytes at concentrations as low as 10 pM. The ASF-DTA conjugate was 600 and 1800 times as toxic as diphtheria toxin and DTA, respectively, on primary rat hepatocytes. The ASGP receptor recognizes galactose-terminated proteins. We tested a series of glycoproteins for their ability to block the action of the ASF-DTA conjugate. Fetuin and orosomucoid, two glycoproteins with terminal sialic acid on their oligosaccharide chains, did not block the action of the conjugate. Their galactose-terminated asialo derivatives, ASF and asialoorosomucoid, as expected, did block the action of the conjugate. The N-acetylglucosaminyl-terminated derivative (asialogalactoorsomucoid) had no appreciable effect on the activity of the conjugate. We tested the ASF-DTA conjugate on six cell types; except for primary rat hepatocytes, none of them were affected by a high concentration (10 nM) of ASF-DTA conjugate. A fetuin-DTA conjugate was less toxic by a factor of 300 than the ASF-DTA conjugate and exerted its effects primarily through non-receptor-mediated mechanisms. The highly toxic ASF-DTA conjugate is cell-type specific, and its action is mediated by a well-characterized receptor, whose mechanism of receptor-ligand internalization has been extensively investigated.


Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women.
Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.


Understanding the Molecular and Cell Biological Mechanisms of Electrical Synapse Formation.
In this review article, we will describe the recent advances made towards understanding the molecular and cell biological mechanisms of electrical synapse formation. New evidence indicates that electrical synapses, which are gap junctions between neurons, can have complex molecular compositions including protein asymmetries across joined cells, diverse morphological arrangements, and overlooked similarities with other junctions, all of which indicate new potential roles in neurodevelopmental disease. Aquatic organisms, and in particular the vertebrate zebrafish, have proven to be excellent models for elucidating the molecular mechanisms of electrical synapse formation. Zebrafish will serve as our main exemplar throughout this review and will be compared with other model organisms. We highlight the known cell biological processes that build neuronal gap junctions and compare these with the assemblies of adherens junctions, tight junctions, non-neuronal gap junctions, and chemical synapses to explore the unknown frontiers remaining in our understanding of the critical and ubiquitous electrical synapse.


Improving suicide risk assessment in the emergency department through physician education and a suicide risk assessment prompt.
To determine the efficacy of two interventions on suicide risk assessment within emergency departments (EDs) on improving the documentation of suicide risk factors by emergency medicine and psychiatric physicians during suicide risk assessment. An educational intervention on suicide was provided to all emergency medicine and psychiatry physicians and was followed by the placement of a suicide risk assessment prompt within local EDs. The medical charts of all ED patients presenting with suicidal ideation or behaviours were reviewed immediately and six months after the interventions and compared to pre-intervention. Differences in the documentation of 40 biopsychosocial suicide risk factors between specialties and after the interventions were determined. The documentation of 34/40 (p ≤ 0.008) and 33/40 (p ≤ 0.009) suicide risk factors was significantly improved by emergency medicine and psychiatry physicians, respectively, after the interventions and maintained six months later. Immediately and six months after the interventions, the documentation of 8/40 (p ≤ 0.041) and 14/40 (p ≤ 0.048) suicide risk factors, respectively, significantly differed between specialties. This suggests that providing a brief educational intervention on suicide to emergency medicine and psychiatry physicians followed by placing a prompt for important, yet commonly undocumented risk factors within the ED is a low-cost and effective intervention for improving documentation of suicide risk assessments within the ED.


Diastereocontrolled synthesis of dinucleoside phosphorothioates using a novel class of activators, dialkyl(cyanomethyl)ammonium tetrafluoroborates.
A novel class of activators, dialkyl(cyanomethyl)ammonium tetrafluoroborates 1a-c, has been developed and applied to the condensations of diastereopure 5'-O-tert-butyldiphenylsilylthymidine 3'-cyclic phosphoramidites 3a-d with 3'-O-tert-butyldimethylsilylthymidine (4a). Among them, the condensation of 3a with 4a in the presence of 1a completed within 5 min and gave only one diastereoisomer of the corresponding phosphite 5a. After sulfurization and deprtection, almost diastereopure (Rp)-TpsT 7 was obtained (d.r. = 99:1). Next the 5'-O-(DMTr)nucleoside 3'-phosphoramidites 8a-d containing thymine, N6-benzoyladenine, N4-benzoylcytosine, and N2-phenylacetylguanine have been synthesized and allowed to condense with 3'-O-protected thymidine and 2'-deoxyadenosine. The 5'-O-DMTr group and the N-acyl groups of the nucleobases were compatible with the reaction conditions and the condensations completed quickly with excellent diastereoselectivity.


Ethical, Legal, and Social Challenges in the Development and Implementation of Disaster Telemedicine.
In recent years, advances in communications technology and market factors have led to a substantial expansion of telemedicine practice. One potential use of telemedicine is in disaster response, both as a resource for responders as well as a direct link to patients. The advantages of using telehealth to assist in disaster response are accompanied by important questions related to social impact, ethical implications, and regulatory oversight. A narrative review of several of these issues is presented here. The next steps in the development of a robust disaster telemedicine system will include the development of best practices and ethical guidelines agreed upon by all stakeholders, as well as the development of public-private partnerships geared at providing the highest quality disaster telemedicine to the greatest possible number of patients.


A regional, market oriented governance for disaster management: A new planning approach.
This paper proposes a regional competitive governance and management of response and recovery from disasters. It presents problems experienced in major disasters, analyzes the failures, and suggests how a competitive system that relies on private and volunteer regional leaders, personnel, and capital can improve preparation, response and recovery efforts over the existing government system. A Public Choice approach is adopted to explain why government often fails, and how regional governance may be socially more efficient than the existing federal- state-local funded and managed disaster system. The paper suggests that the federal role might change from both funding and supplying aid in disasters to merely funding disaster recovery efforts. When a disaster occurs, available businesses and government resources in the region can be utilized under a competitive system. These resources could replace existing federal and state inventories and emergency personnel. An independent regionally controlled and managed council, which also develops its own financial resources, and local volunteer leaders are key for success. The paper suggests a new planning method that utilizes the statistical Factor Analysis methodology to derive an efficient organizational and functional model to confront disasters.


Insulin stimulates the translation of ribosomal proteins and the transcription of rDNA in mouse myoblasts.
Insulin stimulates the translation of ribosomal protein (r-protein) mRNAs and the transcription of rDNA in mouse MM14DZ myoblasts. Analysis of the distribution of S16, L18, and L32 r-protein mRNAs in polysome gradients indicates that the increased translation of these mRNAs in insulin-treated myoblasts is due to the recruitment of mRNAs that were not previously being translated. In contrast, the translational efficiencies of beta-actin, c-myc, and p31 mRNAs are not affected by insulin. Hybridization analysis of RNA transcribed in nuclear run-on reactions indicates that insulin also stimulates the transcription of rDNA. Both the increases in r-protein translation and rDNA transcription occur coordinately and are maximal within 15 min of insulin treatment of myoblasts. However, insulin has no effect on the rate of cell division or the steady state levels of r-protein mRNAs. Surprisingly, after myoblasts differentiate into fibers, insulin does not affect the r-protein mRNA translation or rDNA transcription. These experiments indicate that the synthesis of the macromolecular components of ribosomes is tightly and coordinately controlled in myoblasts.


National Study of Adult Oral Health 2017-18: Study design and methods.
The National Study of Adult Oral Health (NSAOH) is Australia's third national oral examination survey of a representative sample of Australian adults. The study was undertaken primarily to describe levels of oral health in the population and to describe trends since the first survey, conducted in 1987-88. The aim of the study was to complete 7,200 examinations, necessitating approximately 15,200 completed interviews. Survey participants were selected using a multi-stage probability sampling design that began with the sampling of postcodes within states/territories in Australia. Individuals within selected postcodes were then selected by the Australian Government Department of Human Services (DHS) from the Medicare database. Following an initial opt-out period, participants were given the option to either complete the questionnaire online or to complete the questionnaire via a computer-assisted telephone interview. Participants were asked a series of questions about their oral health and dental service use and those who reported having one or more of their own natural teeth were invited to undergo a standardised oral examination. Examinations were conducted by state/territory dental practitioners who underwent prior training and calibration in survey procedures by the Australian Research Centre for Population Oral Health (ARCPOH), The University of Adelaide.


Physical therapy for vulvar vestibulitis syndrome: a retrospective study.
This retrospective study evaluated the effectiveness of physical therapy in relieving painful intercourse and improving sexual function in women diagnosed with vulvar vestibulitis. This syndrome is a frequent cause of premenopausal dyspareunia and is characterized by a sharp, burning pain located within and limited to the vulvar vestibule (vaginal entry) and elicited primarily via pressure applied to the area. Participants were 35 women with vulvar vestibulitis who took part in physical therapy treatment for an average of 7 sessions. We conducted telephone interviews to assess whether physical therapy or other subsequent treatments impacted on pain during intercourse and sexual functioning. Length of treatment follow up ranged from 2 to 44 months, with a mean of 16 months. Physical therapy yielded a complete or great improvement for 51.4% of participants, a moderate improvement for 20.0% of participants, and little to no improvement for the other 28.6%. Treatment resulted in a significant decrease in pain experienced both during intercourse and gynecological examinations; it also resulted in a significant increase in intercourse frequency and levels of sexual desire and arousal. Successful patients were significantly less educated than nonsuccessful patients. Findings demonstrate that physical therapy is a promising treatment modality for dyspareunia associated with vulvar vestibulitis.


Off-Label Use of a Double-Layer Micromesh Carotid Stent for Hybrid Treatment of Popliteal Artery Aneurism Complicated by Chronic Distal Embolization.
We report our initial experience in off-label use of the double-layer micromesh (DLM) Roadsaver® stent for the hybrid treatment of a fusiform popliteal artery aneurism complicated by distal embolization and chronic limb threatening ischemia in a COVID-19-positive young male. A 36-year-old male patient was admitted with chronic limb threatening ischemia of the left lower limb. The duplex ultrasound and computer tomography angiography (CTA) demonstrated a fusiform popliteal artery aneurism with a maximal diameter of 14 mm and distal occlusion of peroneal and both tibial arteries. Urgent hybrid intervention was performed, starting with an open thrombectomy from the distal posterior tibial artery via a retromalleolar access followed by percutaneous deployment of the DLM Roadsaver® stent (Terumo, Tokyo, Japan) for the exclusion of the popliteal artery aneurism. The flow diverting effect was observed immediately with contrast stagnation in the asymmetrical part of the aneurism sac (grade C2 of the O'Kelly-Marotta flow diversion scale). The procedure was uneventful, with the regaining of an adequate foot perfusion and palpable pulse at the posterior tibial artery. On the 2nd postoperative day, the patient was diagnosed with a symptomatic form of COVID-19 infection and transferred to a dedicated facility. At a one-month follow-up, the patient had no symptoms of limb ischemia and CTA showed complete thrombosis of the aneurism sac, absence of endoleaks, and patency of the treated arterial segment. This case demonstrates the possibility of off-label use of the DLM Roadsaver® stent for hybrid treatment of popliteal artery aneurism complicated by distal embolization and critical limb ischemia.


Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis).
Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process.


Immunosuppression-enhancing effect of the administration of allogeneic canine adipose-derived mesenchymal stem cells (cA-MSCs) compared with autologous cA-MSCs in vitro.
Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive (IDO, PTGS2, and PTGES), inflammatory (IL6 and IL10), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.


Efficacy of antifungal agents in the cornea. IV. Amphotericin B methyl ester.
Quantitative mycologic techniques were used to evaluate the efficacy of topical amphotericin B methyl ester in two models of yeast infection in rabbit eyes. Doses of 1%, 0.5%, and 0.15% were used in a model of superficial Candida albicans infection. The 1% dose of drug was highly efficacious, abolishing the disease after 2 days of treatment. With doses of 0.5% and 0.15%, decreasing efficacy was observed. Antifungal activity did not deteriorate when 1% prednisolone acetate was administered concomitantly with the 1% dose. In a model of deep stromal infection, the administration of topical 1% amphotericin B methyl ester was highly efficacious when the corneal epithelium was absent. Even in corneas with intact epithelium, a reduced though still significant effect was noted.


[Effectiveness comparison between two kinds of procedures for treatment of totally degloved hand].
To compare the effectiveness between toe transfer combined with an abdominal flap and bag-shaped abdominal flap for treatment of totally degloved hand. Between January 2005 and January 2012, 18 patients with totally degloved hand were treated by two kinds of techniques. Those patients were divided into 2 groups according to the technique. The bag-shaped abdominal flap was used in 8 cases (group A), and toe transfer with a dorsal is pedis skin flap combined with abdominal S-shaped tile-joint subdermal vascular network flaps was performed in 10 cases (group B). There was no significant difference in gender, age, injury cause, injury degree, and interval between injury and operation between 2 groups (P > 0.05). The static two-point discrimination (s2PD), grip power of the reconstructed hand, time of returning to work, and active total range of motion (ROM) of the operated finger were compared between 2 groups to assess the effectiveness. All flaps and skin grafts survived in 2 groups. One flap suffered vascular crisis at 2 days after operation and survived after surgical exploration in group B. All patients were followed up 12-24 months (mean, 16 months). At last follow-up, group B showed a better recovery of s2PD of the thumb and ROM, and shorter time of returning to work than group A (P < 0.05), but no significant difference was found in grip power of the reconstructed hand and s2PD of the other fingers between 2 groups (P > 0.05). The technique of toe transfer combined with an abdominal flap is better than traditional bag-shaped abdominal flap with the advantages of easy dissection, less time of operation, and satisfactory functional recovery.


An in vivo porcine evaluation of the safety, bioavailability, and tissue penetration of a ketorolac drug-eluting ureteral stent designed to improve comfort.
Ureteral stents often cause significant patient morbidity that can be difficult to treat. Drug-eluting stent technology allows the local delivery of a drug. Our previous work demonstrated that ketorolac instilled intravesically at the time of ureteral stent insertion significantly decreased flank pain compared with controls. We sought to determine the safety of a novel ketorolac-eluting ureteral stent. A total of 92 Yorkshire pigs were randomized to 1 of 5 groups. The oral control group consisted of 12 animals with transurethrally inserted control ureteral stents and 5 days of oral ketorolac. Twenty animals in each of the remaining groups received a control stent, or 15%, 13%, or 7% ketorolac-loaded stents. Ketorolac levels were measured in plasma, urine, and tissue sampled from ureters, bladder, kidneys, and liver using high performance liquid chromatography. Necropsies were performed to evaluate tissue pathology. The majority of ketorolac was released within the first 30 days. The highest levels of ketorolac in plasma, kidney, and liver occurred in the oral control group. The highest levels of ketorolac found in ureteral and bladder tissues occurred in the ketorolac-stent groups in a dose-dependent fashion. No adverse events were noted in any of the ketorolac-stent groups. Gastric ulcerations were identified only in the oral control group. No abnormalities were identified in any other internal organs in any group. The use of ketorolac-eluting ureteral stents has proven to be safe in a porcine model. The ketorolac-stent group had less than 12% of the ketorolac concentration in plasma, kidney, and liver tissues compared with the oral ketorolac group. Ureteral tissues displayed the highest levels of ketorolac. Clinical studies are needed to determine if ketorolac-elution reduces stent symptoms.


Individual NK cell clones lyse both tumor cell targets and herpes simplex virus-infected fibroblasts in the absence of interferon.
The target specificity of natural killer (NK) cells for either tumor cells or virus-infected cells has been investigated. Lymphocyte clones with the surface phenotype of NK cells (CD3-, CD16+) were obtained by limiting dilution of peripheral blood mononuclear cells stimulated with PHA, Herpes simplex virus type 1 (HSV-1), or Varicella-Zoster antigens. Clones were maintained in media with recombinant interleukin 2 (IL-2). Both NK-sensitive (K562 cells) and NK-resistant (Raji cells) targets were lysed by three cloned lines of NK cells. The ability to lyse NK-resistant target cells was largely lost when the cloned lymphocytes were cultured overnight in the absence of IL-2. Effector cells from all three clones were also capable of specifically lysing HSV-1 infected human fibroblasts in comparison with uninfected fibroblasts. We also showed that lysis of HSV-1 infected targets by NK cloned cells was independent of interferons in the culture system.


Biochemical, immunological and genetic studies in leprosy. I. Changes in serum lactate dehydrogenase isoenzymes, creatine phosphokinase and aldolase activity in different forms of leprosy.
Serum lactate dehydrogenase isoenzymes, creatine phosphokinase and aldolase activity were determined in healthy control subjects and in lepromatous and tuberculoid leprosy patients from Ethiopia. Sera from lepromatous patients showed a higher total LDH activity compared with control subject. The values for tuberculoid leprosy patients were similar to those of controls. Sera from normal healthy controls showed a higher proportion of LDH-H form (72%) while lepromatous leprosy patient's sera exhibited a higher proportion of LDH-M form (55%). Tuberculoid leprosy patients showed a pattern similar to that of healthy controls. A possible significance of these observations is discussed. No significant variations were observed in fructose-1,6-diphosphate aldolase activity within the different types of disease and controls. Although creatine phosphokinase levels in different types of leprosy decreased significantly from those of normal healthy, it falls within the reported variation of the activity in normal sera.


Trans fatty acids, lipoproteins, and coronary risk.
Most dietary fatty acids contain at least one double bond, which is usually in the cis configuration. However, biohydrogenation in the rumen of cows and sheep, or catalytic hydrogenation of vegetable oils in the food industries, will convert some of the cis double bonds to the trans configuration. Trans fatty acid intake in western Europe and North America probably ranges from 5 to 15 g/day. Major dietary sources are frying fats used in industrial food preparation, margarines, and other spreads. In the past, margarines contained up to 50% trans fatty acids; however, these are now being phased out. Trans fatty acids raise serum low density lipoprotein (LDL) cholesterol and lower high density lipoprotein (HDL) cholesterol in humans when substituted for cis unsaturated fatty acids in the diet. These effects may be mediated by the cholesteryl ester transfer protein. Trans fatty acids also increase lipoprotein (a) levels relative to other fatty acids. The effects of trans fatty acids on the risk profile for coronary heart disease are thus unfavorable, and labels of food products should state the trans fatty acid content.


An insight into the complex prion-prion interaction network in the budding yeast Saccharomyces cerevisiae.
The budding yeast Saccharomyces cerevisiae is a valuable model system for studying prion-prion interactions as it contains multiple prion proteins. A recent study from our laboratory showed that the existence of Swi1 prion ([SWI(+)]) and overproduction of Swi1 can have strong impacts on the formation of 2 other extensively studied yeast prions, [PSI(+)] and [PIN(+)] ([RNQ(+)]) (Genetics, Vol. 197, 685-700). We showed that a single yeast cell is capable of harboring at least 3 heterologous prion elements and these prions can influence each other's appearance positively and/or negatively. We also showed that during the de novo [PSI(+)] formation process upon Sup35 overproduction, the aggregation patterns of a preexisting inducer ([RNQ(+)] or [SWI(+)]) can undergo significant remodeling from stably transmitted dot-shaped aggregates to aggregates that co-localize with the newly formed Sup35 aggregates that are ring/ribbon/rod- shaped. Such co-localization disappears once the newly formed [PSI(+)] prion stabilizes. Our finding provides strong evidence supporting the "cross-seeding" model for prion-prion interactions and confirms earlier reports that the interactions among different prions and their prion proteins mostly occur at the initiation stages of prionogenesis. Our results also highlight a complex prion interaction network in yeast. We believe that elucidating the mechanism underlying the yeast prion-prion interaction network will not only provide insight into the process of prion de novo generation and propagation in yeast but also shed light on the mechanisms that govern protein misfolding, aggregation, and amyloidogenesis in higher eukaryotes.


Short-hairpin Mediated Myostatin Knockdown Resulted in Altered Expression of Myogenic Regulatory Factors with Enhanced Myoblast Proliferation in Fetal Myoblast Cells of Goats.
Myostatin (MSTN) is a well-known negative regulator of skeletal muscle development. Reduced expression due to natural mutations in the coding region and knockout as well as knockdown of MSTN results in an increase in the muscle mass. In the present study, we demonstrated as high as 60 and 52% downregulation (p < 0.01) of MSTN mRNA and protein in the primary fetal myoblast cells of goats using synthetic shRNAs (n = 3), without any interferon response. We, for the first time, evaluated the effect of MSTN knockdown on the expression of MRFs (namely, MyoD, Myf5), follistatin (FST), and IGFs (IGF-1 & IGF-2) in goat myoblast cells. MSTN knockdown caused an upregulation (p < 0.05) of MyoD and downregulation (p < 0.01) of MYf5 and FST expression. Moreover, we report up to ∼four fold (p < 0.001) enhanced proliferation in myoblasts after four days of culture. The anti-MSTN shRNA demonstrated in the present study could be used for the production of transgenic goats to increase the muscle mass.


[Infectious disease doctors also contract travellers' diarrhoea].
Acute infectious diarrhoea is common in travellers. The aim of this study was to examine the incidence of travellers' diarrhoea in a group of Danish doctors and to identify exposures that may confer protective benefits. A total of 19 Danish infectious disease doctors, pediatricians and clinical microbiologists received a questionnaire regarding symptoms of infectious diarrhoea after a journey to Myanmar. The association between exposure and outcome was calculated as a relative risk. The occurence of travellers' diarrhoea was independent of medical specialty and age. Doxycycline prophylaxis was a significant protective factor and high intake of yogurt seemed also to confer protection, albeit not significantly. No protective benefits were found from avoidance of ice cubes, raw salad or the use of hand sanitizer. Self-medication with antibiotics was associated with female sex, high age, previous travel experience, employment in the eastern part of Denmark and medical specialty other than infectious diseases, although not significant. Infectious disease doctors have a similar incidence of travellers' diarrhoea as others. Only a few intended to use common travel advice regarding food and drinks and no effect was shown. The reduced risk conferred by yogurt can be caused by the effect of live probiotics on diarrhoea pathogenesis. The reasons why the use of antibiotics was associated with sex, employment region and medical specialty are unaccounted for and should be interpreted with caution because of lack of statistical significance. not relevant. not relevant.


Mammalian calcitonin cells: retrospect and prospect.
In this review we aim to provide an overview of the published reports on the morphology, position, population, distribution and origin of calcitonin cells. Also, we have included a brief historical note and the experimental studies which demonstrate the effects on calcitonin cell function.


Robotic-assisted laparoscopy is a feasible method for resection of deep infiltrating endometriosis, especially in the rectosigmoid area.
This study aimed to compare outcomes of mini-invasive surgical treatment of endometriosis, especially conventional laparoscopy with robotic-assisted laparoscopy, and to evaluate the quality of life. One hundred three consecutive patients with endometriosis who had surgery from 2014 to 2017 owing to an indication of pain were enrolled in this retrospective study. The majority (n = 77, 75%) of patients underwent conventional laparoscopy and 18 (17%) had robotic-assisted laparoscopy. The quality of life was postoperatively assessed with a questionnaire. The rates of parametrectomy (76% vs. 45%,) and rectovaginal resection (28% vs. 4%) were significantly higher in robotic-assisted laparoscopy than in laparoscopy. Additionally, the rate of bowel operations (50% vs. 17%), especially the shaving technique, was higher in robotic-assisted laparoscopy surgery than in laparoscopy (39% vs. 8%). There was no difference in the rate of postoperative complications between laparoscopy and robotic-assisted laparoscopy. Most (91%) of the patients who answered the questionnaire felt that surgical treatment had relieved their pain. In the laparoscopic and robotic-assisted groups, 88% of respondents felt that their quality of life had improved after surgery. This study suggests that robotic-assisted laparoscopy is a feasible method to resect deep infiltrating endometriosis, especially in the rectosigmoid area.


Smoking-attributable morbidity: acute care hospital diagnoses and days of treatment in Canada, 2002.
Smoking is one of the most important risk factors for burden of disease. Our objective was to estimate the number of hospital diagnoses and days of treatment attributable to smoking for Canada, 2002. Distribution of exposure was taken from a major national survey of Canada, the Canadian Community Health Survey. For chronic diseases, risk relations were taken from the published literature and combined with exposure to calculate age- and sex-specific smoking-attributable fractions (SAFs). For fire deaths, SAFs were taken directly from available statistics. Information on morbidity, with cause of illness coded according to the International Classification of Diseases version 10, was obtained from the Canadian Institute for Health Information. For Canada in 2002, 339,179 of all hospital diagnoses were estimated to be attributable to smoking and 2,210,155 acute care hospital days. Ischaemic heart disease was the largest single category in terms of hospital days accounting for 21 percent, followed by lung cancer at 9 percent. Smoking-attributable acute care hospital days cost over $2.5 billion in Canada in 2002. Since the last major project produced estimates of this type, the rate of hospital days per 100,000 population has decreased by 33.8 percent. Several possible factors may have contributed to the decline in the rate of smoking-attributable hospital days: a drop in smoking prevalence, a decline in overall hospital days, and a shift in distribution of disease categories. Smoking remains a significant health, social, and economic burden in Canada.


Update on DWI for Breast Cancer Diagnosis and Treatment Monitoring.
DWI is a noncontrast MRI technique that measures the diffusion of water molecules within biologic tissue. DWI is increasingly incorporated into routine breast MRI examinations. Currently, the main applications of DWI are breast cancer detection and characterization, prognostication, and the prediction of treatment response to neoadjuvant chemotherapy. In addition, DWI is promising as a noncontrast MRI alternative for breast cancer screening. Problems with suboptimal resolution and image quality have restricted the mainstream use of DWI for breast imaging, but these shortcomings are being addressed through several technologic advancements. In this article, we present an up-to-date review on the use of DWI for breast cancer imaging, including a summary of the clinical literature and recommendations for future use.


Vein size in intact and hysterectomized mice during the estrous cycle and pregnancy.
The diameters of the ovarian, uterine, and femoral veins and the inferior vena cava were measured during stages of the estrous cycle in intact and hysterectomized mice and at intervals during pregnancy in mice with embryos in both uterine horns or in only the left horn. At metestrus I vein sizes were the least and were not significantly different in intact and hysterectomized mice. Ovarian and uterine veins showed the same or increased diameters at other stages of the cycle; veins enlarged progressively during pregnancy in intact mice. Non-gravid uterine horns showed little size increase as compared to gravid horns. Increases in vein diameter appeared to be correlated with local production of reproductive hormones. Evidence for transuterine migration of embryos was observed in 21 of 53 mice in which one uterine tube had been ligated or one ovary had been removed.


Protect children from EMF.
The twenty-first century is marked with aggressive development of the wireless communications (satellite, mobile phones, Internet, Wi-Fi). In addition to thousand of satellites that deliver radio and TV signals, large satellite and base station networks secure intensive instant delivery of audio and video information. It is fair to say that that the entire civilization, both biosphere and mankind are exposed to continuous exposure of multitude of radiofrequency (RF) signals. It should be taken into account that the entire world population is exposed to exponentially increasing RF radiation from base stations and satellite antennas. While several years ago the potential hazard was connected with placement of mobile phones close to human head, today "smart phones" represent small, but powerful computers continuously receiving audio and video data. The largest group of users is the children and teenagers who "need" to communicate nearly 24 h a day. This is even more important because cell phones and tablets may be seen in the hands of children as little as two years in age. There is no way to assess and predict the potential damages of children brain, vision and hearing under exposure to RF radiation. The WHO precautionary principle and IARC classification must be applied in discussing the potential hazard of the use of today's and tomorrow's communication devices.


Prognostic role of intermountain risk score (IMRS) in intensive care unit patients with a diagnosis of COVID-19.
In this study, we aimed to assess the predictive value of Intermountain Risk Score (IMRS) in intensive care unit (ICU) patients with COVID-19. Our retrospective study included the data of 194 patients who were admitted to the COVID-19 ICU of a tertiary care center. COVID-19 diagnoses were made by a positive result from a real-time reverse-transcriptase (RT) polymerase chain reaction (PCR) assay of nasal and pharyngeal swab specimens. Patients who had negative RT-PCR results or who were not admitted to ICU and patients under 18 years old were excluded from the study. Complete blood count, biochemistry panel, and blood gas analysis results were gathered and compiled. 194 ICU patients with COVID-19 (PCR positive) were included in the study. The patients were divided into two groups according to IMRS (if IMRS was <15 in women and <17 in men, patients were included in the non-high-risk group, while patients with IMRS ≥15 in women and ≥17 in men were defined as a high-risk group). Multivariate regression analysis was performed to predict in-hospital mortality. The IMRS [OR: 1.17 (1.08-1.27) p<0.001)] was found to predict in-hospital mortality. In this study, we showed that the IMRS score at admission can predict in-hospital mortality in intensive care unit patients with a diagnosis of COVID-19.


Development of a novel approach to detect damage in concrete structures with millimeter wave radar assessment system.
Nonintrusive damage assessment of concrete structures is evolving using newer technological interventions. Researchers are using different assessment techniques having their intrinsic limitations. A few are partially destructive, whereas others only provide qualitative information about the damages. Therefore, there is a need for a method using high-resolution imaging techniques for the assessment of exact damages and their depth along with intensity. Millimeter wave may be one of the good options for damage assessment. It is an efficient technique used in imaging applications due to its high resolution and effective penetration. Therefore, a novel millimeter wave assessment method is used in this study as a nondestructive post-fire damage test of concrete based civil engineering structures. An active millimeter wave radar system of 55-65 GHz has been used to measure the complex relative permittivity of concrete cube specimens for evaluation of damages caused by fire. In this study, fire damaged and control concrete cube specimens of 150 mm size were used for the measurement. The results were compared with the existing technique of ultrasonic pulse velocity, and it was found to be in good agreement.


Numerical analysis of thermal response of tissues subjected to high intensity focused ultrasound.
The present work is concerned with the numerical investigation of the thermal response of tissue-mimicking biological phantom(s) subjected to high intensity focused ultrasound (HIFU). Simulations have been performed on the 3-dimensional physical domain for two-layered as well as multi-layered medium consisting of water and liver tissue. Local pressure distribution within the body of the phantom has been calculated by solving the complete full-wave nonlinear form of Westervelt equation. The solution of the pressure wave equation has been coupled with Pennes bioheat transfer equation to determine the full field temperature distribution. Results in the form of pressure fields, temperature distributions and the corresponding thermal dosage in the targeted region of the tissue domain have been presented. Magnitudes of the maximum pressure (and hence the resultant temperature levels) in the focal region as obtained using the nonlinear form of Westervelt equation are found to be significantly higher than that determined based on the linear form of the equation. Compared to water, wherein the acoustic intensity is maximum, the addition of sub-layers of skin, fat, and muscle into water resulted in the reduction of the peak intensity and also shifted the intensity profiles along the direction of propagation of the acoustic waves. However, addition of liver tissue into water led to the shifting of intensity profile in the opposite direction i.e., towards the transducer. The results further reveal that due to the dependence of attenuation coefficient on the source frequency, the temperature at the focal region increases with an increase in the transducer frequency. The work is further extended from single lesion to multiple lesion generation through controlled movement of the transducer and the resultant transient full field temperature distribution has been presented. The concerned observations highlight the need of optimizing the thermal energy for each lesion, the inter spatial distance between different lesions and the delay time so as to ensure minimal thermal damage to the surrounding healthy cells as well as to reduce the total treatment duration.


Analysis of growth rate of pediatric kidneys transplanted into juveniles or adults.
Estimation of renal length was carried out during radionuclide function studies, in cases of pediatric kidneys transplanted into adolescents or adults. In all 24 cases of single kidney transplants, the kidneys eventually increased in size, but at varying rates. From 5 cases with repeat studies close in time, and shortly after transplantation, an apparent maximal growth rate was estimated. In 3 pairs of dual renal transplants, with both kidneys surviving, marked differences in growth of each member of the pair was noted. The present initial description, of rates of change in size of the transplanted pediatric kidneys, may serve as a baseline from which to sort out the contributions of pre- and post-transplant factors.


[Fine-needle biopsy of the kidneys].
The methods, indications, results, and complications in fine-needle puncture of the kidneys are discussed, with particular attention to cysts that have an atypical appearance in tomographic procedures. The problems of percutaneous cyst treatment and the possibilities of abscess therapy by fine-needle puncture are presented. The limited indications of using this method in solid kidneys tumors are defined, and antegrade pyelography and the differentiation of perirenal processes are discussed.


Sustainable health systems: addressing three key areas.
In the modern context sustainable health systems are being developed using the newest technological and communication technologies. This is proving to be a great success for the growth of Health Informatics and healthcare improvement. However this revolution is not being reached by a lot of the world population. This paper will address the importance of closing the Digital Divide, Empowerment of health consumers and the importance of converging communications. Key areas in the development of a truly sustainable health system.


Vaccine design reaches the atomic level.
The genetic diversity of pathogens presents a challenge to the development of broadly effective vaccines. In this issue, Scarselli et al. combine atomic-level structural information with genomics and classical vaccinology to design a single immunogen that elicits protective immunity against more than 300 natural variants of the bacterial pathogen meningococcus B. This accomplishment provides a glimpse of the power of structure-based vaccine design to create immunogens capable of eliciting protective responses against genetically diverse pathogens.


Concavity of the posterior surface of the temporomandibular condyle: clinical cases and autopsy correlation.
To elucidate the significance of the radiographic finding of a concavity of the posterior surface of the temporomandibular condyle. Three clinical cases with a concavity were followed up clinically and radiographically. A total of 39 temporomandibular joint (TMJ) autopsy specimens were examined by corrected sagittal tomography and seven condyles with a concavity of the posterior surface found. They were analysed microscopically together with three joints with a normal, rounded condyle. At follow-up tomography, two of the clinical cases revealed no change while the third patient had erosive changes after 7 months. The microscopic findings of the autopsy specimens varied. The articular cartilage in three of the seven joints with a concavity was similar to that in the normal condyles. The outer surface of the articular cartilage was sometimes uneven and the cartilage thickened, with an irregular junction between the articular cartilage and subchondral bone. In three joints the cartilage in the concavity had been replaced by granulation tissue. All seven joints had increased cellular activity in the concavity. The radiographic finding of a concavity in the posterior surface of the condyle is not specific. When small and well-defined it is indicative of remodelling and of osteoarthrosis when larger and with a diffuse outline.


Sulfone syndrome in a patient receiving steroids for pemphigus.
A male patient who was being treated with oral prednisone for erosive mucocutaneous pemphigus lesions developed fever, jaundice, a rash, and anemia within 2 wk of starting dapsone therapy. These signs are typical of the sulfone syndrome, which is a potentially fatal condition due to dapsone hypersensitivity. The incidence of sulfone syndrome is increasing in frequency but has not previously been reported in pemphigus. This patient developed the syndrome early and while on oral steroids, which are sometimes used as a treatment for the sulfone syndrome, and without any evidence of a hypersensitivity reaction. Physicians should be aware of the potentially fatal sulfone syndrome in patients who are on dapsone therapy and who have abnormal liver tests, fever, and a rash.


Imprinted survival genes preclude loss of heterozygosity of chromosome 7 in cancer cells.
The genomes of a wide range of cancers, including colon, breast, and thyroid cancers, frequently show copy number gains of chromosome 7 and rarely show loss of heterozygosity. The molecular basis for this phenomenon is unknown. Strikingly, oncocytic follicular thyroid carcinomas can display an extreme genomic profile, with homozygosity of all chromosomes except for chromosome 7. The observation that homozygosity of chromosome 7 is never observed suggests that retention of heterozygosity is essential for cells. We hypothesized that cell survival genes are genetically imprinted on either of two copies of chromosome 7, which thwarts loss of heterozygosity at this chromosome in cancer cells. By employing a DNA methylation screen and gene expression analysis, we identified six imprinted genes that force retention of heterozygosity on chromosome 7. Subsequent knockdown of gene expression showed that CALCR, COPG2, GRB10, KLF14, MEST, and PEG10 were essential for cancer cell survival, resulting in reduced cell proliferation, G1 -phase arrest, and increased apoptosis. We propose that imprinted cell survival genes provide a genetic basis for retention of chromosome 7 heterozygosity in cancer cells. The monoallelically expressed cell survival genes identified in this study, and the cellular pathways that they are involved in, offer new therapeutic targets for the treatment of tumours showing retention of heterozygosity on chromosome 7. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Effect of coadministered salicylamide on terbutaline metabolism in rats.
Concomitant oral administration of salicylamide (200 mg/kg) and 3H-terbutaline (1 mg/kg) to rats with ligated bile ducts decreased absorption of terbutaline from the gut from 73 to 56% as measured by urinary excretion of radioactivity in 48 hr. No increase in the fraction of terbutaline excreted unchanged was observed, suggesting that salicylamide does not substantially inhibit the conjugation of terbutaline with glucuronic acid. An increase in the fraction of terbutaline excreted unchanged observed in normal animals may result from enhanced excretion of terbutaline glucuronide into bile rather than from inhibition of conjugation.


Alcohol, conflict, and aggression in intimate relationships: A dyadic approach.
Intimate partner aggression (IPA) is a critical public health problem that requires clear and testable etiological models that may translate into effective interventions. While alcohol intoxication and a pattern of heavy alcohol consumption are robust correlates of IPA perpetration, there has been limited research that examines this association from a dyadic perspective. In the present review, we discuss compelling reasons for understanding dyadic factors that assist our understanding of alcohol-facilitated IPA, review the relatively small number of studies that have investigated such factors, and provide a theoretical and methodological framework for researchers to conceptualize how to model alcohol-facilitated IPA from a dyadic framework.


The Bain anaesthetic system. An assessment during controlled ventilation.
The Bain anaesthetic breathing system-a modified Mapleson 'D' circuit10-had been evaluated during anaesthesia using controlled ventilation. Results obtained from over 140 patients show that a highly predictable PaCO2 may be obtained by adjusting the fresh gas inflow according to body weight in patients weighing over 40 kg (mean PaCO2 at a fresh gas inflow of 70 ml/kg/minute=40.8 mmHg; mean PaCO2 at a fresh gas inflow of 100 ml/kg/minute=34.3 mmHg). The circuit is long enough to provide flexibility but may even be doubled in length without affecting performance. Simple lung ventilators delivering air or oxygen may be used satisfactorily as anaesthetic ventilators for patients of all ages. In addition, the circuit is lightweight, disposable but re-usable, facilitates pollution control and is easily used as an independent resuscitator. It is suggested that it may qualify as a universal breathing system.


A Clinical Quantitative Evaluation of Hepatobiliary Transport of [11C]Dehydropravastatin in Humans Using Positron Emission Tomography.
Various positron emission tomography (PET) probes have been developed to assess in vivo activities in humans of drug transporters, which aid in the prediction of pharmacokinetic properties of drugs and the impact of drug-drug interactions. We developed a new PET probe, sodium (3R, 5R)-3, 5-dihydroxy-7-((1S, 2S, 6S, 8S)-6-hydroxy-2-methyl-8- ((1-[11C]-(E)-2-methyl-but-2-enoyl) oxy) -1, 2, 6, 7, 8, 8a-hexahydronaphthalen-1-yl) heptanoate ([11C]DPV), and demonstrated its usefulness for the quantitative investigation of Oatps (gene symbol SLCO) and Mrp2 (gene symbol ABCC2) in rats. To further analyze the species differences and verify the pharmacokinetic parameters in humans, serial PET scanning of the abdominal region with [11C]DPV was performed in six healthy volunteers with and without an OATP1Bs and MRP2 inhibitor, rifampicin (600 mg, oral), in a crossover fashion. After intravenous injection, [11C]DPV rapidly distributed to the liver and kidney followed by secretion into the bile and urine. Rifampicin significantly reduced the liver distribution of [11C]DPV 3-fold, resulting in a 7.5-fold reduced amount of excretion into the bile and the delayed elimination of [11C]DPV from the blood circulation. The hepatic uptake clearance (CLuptake, liver) and canalicular efflux clearance (CLint, bile) of [11C]DPV (544 ± 204 and 10.2 ± 3.5 µl/min per gram liver, respectively) in humans were lower than the previously reported corresponding parameters in rats (1800 and 298 µl/min per gram liver, respectively) (Shingaki et al., 2013). Furthermore, rifampicin treatment significantly reduced CLuptake, liver and CLint, bile by 58% and 44%, respectively. These results suggest that PET imaging with [11C]DPV is an effective tool for quantitatively characterizing the OATP1Bs and MRP2 functions in the human hepatobiliary transport system.


Adaptive Multimodal Fusion With Attention Guided Deep Supervision Net for Grading Hepatocellular Carcinoma.
Multimodal medical imaging plays a crucial role in the diagnosis and characterization of lesions. However, challenges remain in lesion characterization based on multimodal feature fusion. First, current fusion methods have not thoroughly studied the relative importance of characterization modals. In addition, multimodal feature fusion cannot provide the contribution of different modal information to inform critical decision-making. In this study, we propose an adaptive multimodal fusion method with an attention-guided deep supervision net for grading hepatocellular carcinoma (HCC). Specifically, our proposed framework comprises two modules: attention-based adaptive feature fusion and attention-guided deep supervision net. The former uses the attention mechanism at the feature fusion level to generate weights for adaptive feature concatenation and balances the importance of features among various modals. The latter uses the weight generated by the attention mechanism as the weight coefficient of each loss to balance the contribution of the corresponding modal to the total loss function. The experimental results of grading clinical HCC with contrast-enhanced MR demonstrated the effectiveness of the proposed method. A significant performance improvement was achieved compared with existing fusion methods. In addition, the weight coefficient of attention in multimodal fusion has demonstrated great significance in clinical interpretation.


4-Phenylbutan-2-one semicarbazone.
The title compound, C(11)H(15)N(3)O, crystallizes with two molecules in the asymmetric unit, which are held together by an extended network of hydrogen bonds. It is remarkable that only five of the six theoretically possible hydrogen bonds are formed.


Spontaneous uterine rupture at non-cesarean section scar site with placenta percreta in the second trimester: a case report.
Uterine rupture was a common occurrence at previously cesarean-sectioned scar Early sign ofuterine rupture was a severe fetal bradycardia. A 30-year-old, 3 gravida, 1 para woman was presented with an acute abdominal pain and hypovolemic shock. Her gestational age was estimated at 18 weeks by emergency pelvic ultrasound. She had a lower segment scar from a previous caesarean section. Initially, alive intrauterinepregnancy with massive hemoperitoneum was a provisional diagnosis. During exploratory laparotomy, a ruptured of the right uterine fundus was found with placenta percreta. Hysterectomy was performed. Fetal weight was 450 grams, APGAR score 0, 0 and the fetus could not survive. The patient was discharged on the 4th day after surgery in healthy condition. Uterine rupture is a catastrophic kituation. Severefetal bradycardia might be an early sign. This case demonstrates the importance ofclinical judgment based on clinical acumen.


Biosynthesis of phosphatidyl choline during prenatal development of the rat lung.
The biosynthesis of phosphatidyl choline in rat lung during prenatal development is of interest in connection with the mechanisms of functional development of the lung, particularly in relation to the production of lung surfactant and the control of phospholipid synthesis. The process was studied by determination of the ability of fetal and adult lung slices to incorporate choline-methyl-(14)C and methionine-methyl-(14)C into phosphatidyl choline. The incorporation of radioactivity from methionine-methyl-(14)C was low in both adult and fetal lung. There was no apparent change in the incorporation during development. The incorporation of choline-methyl-(14)C into phosphatidyl choline after 60 min of incubation was low for fetal lung at 19 days gestation and increased to adult levels by 22 days gestation. The incorporation of choline-methyl-(14)C into phosphoryl choline was high at 19 days gestation and decreased as development progressed. However, the specific activities of the phosphoryl choline were similar in fetal and adult lung, which suggests that the increase in incorporation of choline-methyl-(14)C into phosphatidyl choline with development results from an increased activity of reactions in the biosynthetic pathway between phosporyl choline and phosphatidyl choline.


Accelerated isotropic sub-millimeter whole-heart coronary MRI: compressed sensing versus parallel imaging.
To enable accelerated isotropic sub-millimeter whole-heart coronary MRI within a 6-min acquisition and to compare this with a current state-of-the-art accelerated imaging technique at acceleration rates beyond what is used clinically. Coronary MRI still faces major challenges, including lengthy acquisition time, low signal-to-noise-ratio (SNR), and suboptimal spatial resolution. Higher spatial resolution in the sub-millimeter range is desirable, but this results in increased acquisition time and lower SNR, hindering its clinical implementation. In this study, we sought to use an advanced B1-weighted compressed sensing technique for highly accelerated sub-millimeter whole-heart coronary MRI, and to compare the results to parallel imaging, the current-state-of-the-art, where both techniques were used at acceleration rates beyond what is used clinically. Two whole-heart coronary MRI datasets were acquired in seven healthy adult subjects (30.3 ± 12.1 years; 3 men), using prospective 6-fold acceleration, with random undersampling for the proposed compressed sensing technique and with uniform undersampling for sensitivity encoding reconstruction. Reconstructed images were qualitatively compared in terms of image scores and perceived SNR on a four-point scale (1 = poor, 4 = excellent) by an experienced blinded reader. The proposed technique resulted in images with clear visualization of all coronary branches. Overall image quality and perceived SNR of the compressed sensing images were significantly higher than those of parallel imaging (P = 0.03 for both), which suffered from noise amplification artifacts due to the reduced SNR. The proposed compressed sensing-based reconstruction and acquisition technique for sub-millimeter whole-heart coronary MRI provides 6-fold acceleration, where it outperforms parallel imaging with uniform undersampling.


A foodborne outbreak linked to Bacillus cereus at two middle schools in a rural area of Chongqing, China, 2021.
Bacillus cereus (B. cereus) is a common cause of foodborne illness. An outbreak of acute gastrointestinal illness occurred at two middle schools in a rural region of Chongqing, China, in 2021. This study aimed to elucidate the outbreak's characteristics, identify risk factors, and determine the source of contamination. A retrospective cohort study and an environmental investigation were conducted. Vomit samples, anal swabs, and food samples were collected and tested by RT-PCR for 18 species of bacteria and viruses, including B. cereus. Positive samples of B. cereus underwent biochemical experiments and bacterial quantification. A total of 198 cases were reported in this outbreak, with an attack rate of 24.63%. The main symptoms were vomiting (100%), bellyache (83.33%), and dizziness (62.63%). The retrospective cohort study showed a significant association between the outbreak and rice noodles provided by a nearby food manufacturer (RR = 39.63, p < 0.001). B. cereus was detected in 20 vomit samples, three anal swabs, and seven rice noodles samples, with a count exceeding 103 CFU/g. These findings strongly suggested that the outbreak was linked to B. cereus-contaminated rice noodles. Enhancing food safety surveillance and promoting health measures among schools and food manufacturers in rural areas is crucial to prevent similar incidents in the future in Chongqing, China.


Interleukin-1beta attenuates beta-very low-density lipoprotein uptake and its receptor expression in vascular smooth muscle cells.
The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor gene family with distinct tissue distribution and function. VLDL receptors are also expressed in vascular smooth muscle cells (VSMCs) and have been shown to be upregulated in atherosclerotic lesions. In the present study, we examined the effects of interleukin-1beta (IL-1beta) on the uptake of betaVLDL and its receptor expression in rat VSMCs. IL-1beta downregulated expression of the VLDL receptor in a time and dose-dependent manner as shown by Western blotting, Northern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Treatment with IL-1beta significantly reduced the uptake of beta-VLDL but not LDL in VSMCs. Use of specific pharmacologic inhibitors indicated that the tyrosine kinase inhibitors, herbimycin A and geldanamycin, completely reversed IL-1beta-induced downregulation of the VLDL receptor expression. Another tyrosine kinase inhibitor, genistein, the protein kinase C inhibitors, GF109203X and H7, the mitogen-activated protein (MAP) kinase inhibitors (MEK inhibitor PD098059 for [MEK] and SB203580 for p38-MAP kinase), and the protein kinase A inhibitor, KT5270 all had no effect on receptor expression. In addition, the c-Src specific inhibitor PP2 or adenoviral-mediated gene transfer of kinase inactive (KI)-c-Src failed to reverse IL-1beta-induced downregulation of VLDL receptor expression. These results indicate that IL-1beta attenuates uptake of VLDL through downregulation of its receptor in VSMCs, and that this downregulation is mediated through a benzoquinone ansamycin-dependent but c-Src-independent pathway.