Structure and function of embryonic rat retinal sheet transplants.
To evaluate retinal sheet transplants in S334ter-line-3 retinal degenerate rats by comparing visual responses recorded electrophysiologically with morphology based on light and electron microscopy. S334ter-line-3 retinal degenerate rats (n = 7) received retinal sheet transplants between postnatal days 28 and 31. The donor tissue was derived from transgenic embryonic day 19 (E19) rat retinae expressing human placental alkaline phosphatase (hPAP). Fresh retinal sheets were gently transplanted into the subretinal space of the left eye with the help of a custom-made implantation tool. Selected rats (n = 5) were subjected to electrophysiologic evaluation of visual responses from the superior colliculus about 84-121 days after surgery. Transplanted eyes were processed for light microscopy (LM) and electron microscopy (EM) evaluations. All the transplanted rats that were evaluated for visual responses in the brain showed responses to very low light stimulation (-3.42 to -2.8 log cd/m(2)) of the eye in a small area of the superior colliculus corresponding with the placement of the transplant in the host retina. Histologic evaluation showed that most of the transplants contained well-laminated areas with correct polarity in the subretinal space. Inside the transplant areas, rosettes of photoreceptors with inner and outer segments were found. In the laminated areas, the outer segments of photoreceptors were facing the host retinal pigment epithelium (RPE). Immunohistochemical evaluation of hPAP donor cells revealed areas with specific staining of the transplants in the subretinal space. Electron microscopic evaluation showed a glial demarcation membrane between the host and the transplant, however, processes originating from the transplant were observed inside the host retina. Sheets of E19 rat retina transplanted into the subretinal space of S334ter-line-3 rats survived without immune rejection and continued to show visual function when tested after 3 months. Well-developed photoreceptors and many synapse types were seen within the transplants. hPAP staining showed a certain degree of integration between the host retina and the transplant suggesting that transplanted photoreceptors contributed to the restored light sensitivity.


The immunoregulatory granulocyte factor (GF). III. Characteristics of target cells for GF.
Granulocyte factor (GF) is a substance secreted selectively from the specific granules of granulocytes in the first minutes of adherence or phagocytosis. GF possesses many immunoregulatory functions. We applied flow cytometric analysis to evaluate the target cells responsible for GF action. Resting lymphocytes did not display binding sites for GF, but 93 +/- 4.6% of the neutrophils isolated from peripheral blood bound GF (mean fluorescence = 122 +/- 11). GF was bound by 26 +/- 7.6% of the lymphocytes from nonstimulated and 42.6 +/- 12% of the lymphocytes from PHA-stimulated cultures, and the mean fluorescence intensity was 14.5 +/- 1 and 54 +/- 10.6, respectively. PHA-stimulated CD8+ cells presented higher expression of binding sites for GF than CD4+ cells. Binding sites for GF were found on 66 +/- 5.1% of activated cells expressing the receptor molecule to IL-2 (CD25) and 50.3 +/- 7.4% of cultured lymphocytes expressing the early activation marker CD69. These values were significantly higher in comparison to the percentage of CD25- and CD69- cells that bound FITC-labeled GF (10.3 +/- 3.3% and 11.3 +/- 3.5%, respectively). The binding was specific, and preincubation of the cells with GF almost completely abolished FITC-labeled GF binding. It has also been shown that GF binds to lymphocytes via molecules other than CD16. High-performance liquid chromatography (HPLC) with fractionated GF showed three separate fractions and two of them had GF-like activity, as demonstrated in the mixed lymphocyte reaction (MLR).


Formation of fibril structures in polymerizable, rod-coil-oligomer-modified epoxy networks.
This paper describes the in situ preparation of fibrils in epoxy networks in which the fibril-like structures are cured polymerizable rod-coil oligomers. The epoxy-terminated alpha,omega-modified PEO oligomers, which are ABA rod-coil-rod oligomers with a poly(ethylene oxide) coil unit and two aromatic azomethine liquid-crystalline rod units, were synthesized and then further blended with an epoxy precursor. Uniform nanoscale columnar structures were observed in the neat rod-coil oligomers as well as in the crosslinked liquid-crystalline state. During the curing of the blends, the supramolecular nanoscale columnar structures of the rod-coil oligomers are transformed into polymeric fibrils where the epoxy functional end groups have co-reacted with epoxy precursors to form a crosslinked network.


Existence of short-time approximations of any polynomial order for the computation of density matrices by path integral methods.
In this paper I provide significant mathematical evidence in support of the existence of direct short-time approximations of any polynomial order for the computation of density matrices of physical systems described by arbitrarily smooth and bounded from below potentials. While for Theorem 2, which is "experimental," I only provide a "physicist's" proof, I believe the present development is mathematically sound. As a verification, I explicitly construct two short-time approximations to the density matrix having convergence orders 3 and 4, respectively. Furthermore, in Appendix B, I derive the convergence constant for the trapezoidal Trotter path integral technique. The convergence orders and constants are then verified by numerical simulations. While the two short-time approximations constructed are of sure interest to physicists and chemists involved in Monte Carlo path integral simulations, the present paper is also aimed at the mathematical community, who might find the results interesting and worth exploring. I conclude the paper by discussing the implications of the present findings with respect to the solvability of the dynamical sign problem appearing in real-time Feynman path integral simulations.


MEDIAL TEMPORAL LOBE CONTRIBUTIONS TO FUTURE THINKING: EVIDENCE FROM NEUROIMAGING AND AMNESIA.
Following early amnesic case reports, there is now considerable evidence suggesting a link between remembering the past and envisioning the future. This link is evident in the overlap in neural substrates as well as cognitive processes involved in both kinds of tasks. While constructing a future narrative requires multiple processes, neuroimaging and lesion data converge on a critical role for the medial temporal lobes (MTL) in retrieving and recombining details from memory in the service of novel simulations. Deficient detail retrieval and recombination may lead to impairments not only in episodic, but also in semantic prospection. MTL contributions to scene construction and mental time travel may further compound impairments in amnesia on tasks that pose additional demands on these processes, but are unlikely to form the core deficit underlying amnesics' cross-domain future thinking impairment. Future studies exploring the role of episodic memory in other forms of self-projection or future-oriented behaviour may elucidate further the adaptive role of memory.


[Neuronal Correlation Between Acupoint BL 23 and the Adrenal Gland in Rats].
To explore the neuroanatomical basis of acupoint-visceral correlation by studying the distribution of the neurons associated with acupoint "Shenshu" (BL 23) area and adrenal gland in rats. AF 488-CTB and AF 594-CTB were injected into the left side of BL 23 area and adrenal gland in the same rat respectively. Three days after injection, the dorsal root ganglions (DRG), sympathetic chain, and spinal cord were dissected out from the perfused rats. The neuronal labeling with AF 488/594-CTB was directly observed on the sections under a fluorescent microscope or a laser scanning confocal microscope. All neural labeling was observed in the injection side. The sensory neurons associated with both acupoint BL 23 and adrenal gland distributed from thoracic (T) 10 to lumbar (L) 2 DRG with high concentration in T 12-T 13 and T 11-T 12, respectively, in which some of them were simultaneously labeled with both AF 488/594-CTB and located in T 12-L 1 DRG. For the sympathetic innervation, the postganglionic neurons correlated with BL 23 and adrenal gland were labeled with AF 488/594-CTB separately in the sympathetic chain at the lumbar segments, while the labeled preganglionic neurons were only observed at the lateral horn of T 11-T 13 spinal segments in the cases of adrenal gland. In addition, the labeled motor neurons were mainly detected in the spinal ventral horn at cervical (C) 7-C 8 and T 11-L 1 segments. These results indicate that there are segmental correlation between BL 23 and adrenal gland on the sensory and sympathetic innervations, and this correlation might be a neural pathway for modulating the function role of adrenal gland through BL 23 needling.


Local time horizons in Pavlovian learning.
Responding to a conditioned stimulus (CS) is impaired if the CS is trained in the presence of excitatory local context cues. Four lick suppression experiments with rats explored whether this local context effect arises from the influence of excitatory cues that precede or that follow a reinforced target CS. Pretrained nontarget stimuli served as local context cues that occurred (a) immediately before and after the target CS trial, (b) immediately before or after the target CS trial, or (c) only before or after the target CS trial with varying intervals between the nontarget stimulus and target CS. Results indicated similar control over responding to the target CS by the preceding and following nontarget cues. This outcome implies a symmetrical window of memory integration (local time horizon) for a Pavlovian CS. Possible mechanisms underlying the detrimental effect of embedding a CS in an excitatory local context are discussed.


Chiral clusters in a supersonic beam: R2PI-TOF spectroscopy of diastereomeric carboxylic esters/(R)-(+)-1-phenyl-1-propanol complexes.
Wavelength and mass resolved resonance-enhanced two photon ionization (R2PI) excitation spectra of (R)-(+)-1-phenyl-1-propanol (P(R)) and its complexes with some chiral esters, i.e. methyl lactates (L(R) and L(S)), methyl 3-hydroxybutyrates (H(R) and H(S)), and methyl 2-chloropropionates (C(R) and C(S)), have been recorded after a supersonic molecular beam expansion and interpreted in the light of DFT calculations. The spectral features of the selected complexes were found to depend on the nature of hydrogen-bond interactions within the diasteromeric complexes, whose intensity in turn depends upon the structure and the configuration of the estereal moiety. The study further confirms resonant two-photon ionization spectroscopy, coupled with time-of-flight mass resolution (R2PI-TOF), as an excellent tool for gathering valuable information on the interactive forces in molecular clusters and for the enantiodiscrimination of chiral molecules in the gas phase.


Oral adenoid/acantholytic squamous cell carcinoma: a report of two cases with review of literature.
Adenoid squamous cell carcinoma (ASCC) is an uncommon but well recognized variant of squamous cell carcinoma. It has been reported to originate in the sun exposed skin of the head and neck region. Although rare, there are cases in records which have reported within the oral cavity and nasopharynx. Histologically the lesion shows areas of conventional squamous cell carcinoma along with atypical epithelial cells forming an adenoid pattern. There are insufficient reported cases to establish likely behaviour. Here we report two additional cases of adenoid squamous cell carcinoma, one developing in the floor of mouth and another in the maxillary sinus both were reported in March 2010 in Mangalore, India.


Outcomes of dogs with grade 3 mast cell tumors: 43 cases (1997-2007).
This study reports the outcomes of dogs with grade 3 mast cell tumors (MCTs). Clinical and histopathological data were available for 43 dogs. Median progression-free survival (PFS) and overall survival (OS) were 133 and 257 days, respectively. Tumor size, lymph node (LN) status, and mitotic index (MI) significantly influenced PFS in univariate analysis. Tumor size and LN status remained significant in the multivariate analysis. Lymph node status, local tumor control, LN treatment, and MI significantly influenced OS in univariate analysis but only LN status remained significant in multivariate analysis. These results confirm that locoregional control improves outcomes in patients with grade 3 MCTs.


Effect of pigment on photomediated production of thymine dimers in cultured melanoma cells.
It was the aim of these studies to determine whether the presence of intracellular melanin quantitatively alters the rate of production of thymine dimers in DNA of irradiated cells in culture. Pigmented and nonpigmented Cloudman mouse melanoma cells were selected assuming that the two cell lines differ primarily in their content of melanin pigment. Cells were cultivated in tritiated thymine in order to label their DNA and were then exposed to ultraviolet (UV) irradiation (260 nm, 500-2000 ergs/mm2). Neither cell line survived these doses of irradiation. DNA was extracted immediately following irradiation and was subjected to acid hydrolysis. The presence of thymine dimers was determined by two-dimensional paper chromatography. The percent of labeled thymine recovered as thymine dimer was calculated and was found to be a linear function of UV dose for both cell lines. The rate of formation of dimers in the nonpigmented cells was nearly twice that in the pigmented cells. These data demonstrate the photoprotective property of intracellular melanin in shielding isolated cells from one type of photomediated injury to DNA.


Predictors of Ketogenic Diet Efficacy in Children Based on the Electroencephalogram (EEG).
It is unclear whether electrographic features are predictive of ketogenic diet efficacy and how evolution of electroencephalogram (EEG) findings correlates with clinical improvement. We aimed to identify predictors for clinical seizure reduction on the diet as it correlates with serial EEGs. We reviewed 89 patients on the diet at Children's Medical Center from 2005 to 2012. We developed scoring criteria to analyze EEG characteristics (2 scales: 0-3 for encephalopathy; 0-6 for interictal discharges). Those with the lowest encephalopathy scores on last EEG strongly correlated with seizure reduction in patients with >95% seizure reduction (P = .002). A change in encephalopathy scores in those with moderate-severe encephalopathy on first EEG also correlated with >95% reduction in seizures (P = .009). This supports the theory that serial EEGs can be helpful in predicting positive therapeutic outcomes on the diet. Of 43 patients with both initial and follow-up EEGs, 27 had a decrease in interictal epileptic discharge frequency, though this was not significant (P = .434).


Alcohol intoxication and post-burn complications.
Results from the studies discussed in this article suggest that alcohol (EtOH) intoxication is a major public health problem. While the effects of injury and EtOH intoxication independent of each other have been studied in detail, only few studies have evaluated the effect of a combined insult of EtOH intoxication and burn injury on host defense. An analysis of the studies conducted in the clinical setting suggests that intoxicated patients require frequent intubations, experience delayed wound healing and longer hospital stay. Furthermore, there is a greater risk of mortality in these patients compared to those who sustained injuries in the absence of EtOH intoxication. On the other hand, there are a few studies that do not support this notion. The results obtained in experimental models clearly suggest that acute EtOH intoxication before burn injury impairs host defense and increases susceptibility to infection. Additionally, experimental data from our laboratory also indicate that EtOH intoxication before burn injury suppresses intestinal immune defense, impairs gut barrier functions and increases bacterial growth. This results in increased bacterial translocation in EtOH and burn injury. In addition, a decrease in cardiac function is also reported following a combined insult of EtOH intoxication and burn injury. Altogether, these findings suggest that EtOH intoxication before burn injury diminishes host resistance resulting in increased susceptibility to infection. Moreover, the findings of a higher incidence of infectious complications in burn and trauma patients who sustained injury in the presence of EtOH compared to those in its absence suggest that EtOH intoxication at the time of injury is a risk factor. Therefore blood EtOH should be monitored in burn/trauma patients at the time of admission in the emergency room.


Biosynthesis of putrescine in the prostate gland of the rat.
In the rat ventral prostate gland the biosynthesis of putrescine, a precursor of spermidine and spermine, is shown to occur by the direct decarboxylation of l-ornithine. Some properties of a soluble pyridoxal phosphate-dependent l-ornithine decarboxylase are described. The findings are discussed in relation to other enzymic reactions involved in the biosynthesis of polyamines by the prostate gland.


Molecular epidemiology of peste des petits ruminants virus in Nigeria: An update.
Peste des petits ruminants (PPR) is a highly contagious viral disease that mainly affects goats and sheep in Asia, Africa and the Middle East. The PPR virus (PPRV) can be classified into four genetically distinct lineages (I, II, III and IV). All have been historically present in Africa, except the Asian lineage IV that has been spreading across the globe and across Africa in recent decades. Previous studies have identified the presence of lineage IV in Nigeria since 2010. In the present study, samples were taken from 429 small ruminants with PPR symptoms across Nigeria in 2017-2020 to provide an update on the distribution and genetic diversity of PPRV in the country. Sequences from a portion of the PPRV nucleoprotein (N) gene were obtained from 91 samples, 90 belonging to lineage IV and one to lineage II. Phylogenetic analysis identified at least four lineage IV sub-clusters in Nigeria, grouping samples across multiple regions. Our results suggest extensive endemic circulation of a wide range of PPRV strains across Nigeria and across borders with neighbouring countries, underlining the difficulty involved in controlling the disease in the region.


Matrix metalloproteinase- 9 polymorphisms in the diagnosis of prostate cancer. A preliminary experience.
Polymorphisms Q279R, P574R and -1562 C/T of matrix metalloproteinase-9 (MMP-9) gene have been linked with the risk of cancer and with tumoral aggressiveness in various types of cancer. So far there are no studies in the literature analysing the link between polymorphisms Q279R, P574R and -1562 C/T of MMP-9 and prostate cancer. To establish the presence of the MMP-9's gene polymorphisms (Q279R, P574R and -1562 C/T)in relation to results of prostate biopsy, PSA values and Gleason score. Hospital cohort of 100 patients with suspected prostate cancer, subjected to prostate biopsy, in whom the MMP-9 polymorphisms (Q279R, P574R and -1562 C/T) were analysed using the PCR-RLFP technique. No statistically significant differences were found in the presence of the Q279R, P574R and -1562 C/T polymorphisms in terms of prostate biopsy results (p = 0.264, p = 0.406, p = 0.860, respectively), or Gleason score (p = 0.373, p = 0.367, p = 0.476). Comparing the genotypes of the Q279R, P574R and -1562 C/T polymorphisms resulting from prostate biopsy, using subgroups according to PSA values, no statistically significant differences were found either (p = 0.332 y p = 0.393, respectively ). However, statistically significant differences were found when comparing the genotypes of the -1562 C/T polymorphism of the MMP-9 in patients showing positive biopsy for malignant tumour in comparison to a negative biopsy for a malignant tumour in the subgroup of patients with PSA 10 ng/ml (p=0.049). The joint analysis of the three MMP-9 polymorphisms, using logistical regression study did not reveal any statistically significant differences as far as the risk of developing prostate cancer is concerned based on the presence of the Q279R, P574R and -1562 C/T polymorphisms. The Q279R, P574R and -1562 C/T polymorphisms are not linked with the aggressiveness in prostate cancer, neither they are linked to the risk of suffering prostate cancer.


The value of the sagittal-oblique MRI technique for injuries of the anterior cruciate ligament in the knee.
Complete rupture of the anterior cruciate ligament (ACL) does not represent a diagnostic problem for the standard magnetic resonance (MR) protocol of the knee. Lower accuracy of the standard MR protocol for partial rupture of the ACL can be improved by using additional, dedicated MR techniques. The study goal was to draw a comparison between sagittal-oblique MR technique of ACL imaging versus flexion MR technique of ACL imaging and, versus ACL imaging obtained with standard MR protocol of the knee. In this prospective study we included 149 patients who were referred to magnetic resonance imaging (MRI) examination due to knee soft tissues trauma during 12 months period. MRI signs of ACL trauma, especially detection of partial tears, number of slices per technique showing the whole ACL, duration of applied additional protocols, and reproducibility of examination were analysed. Accuracy of standard MRI protocol of the knee comparing to both additional techniques is identical in detection of a complete ACL rupture. Presentations of the partial ruptures of ACL using flexion technique and sagittal-oblique technique were more sensitive (p<0.001) than presentation using standard MR protocol. There was no statistically significant difference between MRI detection of the ruptured ACL between additional techniques (p> 0.65). Sagittal-oblique technique provides a higher number of MRI slices showing the whole course of the ACL and requires a shorter scan time compared to flexion technique (p<0.001). Both additional techniques (flexion and sagittal-oblique) are just as precise as the standard MR protocol for the evaluation of a complete rupture of the ACL, so they should be used in cases of suspicion of partial rupture of the ACL. Our study showed sagittal-oblique technique was superior, because it did not depend on patient's ability to exactly repeat the same external rotation if standard MR protocol was used or to repeat exactly the same flexion in flexion MR technique in further MR examinations. Sagittal-oblique technique does not require the patient's knee to be repositioned, which makes this technique faster. We propose this technique in addition to the standard MR protocol for detection of partial ACL tears.


Inhibitory effect of interferon-gamma on the response of human thyrocytes to thyrotropin (TSH) stimulation: relationship between the response to TSH and the expression of DR antigen.
Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.


Creative Destruction and Subjective Well-Being.
In this paper we analyze the relationship between turnover-driven growth and subjective wellbeing. Our model of innovation-led growth and unemployment predicts that: (i) the effect of creative destruction on expected individual welfare should be unambiguously positive if we control for unemployment, less so if we do not; (ii) job creation has a positive and job destruction has a negative impact on wellbeing; (iii) job destruction has a less negative impact in US Metropolitan Statistical Areas (MSA) within states with more generous unemployment insurance policies; (iv) job creation has a more positive effect on individuals that are more forward-looking. The empirical analysis using cross-sectional MSA-level and individual-level data provide empirical support to these predictions.


Safety and efficacy of current alternatives in the topical treatment of cutaneous leishmaniasis: a systematic review.
Studies of topical treatments for leishmaniasis were systematically reviewed, to evaluate the therapeutic efficacy, safety and any adverse effects of these treatments. The papers identified in the databases PubMed and Web of Knowledge involved eight studies with a total of 1744 patients. The majority of trials was from Iran (4/8), covered a period of 8 years (2003-2011), and included patients 4-85 years of age. The most frequent Leishmania species in the studies were L. tropica (4/8) and L. major (2/8). The treatments administered were thermotherapy, paromomycin and combinations, CO2 laser, 5-aminolevulinic acid hydrochloride (10%) plus visible red light (633 nm) and cryotherapy. Six articles reported cure rates over 80·0%. Six studies reported on failure rates, three of them reporting rates lower than 10%. Four studies did not report relapses or recurrences, while the other studies reported low rates (1·8-6·3%). The most common adverse effects of the topical treatments were redness/erythema, pain, pruritus burning, oedema, vesicles and hyper- or hypopigmentation. The results provide strong evidence that the treatments topical evaluated showed high cure rates, safety and effectiveness, with low side-effects, relapse and recurrence rates, except for cryotherapy, which showed a moderate cure rate.


Reduction factors for wooden houses due to external γ-radiation based on in situ measurements after the Fukushima nuclear accident.
For estimation of residents' exposure dose after a nuclear accident, the reduction factor, which is the ratio of the indoor dose to the outdoor dose is essential, as most individuals spend a large portion of their time indoors. After the Fukushima nuclear accident, we evaluated the median reduction factor with an interquartile range of 0.43 (0.34-0.53) based on 522 survey results for 69 detached wooden houses in two evacuation zones, Iitate village and Odaka district. The results indicated no statistically significant difference in the median reduction factor to the representative value of 0.4 given in the International Atomic Energy Agency (IAEA)-TECDOC-225 and 1162. However, with regard to the representative range of the reduction factor, we recommend the wider range of 0.2 to 0.7 or at least 0.2 to 0.6, which covered 87.7% and 80.7% of the data, respectively, rather than 0.2 to 0.5 given in the IAEA document, which covered only 66.5% of the data. We found that the location of the room within the house and area topography, and the use of cement roof tiles had the greatest influence on the reduction factor.


The presence of chorionic gonadotrophin beta subunit in normal cyclic human endometrium.
The aim of the present study was to determine whether human endometrial cells are able to secrete beta-chorionic gonadotrophin (betaCG). Immunohistochemical studies and in-situ hybridization were performed in order to provide evidence for the occurrence of betaCG in the normal endometrium in 15 patients in the proliferative phase, two patients in the periovulatory phase and 13 patients in the secretory phase. Neither immunohistochemical nor hybridization reactions could be recognized during the proliferative phase. In contrast, both protein and betaCG mRNA were observed in the glandular cells of the endometrium during the secretory phase. The results were supported by Western blotting of secretory phase endometrium extracts and the assessment of the functional secretory capacity of primary endometrium cultures. In comparison with cultured and separated cell fractions, tissue extracts showed a higher betaCG, indicating a regulatory interaction. In conclusion, betaCG can be demonstrated in normal human cyclic endometrium, suggesting a paracrine role in endometrial physiology.


Enantioselective synthesis of gamma-hydroxyenones by chiral base-catalyzed Kornblum DeLaMare rearrangement.
A cinchona-alkaloid catalyzed asymmetric Kornblum DeLaMare rearrangement has been developed. Thus, enantioenriched 4-hydroxyenones are prepared from dienes by a two-step sequence involving photochemical dioxygenation and chiral base-catalyzed desymmetrization of the resulting endoperoxides.


[The analysis of the commission forensic medical expertises concerning charges against healthcare providers].
This article as designed to present the results of the many-year analysis of the results and procedures of commission medical expertises concerning charges against healthcare providers as exemplified by the activities in these fields carried out by the Saint-Petersburg Bureau of Forensic Medical Expertise. The analysis has demonstrated the well apparent tendency toward the growth in the number of expertises necessitated by the constantly increasing frequency of private claims and complaints in connection with the inadequacy and/or poor quality of medical assistance provided for the population. This growth may be attributable either to the enhanced activities of the judicial and investigation governmental bodies (including the increased frequency and periodicity of the planned inspections of the cases of lethal outcomes) or to the more active behavior of the patients themselves exhibiting a greater than during the preceding period concern about their health status (or both).


The endothelial cytoskeleton as a target of electroporation-based therapies.
Electroporation-based therapies, such as electrochemotherapy and electrogene therapy, result in the disruption of blood vessel networks in vivo and cause changes in blood flow and vascular permeability. The effects of electroporation on the cytoskeleton of cultured primary endothelial cells and on endothelial monolayer permeability were investigated to elucidate possible mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were electroporated in situ and then immunofluorescence staining for filamentous actin, beta-tubulin, vimentin, and VE-cadherin as well as Western blotting analysis of levels of phosphorylated myosin light chain and cytoskeletal proteins were performed. Endothelial permeability was determined by monitoring the passage of FITC-coupled dextran through endothelial monolayers. Exposure of endothelial cells to electric pulses resulted in a profound disruption of microfilament and microtubule cytoskeletal networks, loss of contractility, and loss of vascular endothelial cadherin from cell-to-cell junctions immediately after electroporation. These effects were voltage dependent and reversible because cytoskeletal structures recovered within 60 min of electroporation with up to 40 V, without any significant loss of cell viability. The cytoskeletal effects of electroporation were paralleled by a rapid increase in endothelial monolayer permeability. These results suggest that the remodeling of the endothelial cytoskeleton and changes in endothelial barrier function could contribute to the vascular disrupting actions of electroporation-based therapies and provide an insight into putative mechanisms responsible for the observed increase in permeability and cessation of blood flow in vivo.


Timing of seroconversion and acquisition of positive polymerase chain reaction assay results in calves experimentally infected with bovine leukemia virus.
To determine the interval to provirus and serum antibody detection (via PCR assay and ELISA, respectively) in calves after experimental inoculation with bovine leukemia virus (BLV). 8 colostrum-deprived, BLV-negative Holstein bull calves (> or = 6 weeks old). Via IM injection, each calf received a fresh whole-blood inoculum (day 0) calculated to contain 2 x 10(6) lymphocytes. Blood samples for the ELISA and PCR assay were collected from calves immediately prior to inoculation and weekly thereafter for 7 weeks. Mean and median number of weeks to PCR-detected conversion of BLV status and seroconversion were calculated. Point sensitivity and cumulative sensitivity of the 2 assays were calculated at each sample collection. At each sampling time, the proportion of calves identified as infected by the cumulative weekly ELISA and PCR assay results was compared by use of a Fisher exact test. In 5 calves, conversion of BLV status was detected via PCR assay before seroconversion was identified. However, seroconversion preceded PCR-detected conversion in 2 calves. In 1 calf, both assays yielded positive results at the same test date. These differences were not significant. In experimentally inoculated BLV-negative calves, conversion of BLV status was detected via PCR assay more quickly than via ELISA; this difference was not significant and probably not clinically important. The PCR assay may be useful as a confirmatory test in animals of exceptional value; tests based on viral identification may become critically important if vaccines against BLV infection are developed and marketed.


The politics of deteriorating health: the case of Palestine.
This article reviews the deteriorating health situation of the Palestinian population during the post-Oslo period of the Palestinian Authority and during the current Intifada. It seeks to record findings obtained through primary participants and documents and from personal observations in the field that situate Palestinian health conditions within their political framework. The ongoing crisis highlights longstanding problems in the Palestinian health infrastructure, which make it more vulnerable to Israeli policies, especially the movement restrictions and closures. Efforts by Palestinian professionals and the international health community to provide health services have been constantly thwarted. The Israeli authorities' disregard for Palestinian health care has escalated since 2000 and is directly responsible for a vast number of Palestinian deaths. Israel's indiscriminate obstructions to the coordinated functioning of a health care system in Palestine increase morbidity, degrade health, promote premature deaths, and damage the medical infrastructure. Moreover, the Israeli actions transgress international law and, ultimately, make peace in the region much less likely. This analysis provides further evidence of the social justice violations and the wide-ranging effects on health experienced daily by the Palestinian people as a direct result of the Israeli military occupation.


Functional genomics and gene expression profiling in sepsis: beyond class prediction.
Functional genomics involving genome-wide expression analyses is rapidly finding applications in clinical medicine. New technologies now permit the simultaneous analysis of mRNA levels for the entire human transcriptome from as few as 1000 cells. This approach is dramatically changing the way we define health and disease, allowing, for the first time, an unbiased view of the global changes in gene expression that are occurring. For the study of trauma biology and sepsis, this technology offers a powerful tool to develop molecular signatures for inflamed tissues and specific cell populations. At present, functional genomics is being used to classify the progress of disease and survival in response to traumatic and burn injury, sepsis and visceral ischemia, and reperfusion injury, as well as to describe patterns of gene expression in response to varying microbial pathogens. As the number of bioinformatics tools increases, functional genomics is beginning to reveal the underlying complexity of the biological response to a variety of inflammatory diseases and is providing new approaches for their exploration. Functional genomics is becoming a standard tool in inflammation research as a means to unravel the basic biological processes.


Camrelizumab plus Famitinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: Data from an Open-label, Multicenter Phase II Basket Study.
Blockade of immune checkpoint and angiogenesis is an effective treatment strategy for advanced or metastatic renal cell carcinoma (RCC). We report the results of camrelizumab plus famitinib in the RCC cohort of an open-label, multicenter, phase II basket study. Eligible patients were enrolled to receive camrelizumab (200 mg i.v. every 3 weeks) and famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per RECIST version 1.1. Totally, 38 patients were recruited, including 13 (34.2%) treatment-naïve and 25 (65.8%) previously treated patients. With a median duration from enrollment to data cutoff of 16.5 months (range, 6.1-20.4), 23 patients achieved a confirmed objective response, and ORR was 60.5% [95% confidence interval (CI), 43.4-76.0]. Responses in 18 (78.3%) responders were still ongoing, and Kaplan-Meier estimated median duration of response had not been reached yet (range, 1.0+-14.8+ months). Median progression-free survival (PFS) was 14.6 months (95% CI, 6.2-not reached). ORR was 84.6% (95% CI, 54.6-98.1) in treatment-naïve patients and 48.0% (95% CI, 27.8-68.7) in pretreated patients; median PFS had not been reached and was 13.4 months (95% CI, 4.1-not reached), respectively. Most common grade 3 or 4 treatment-related adverse events included proteinuria (18.4%), hypertension (18.4%), decreased neutrophil count (13.2%), palmar-plantar erythrodysesthesia syndrome (10.5%), and hypertriglyceridemia (10.5%). No treatment-related deaths occurred, and no new safety signals were observed. Camrelizumab plus famitinib showed potent and enduring antitumor activity in patients with advanced or metastatic RCC, both in treatment-naïve and previously treated population.


Prevention of psychological distress in persons with inflammatory bowel disease.
This paper presents an overview of IBD with a critical analysis of the causes and effects of psychological distress in persons with this illness. Based on this literature, risk factors for the development of psychological distress are delineated. It is recognition of these risk factors for the development and the early signs of psychological distress in this population that can enable nurses to prevent this unfortunate psychosocial consequence of this disease. Preventive interventions discussed include the following: treating comorbid psychiatric illness, enhancing problem-solving coping, facilitating mourning and grieving, reducing stress, enhancing the positive appraisal of uncertainty, increasing personal control, increasing social support, and educating patients, families, and others.


Effect of D-Glucarates on basic antibiotic-induced renal damage in rats.
Dehydrated rats regularly develop acute renal failure following single injection of aminoglycoside antibiotics combined with dextran or of antibiotics only. Oral administration of 2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone protected rats against renal failure induced by kanamycin-dextran. The protective effect was prevalent among D-glucarates, and also to other saccharic acid, hexauronic acids and hexaaldonic acids, although to a lesser degree, but not to a hexaaldose, sugar alcohols, substances inthe TCA cycle and other acidic compounds. D-Glucarates were effective against renal damage induced by peptide antibiotics as well as various aminoglycoside antibitocis. Dose-responses were observed in the protective effect of D-Glucarates. With a D-glucarate of a fixed size of dose, approximately the same degree of protection was obtained against renal damages induced by different basic antibiotics despite large disparities in administration doses of different antibiotics. D-Glucarates had the ability to prevent renal damage but not to cure it. Rats excreted acidic urine when they were spared from renal lesions by monosaccharides. The reduction effect of D-glucarates against nephrotoxicity of basic antibiotics was discussed.


Injection techniques for common arm disorders.
The most junior resident medical officer soon becomes proficient at lumbar puncture and pleural aspiration but placement of a needle in a synovial cavity is approached with less confidence. Although only a part of the management of soft tissue rheumatic conditions, a carefully given corticosteroid injection can be dramatically effective for severe pain localised to a bursa, tendon sheath or synovial space.


Localized salt-dependent aquagenic urticaria, a rare subtype of urticaria: a case report.
Aquagenic urticaria (AU) is a rare form of chronic inducible urticaria elicited by water at any temperature. We describe the case of a 25-year-old atopic woman who presented to our unit with a 4-year history of recurrent urticarial rashes, highly pruritic, confined to the neck and lower part of the face, occurring solely on contact with sea water. The lesions were reproduced by challenge tests with aqueous 3.5% NaCl and other hypertonic aqueous solutions but not with 20% glucose neither tap water. Our case supports the existence of a distinct salt-dependent subtype of aquagenic urticaria (SDAU), which seems to be triggered mostly by sea bathing, affects young women and has a characteristic localization on the inferior facial contours and neck. To the best of our knowledge, only eight cases of SDAU have been reported in the literature.


Inappropriate therapy for methicillin-resistant Staphylococcus aureus: resource utilization and cost implications.
Methicillin-resistant Staphylococcus aureus causes significant morbidity and mortality. Initially inappropriate antibiotic therapy for methicillin-resistant S. aureus increases the risk for mortality. The impact of initially inappropriate antibiotic therapy on hospital length of stay and costs remains unknown. We identified patients admitted with nonnosocomial methicillin-resistant S. aureus sterile-site infections during a 3 yr period and compared those given appropriate antibiotic therapy with those given initially inappropriate antibiotic therapy. Appropriate therapy was defined based on timely administration of an anti-infective to which the pathogen was in vitro susceptible. Hospital length of stay served as the primary end point whereas total hospital costs represented a secondary end point. We attempted to adjust for multiple potential confounders including demographics, comorbid illnesses, infection characteristics, and severity of illness. We conducted subgroup analyses in patients who survived their hospital stay and in those requiring admission to the intensive care unit. The cohort included 291 patients and 77% received initially inappropriate antibiotic therapy. Approximately one in five patients died during their hospitalization. The median length of stay among the appropriately treated population was 2 days shorter than those given initially inappropriate antibiotic therapy (7.1 vs. 9.3 days, p = .050). After adjusting for covariates in a Cox proportional hazards model, initially appropriate therapy remained associated with a reduced length of stay (hazard ratio: 0.69, 95% confidence interval: 0.51-0.92, p = .013). Median crude costs in those treated appropriately were $13,688 compared with $19,427 (p = .019). Restricting the analysis to either hospital survivors or to those needing intensive care did not alter our observations. Initially inappropriate antibiotic therapy for methicillin-resistant S. aureus prolongs length of stay and increases hospital costs. Efforts to lower rates of initially inappropriate antibiotic therapy for methicillin-resistant S. aureus sterile-site infections will likely improve outcomes for both patients and for healthcare institutions.


Enhancing photocurrent transient spectroscopy by electromagnetic modeling.
The shape and duration of photocurrent transients generated by a photoconductive switch depend on both the intrinsic response of the active material and the geometry of the transmission line structure. The present electromagnetic model decouples both shape forming contributions. In contrast to previously published work, it accounts for the particular operating mode of transient spectroscopy. The objective is to increase the time resolution by two approaches, by optimizing structural response and by deconvolving it from experimental data. The switch structure is represented by an effective transimpedance onto which the active material acts as current generator. As proof of concept, the response of a standard microstrip switch is modeled and deconvolved from experimental data acquired in GaAs, yielding a single exponential material response and hence supporting the validity of the approach. Beyond compensating for the response deterioration by the structure, switch architectures can be a priori optimized with respect to frequency response. As an example, it is shown that a microstrip gap that can be deposited on materials incompatible with standard lithography reduces pulse broadening by an order of magnitude if it is provided with transitions to coplanar access lines.


Integrating the Lactational Amenorrhea Method into a family planning program in Ecuador.
This paper reports the results of a 12-month implementation study documenting the process of integrating the Lactational Amenorrhea Method (LAM) into a multiple-method family planning service-delivery organization, the Céntro Médico de Orientación y Planificación Familiar (CEMOPLAF), in Ecuador. LAM was introduced as a family planning option in four CEMOPLAF clinics. LAM was accepted by 133 breastfeeding women during the program's first five months, representing about one-third of postpartum clients. Seventy-three percent of LAM acceptors were new to any family planning method. Follow-up interviews with a systematic sample of 67 LAM users revealed that the method was generally used correctly. Three pregnancies were reported, none by women who were following LAM as recommended. Service providers' knowledge of LAM resulted in earlier IUD insertions among breastfeeding women. Relationships with other maternal and child health organizations and programs were also established.


Adjuvanticity and arthritogenicity of silicone.
Potential adjuvanticity and arthritogenicity of silicone obtained from a mammary implant were investigated. Silicone, injected intraperitoneally in conjunction with heat-killed Mycobacterium tuberculosis and EL4 cells (mouse tumor cell, H-2b), failed to enhance the development of immune response directed toward EL4 cells in Lewis rats. Subplantar injection of silicone, alone or in combination with heat-killed M. tuberculosis, also failed to induce adjuvant arthritis in Lewis rats. These findings suggest that silicone has neither adjuvant activity nor arthritogenic property and is not an effective substitute for the mineral oil component of Freund's adjuvant.


Sex differences in glutamate AMPA receptor subunits mRNA with fast gating kinetics in the mouse cochlea.
Evidence shows that females have increased supra-threshold peripheral auditory processing compared to males. This is indicated by larger auditory brainstem responses (ABR) wave I amplitude, which measures afferent spiral ganglion neuron (SGN)-auditory nerve synchrony. However, the underlying molecular mechanisms of this sex difference are mostly unknown. We sought to elucidate sex differences in ABR wave I amplitude by examining molecular markers known to affect synaptic transmission kinetics. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) mediate fast excitatory transmission in mature SGN afferent synapses. Each AMPAR channel is a tetramer composed of GluA2, 3, and 4 subunits (Gria2, 3, and 4 genes), and those lacking GluA2 subunits have larger currents, are calcium-permeable, and have faster gating kinetics. Moreover, alternatively spliced flip and flop isoforms of each AMPAR subunit affect channel kinetics, having faster kinetics those AMPARs containing Gria3 and Gria4 flop isoforms. We hypothesized that SGNs of females have more fast-gating AMPAR subunit mRNA than males, which could contribute to more temporally precise synaptic transmission and increased SGN synchrony. Our data show that the index of Gria3 relative to Gria2 transcripts on SGN was higher in females than males (females: 48%; males: 43%), suggesting that females have more SGNs with higher Gria3 mRNA relative to Gria2. Analysis of the relative abundance of the flip and flop alternatively spliced isoforms showed that females have a 2-fold increase in fast-gating Gria3 flop mRNA, while males have more slow-gating (2.5-fold) of the flip. We propose that Gria3 may in part mediate greater SGN synchrony in females. Significance Statement: Females of multiple vertebrate species, including fish and mammals, have been reported to have enhanced sound-evoked synchrony of afferents in the auditory nerve. However, the underlying molecular mediators of this physiologic sex difference are unknown. Elucidating potential molecular mechanisms related to sex differences in auditory processing is important for maintaining healthy ears and developing potential treatments for hearing loss in both sexes. This study found that females have a 2-fold increase in Gria3 flop mRNA, a fast-gating AMPA-type glutamate receptor subunit. This difference may contribute to greater neural synchrony in the auditory nerve of female mice compared to males, and this sex difference may be conserved in all vertebrates.


Theoretical studies on molecular determinants for recognition at H3 histamine receptors.
The determinants for recognition at H3 histamine receptors are considered. Findings based on quantum-chemical calculations suggest that H3 histamine receptor is less hydrophilic than the H2. The form most likely to be recognized by the H3 receptor is an intramolecularly hydrogen-bonded form of alpha-methylhistamine. Receptor environment and hydration effects of active form of histamine analogs are of crucial importance.


Characterization of the adhesive mucilages secreted by live diatom cells using atomic force microscopy.
Atomic Force Microscopy (AFM) resolved the topography and mechanical properties of two distinct adhesive mucilages secreted by the marine, fouling diatom Craspedostauros australis. Tapping mode images of live cells revealed a soft and cohesive outer mucilage layer that encased most of the diatom's siliceous wall, and force curves revealed an adhesive force of 3.58 nN. High loading force, contact mode imaging resulted in cantilever 'cleaned' cell walls, which enabled the first direct observation of the active secretion of soft mucilage via pore openings. A second adhesive mucilage consisted of strands secreted at the raphe, a distinct slit in the silica wall involved in cell-substratum attachment and motility. Force measurements revealed a raphe adhesive strand(s) resistant to breaking forces up to 60 nN, and these strands could only be detached from the AFM cantilever probe using the manual stepper motor.


Post-transplant lymphoproliferative disorders after live donor renal transplantation.
The development of post-transplant lymphoproliferative disorders (PTLD) is a well-recognized complication of solid organ transplantation in patients receiving immunosuppressive therapy. The literature on PTLD in live renal allograft recipients is scarce and most of the data pertains to PTLD in cadaveric transplants. As live donor grafts form the mainstay of transplantation programme in India, this study was carried out to define the profile of PTLD in live donor renal allograft recipients. On retrospective evaluation, nine cases of PTLD amongst 1700 live donor allograft recipients from January 1989 to August 2004, were detected at a tertiary care hospital in north India. The clinicopathological features of these cases were evaluated. Mean age at diagnosis of PTLD was 38 yr with median post-transplant latency period of 7 yr. All cases were from extra-renal sites, five being in ileum/jejunum, three in retroperitoneal lymph nodes and one in epididymus. All cases received cyclosporin, azathioprine and prednisolone in varying combinations as immunosuppressive therapy. One case was treated for rejection by anti-thymocyte globulin. Seven patients were seronegative for Epstein-Barr virus at the time of diagnosis. All were B-cell monomorphic PTLD, classifiable as B-cell diffuse large cell lymphomas, with five extranodal and three nodal lymphomas. Management included reduction in immunosuppression, acyclovir therapy, surgical excision and chemotherapy. On follow-up, four patients died, two presented with recurrence, two were in remission and one was lost to follow-up. This study comprising of live related/unrelated renal allograft recipients observed late onset high grade monomorphic PTLD with paucity of early onset polymorphic lesions. Long post-transplant latency period, aggressive behaviour and poor response to treatment necessitate long-term cancer surveillance to facilitate early detection and newer therapeutic strategies to improve the outcome in these patients.


Discovery of potential pancreatic cholesterol esterase inhibitors using pharmacophore modelling, virtual screening, and optimization studies.
Pancreatic cholesterol esterase (CEase) is a serine hydrolase involved in the hydrolysis of variety of lipids and transport of free cholesterol. In this study, pharmacophore hypotheses based on known inhibitors were generated using common feature pharmacophore generation protocol available in Discovery Studio program. The best pharmacophore model containing two hydrogen bond acceptor and three hydrophobic features was selected and validated. It was further used in screening three diverse chemical databases. Hit compounds were subjected to drug-likeness and molecular docking studies. Four hits, namely SEW00846, NCI0040784, GK03167, and CD10645, were selected based on the GOLD fitness score and interaction with active site amino acids. All hit compounds were further optimized to improve their binding in the active site. The optimized compounds were found to have improved binding at the active site. Strongly binding optimized hits at the active site can act as virtual leads in potent CEase inhibitor designing.


Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus.
Andes virus (ANDV) is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated the profile of the pro-inflammatory cytokines IL-1β, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 in serum samples of ANDV-infected patients at the time of hospitalization. The mean levels of circulating cytokines were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, in order to compare 43 serum samples of healthy controls and 43 samples of ANDV-infected patients that had been categorized according to the severity of disease. When compared to the controls, no significant differences in IL-1β concentration were observed in ANDV-infected patients (p = 0.9672), whereas levels of IL-12p70 and IL-21 were significantly lower in infected cases (p = <0.0001). Significantly elevated levels of TNF-α, IFN-γ, IL-10, and IL-6 were detected in ANDV-infected individuals (p = <0.0001, 0.0036, <0.0001, <0.0001, respectively). Notably, IL-6 levels were significantly higher (40-fold) in the 22 patients with severe symptoms compared to the 21 individuals with mild symptoms (p = <0.0001). Using multivariate regression models, we show that IL-6 levels has a crude OR of 14.4 (CI: 3.3-63.1). In conclusion, the serum level of IL-6 is a significant predictor of the severity of the clinical outcome of ANDV-induced disease.


Adherence to Safe Sleep Recommendations by Families With Higher-order Multiples.
More than 95% of higher-order multiples are born preterm and more than 90% are low birth weight, making this group of infants especially vulnerable to sudden infant death syndrome (SIDS). Emerging evidence suggests that families with twins face challenges adhering to the American Academy of Pediatrics (AAP) recommendations to reduce SIDS risks. Adherence to the AAP recommendations in families with higher-order multiples has not been described. This study describes SIDS risk reduction infant care practices for higher-order multiples during the first year of life. Mothers caring for higher-order multiple-birth infants were recruited from an online support group. An online survey was used to assess infant care practices when the infants were first brought home from the hospital as well as at the time of the survey. Ten mothers of triplets and 4 mothers of quadruplets responded. Less than 80% of the mothers practiced "back to sleep" immediately postdischarge. Supine sleep positioning decreased over time, particularly during daytime naps. Only 50% of the infants shared the parents' bedroom and approximately 30% bed-shared with their siblings. Sleep-time pacifier use was low. Safe sleep education must include specific questions regarding home sleeping arrangements, encouragement of breast milk feedings, supine positioning, and pacifier use at every sleep for higher-order multiple infants well before discharge in order for parents to plan a safe sleep environment at home. Prospective studies to identify barriers and facilitators can inform future strategies supporting adherence to safe sleep practices for higher-order multiple infants.


[Pan-genomics analysis of 30 Escherichia coli genomes].
A pan-genome describes the full complement of genes in species. It is a superset of all the genes in all the individuals of a species, which is composed of a 'core genome' containing genes present in all individuals, and a 'dispensable genome' containing genes present only in some individuals and individual-specific genes. From pan-genome sight, 30 finished genomes from Escherichia coli were employed to analyze their gene and genome compositions and evaluation in this study. The results indicated that the core genes accounted for about 50% of the total number of genes, while about 146 strain-specific genes existed in the each strain tested. The data suggests that the E. coli pan-genome is vast, and unique genes will continue to be identified when more E. coli genomes are sequenced. After analyzing relationships of the gene conservation, GC content and selection pressure in different strains tested, we found that more conserved genes had a nar-row range of GC content, and they also bear more selection pressure. These results will be helpful for better understanding of the evolution profile of E. coli genome, and the dynamic changes of its gene compositions. The E. coli pan-genome pro-vides useful information for prevention and control of the diseases caused by pathogenic E. coli, and also provides a para-digm for the large-scale analysis of pathogenic bacteria genomes.


Stent graft infixation after venous dislodgement in a patient with femoral posttraumatic arteriovenous fistula.
An arteriovenous fistula (AVF) is an abnormal connection between an artery and a vein which may result from traumatic injury or may occur as congenital abnormality. Stent graft repair through arteriovenous fistula could lead to complications. Endovascular stent graft repair in a 23-year-old patient with posttraumatic superficial femoral arteriovenous fistula was performed to cover a fistula. During the procedure the device migrated through the fistula into the femoral vein. Due to eventual risk of migration to the heart, a prompt decision was made to fix the stent graft with three puncture needles in the common femoral vein region under fluoroscopy guidance. The vascular surgeon was called to perform open surgery. The presented way of treating this rare complication in an extreme and uncommon situation is very efficient, safe and inexpensive.


Squamous cell carcinoma of the anal canal: patterns and predictors of failure and implications for intensity-modulated radiation treatment planning.
Intensity-modulated radiation treatment (IMRT) is increasingly used in the treatment of squamous cell carcinoma of the anal canal (SCCAC). Prevention of locoregional failure (LRF) using IMRT requires appropriate clinical target volume (CTV) definition. To better define the CTV for IMRT, we evaluated patterns and predictors of LRF in SCCAC patients given conventional radiation treatment. We reviewed records of 180 SCCAC patients treated with conventional radiation with or without chemotherapy at our institution between January 1990 and March 2007. All patients received radiation; the median primary tumor dose was 45 Gy. A total of 173 patients also received mitomycin-based chemotherapy. Median follow-up was 40 months. Actuarial 3-year colostomy-free survival was 89% and overall survival (OS) 88%. Actuarial 3-year LRF was 23%. A total of 45 patients had LRF, with 35 (78%) occurring locally in the primary site (25 local only, 10 local and regional); however, 20 (44%) had regional components of failure within the pelvis or inguinal nodes (10 regional only, 10 local and regional). Cumulative sites of LRF (patients may have one or more site of failure) were as follows: primary, 35; inguinal, 8; external perianal, 5; common iliac, 4; presacral, 3; distal rectum, 2; external iliac, 2; and internal iliac, 2. All patients with common iliac failure had cT3 or N+ disease. The observed patterns of failure support inclusion of the inguinal and all pelvic nodal groups in the CTV for IMRT. In patients with advanced tumor or nodal stage, common iliac nodes should also be included in the CTV.


[Anticarcinogenic effect of 20(R)-ginsenoside Rg3 on induced hepatocellular carcinoma in rats].
To explore the anticarcinogenic mechanism of 20(R)-ginsenoside Rg3 in induced liver tumor in SD rat. Thirty-five SD rats with induced hepatocellular carcinoma were divided into a control group and 3 dosage groups according to the dosing levels of 20(R)-ginsenoside Rg3. The tumour volume was measured by MR imaging. The apoptotic rat and S-phase fraction and diploid of tumor cell were measured with flow cytometry. Protein expression of PCNA and TNF were evaluated with immunohistochemistry. There was significant difference in tumour volume between the high dosage group and the control group. The average apoptotic rates were 11.08+/-3.78, 13.57+/-3.34, 27.35+/-16.04 and the S-phase fractions were 23.98+/-9.44, 19.73+/-6.62, 14.09+/-3.48 in the low-, medium-, and high-dosage groups respectively. The apoptotic rate was significantly higher in the high-dosage group than in the medium-dosage group and low-dosage group. Before-after comparison showed that the anti-proliferative effects of 20(R)-ginsenoside Rg3 were significant in three treatment groups. The higher positive rats of protein expression with PCNA and TNF were significant difference in the high-dosage group compared to those in the low-dosage group. No significant difference between the medium-dosage group and the low-dosage group. 20(R)-ginsenoside Rg3 can noticeably inhibit the proliferation of tumor cells, and efficaciously induce the apoptosis and facilitate necrosis of the tumor cells, and there appears to be a dose dependent effect.


cis-acting regulatory elements within gag genes of avian retroviruses.
A cis-acting enhancer element has been detected within the gag gene of several avian retroviruses, including Rous sarcoma virus, Fujinami sarcoma virus, and the endogenous Rous-associated virus-0. A consensus enhancer core sequence, GTGGTTTG, is present in all of these viral genomes, approximately 900 bases downstream from the site of initiation of transcription. When an internal fragment derived from the gag gene of any of these viruses (spanning nucleotides 533 to approximately 1149) was inserted into a plasmid containing the chloramphenicol acetyltransferase (cat) gene under control of the simian virus 40 promoter, 9- or 21-fold enhancement of CAT expression was observed after transfection into mouse L cells and chicken embryo fibroblasts, respectively. This enhancement was not dependent on the position of insertion of the gag fragment into the plasmid. However, there was a strong dependence on orientation, with higher levels of CAT expression in constructs in which the 5' end of the gag fragment was nearest to the promoter, suggesting a possible negative regulatory element at the 3' end of this fragment. Deletion of the 3' end of the insert resulted in a gag fragment, containing nucleotides 533 to 1017, which enhanced expression equally in either orientation. When the gag fragment was inserted into a plasmid containing the cat gene under the control of an intact Rous sarcoma virus long terminal repeat, it induced a two- to threefold increase in CAT activity and CAT mRNA levels. Translation of the gag fragment did not appear to be necessary for the observed enhancement, since two insertional mutations resulting in frameshifts in the gag insert did not affect CAT expression. However, deletion of a 330-base internal fragment from the gag insert restored a basal level of CAT activity. These results suggest that retroviruses have regulatory elements within their genes distinct from those in the long terminal repeats that flank the genes.


[Clinical evaluation of recombinant human G-CSF in children with cancer].
Recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was administered in 69 chemotherapy-induced neutropenic pediatric patients (pts) with malignant tumors. Each pt received two cycles of the same chemotherapy and had neutropenia with absolute neutrophil counts (ANC) less than 500/microliter in the first cycle. Initiating 72 hours after termination of chemotherapy in the second cycle, rG-CSF (2 micrograms/kg/day) was given subcutaneously or intravenously to each pt for 10 days. rG-CSF significantly increased ANC at nadir; 72 +/- 14 vs. 206 +/- 40/microliter (data in the first cycle vs. data in the second cycle, respectively), and reduced the period of neutropenia with ANC less than 500/microliter; 9.7 +/- 0.6 vs. 5.1 +/- 0.6 days, and the period for restoration to ANC greater than or equal to 1,000/microliter after initiation of chemotherapy; 25.5 +/- 0.6 vs 17.5 +/- 0.9 days. rG-CSF did not affect other components of peripheral blood. The number of days with fever greater than or equal to 38 degrees C was significantly reduced by rG-CSF treatment. Neck pain and lumbago were observed in one pt, pollakisuria in one pt, and elevation of the serum levels of LDH and uric acid in one pt, however these were mild to moderate, transient, and resolved without any specific treatment. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for malignant tumors without any serious side effects.


The interaction of oxygen with TiC(001): photoemission and first-principles studies.
High-resolution photoemission and first-principles density-functional slab calculations were used to study the interaction of oxygen with a TiC(001) surface. Atomic oxygen is present on the TiC(001) substrate after small doses of O(2) at room temperature. A big positive shift (1.5-1.8 eV) was detected for the C 1s core level. These photoemission studies suggest the existence of strong O<-->C interactions. A phenomenon corroborated by the results of first-principles calculations, which show a CTiTi hollow as the most stable site for the adsorption of O. Ti and C atoms are involved in the adsorption and dissociation of the O(2) molecule. In general, the bond between O and the TiC(001) surface contains a large degree of ionic character. The carbide-->O charge transfer is substantial even at high coverages (>0.5 ML) of oxygen. At 500 K and large doses of O(2), oxidation of the carbide surface occurs with the removal of C and formation of titanium oxides. There is an activation barrier for the exchange of Ti-C and Ti-O bonds which is overcome only by the formation of C-C or C-O bonds on the surface. The mechanism for the removal of a C atom as CO gas involves a minimum of two O adatoms, and three O adatoms are required for the formation of CO(2) gas. Due to the high stability of TiC, an O adatom alone cannot induce the generation of a C vacancy in a flat TiC(001) surface.


Plasmon-induced transparency in a single multimode stub resonator.
We investigate electromagnetically induced transparency (EIT)-like effect in a metal-dielectric-metal (MDM) waveguide coupled to a single multimode stub resonator. Adjusting the geometrical parameters of the stub resonator, we can realize single or double plasmon-induced transparency (PIT) windows in the plasmonic structure. Moreover, the consistency between analytical results and finite difference time domain (FDTD) simulations reveals that the PIT results from the destructive interference between resonance modes in the stub resonator. Compared with previous EIT-like scheme based on MDM waveguide, the plasmonic system takes the advantages of easy fabrication and compactness. The results may open up avenues for the control of light in highly integrated optical circuits.


The emergence of interest in the ethics of psychological research with humans.
We describe the growth of interest in the ethics of research with human participants based on articles abstracted in Psychological Abstracts and PsycLIT. Interest was low and variable until 1974, after which there was a marked increase in the number of articles published. We explain this emergence of ethical interest in terms of the social climate of concern for human rights in the 1960s and 1970s, the 1973 revision of the American Psychological Association's ethical principles, and the development of federal regulation of research with human participants.


Sexual maturation and productivity of Japanese quail fed graded concentrations of mercuric chloride.
Japanese quail (Coturnix c. japonica) were fed 0, 2, 4, 8, 16, and 32 p.p.m. Hg as mercuric chloride (HgCl2) from the time of hatching up to the age of 1 year. None of the birds manifested any gross signs of mercury poisioning. Food consumption, growth rate, and weight maintenance were unaffected. Initial oviposition tended to occur at a younger age as dietary mercuric chloride increased, e.g., the median age at which egg laying began among hens fed 32 p.p.m. Hg was 6 days younger than for controls. The average rate of egg production was positively related to the concentration of mercuric chloride with the most pronounced differences between treatments occurring among young (less than 9-week-old) hens. Beyond 9 weeks of age production was more uniform among the treatments, but even after 1 year hens on 32 p.p.m. Hg were laying an average of 13.5% more eggs than controls. Rate of egg fertilization was generally depressed for all Hg-treatments above 4 p.p.m. Hatchability of fertilized eggs and eggshell thickness appeared unaffected by mercuric chloride.


Tracing Founder Mutations in Circulating and Tissue-Resident Follicular Lymphoma Precursors.
Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals, suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultradeep sequencing of prediagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, CREBBP lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected BCL2 rearrangements (0/13, P = 0.03 and 0/20, P = 0.007, respectively). CREBBP variants were detectable a median of 5.8 years before FL diagnosis, were clonally selected in FL tumors, and appeared restricted to the committed B-cell lineage. These results suggest that mutations affecting the CREBBP KAT domain are common lesions in FL cancer precursor cells (CPC), with the potential for discriminating subjects at risk of developing FL or monitoring residual disease. Our study provides direct evidence for recurrent genetic aberrations preceding FL diagnosis, revealing the combination of BCL2 translocation with CREBBP KAT domain mutations as characteristic committed lesions of FL CPCs. Such prediagnostic mutations are detectable years before clinical diagnosis and may help discriminate individuals at risk for lymphoma development. This article is highlighted in the In This Issue feature, p. 1275.


Toll-like receptor 9 activation induces expression of membrane-bound B-cell activating factor (BAFF) on human B cells and leads to increased proliferation in response to both soluble and membrane-bound BAFF.
Activation of TLR7 and TLR9 and high serum levels of BAFF have been implicated in the pathogenesis of SLE. However, little is known about the effects of TLR9 activation on BAFF expression by human B cells. We investigated the effect of the TLR9 agonist, CpG-ODN 2006, on the expression of BAFF and its receptors BAFF-R, TACI and BCMA, in isolated B cells from healthy donors. We used RT-PCR, flow cytometry and ELISA to investigate the expression of BAFF, and flow cytometry for BAFF-R, TACI and BCMA. Functional assays assessed the responses of resting and CpG-ODN-activated B cells to exogenous soluble and membrane-bound BAFF. CpG-ODN did not induce BAFF secretion, but increased expression of membrane-bound BAFF on B cells. CpG-ODN also induced the expression of TACI and BCMA, but did not up-regulate BAFF-R expression. In functional studies, CpG-ODN sensitized human B cells to proliferate in response to exogenous BAFF. This effect was inhibited by a blocking antibody against BAFF-R, but was not inhibited by anti-TACI or anti-BCMA antibodies. Membrane-bound BAFF, induced by CpG-ODN, co-stimulated the proliferation of B cells stimulated with anti-IgM in a manner that was dependent on the expression of surface BAFF on the CpG-ODN-treated B cells. TLR9 activation induces expression of membrane-bound BAFF on human B cells and leads to increased proliferation in response to both soluble and membrane-bound BAFF. These data extend our understanding of the role of TLR9 activation on human B cells and provide insights into the mechanisms by which TLR9 may participate in the pathogenesis of SLE.


The relationship between autoimmunity and specific immunotherapy for allergic diseases.
The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1 ± 12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term.


Is undergraduate physiotherapy study a risk factor for low back pain? A prevalence study of LBP in physiotherapy students.
Following reports of high prevalence of low back pain (LBP) in young physiotherapists, we investigated whether LBP was a problem for undergraduate physiotherapy students. Physiotherapy students enrolled in one Australian tertiary institution completed a validated self-administered questionnaire in April 2001, seeking information on LBP prevalence (lifetime, 12 month, one-month, one-week), and its risk factors. The survey incorporated the Nordic back questionnaire, questions on common risks for LBP, and purpose-built questions regarding educational exposures. Univariate logistic regression models were applied to test associations. 72% students responded. LBP prevalence was 69% (lifetime), 63% (12-month), 44% (one-month), 28% (one-week). The risk of LBP increased significantly for students once they completed first year. Being aged 20 or 21 years (final year students) was significantly associated with all measures of LBP, compared with the youngest students. Exposure to tertiary study of greater than two years was associated with lifetime, 12 month and one-month LBP prevalence. Spending more than 20 hours in the past month 'sitting looking down' was significantly associated with one-month LBP prevalence. Similar exposure to 'treating patients' was significantly associated with one-month and one-week LBP prevalence. Physiotherapy students should be alerted to the likelihood of LBP and is potential causes during their training, so that they enter the workforce with reduced risk of LBP. The potential for other undergraduate students to suffer LBP should also be considered.


"Inverse sodium hydride": a crystalline salt that contains H(+) and Na(-).
A crystalline salt has been synthesized that contains H(+) and Na(-) rather than the usual hydride oxidation states of H(-) and Na(+). The key is irreversible encapsulation of H(+) within the cage of 3(6)adamanzane (Adz). The internal proton is kinetically inert to reduction by Na(-) in solution in NH(3)-MeNH(2) mixtures. Synthesis of the sodide is accomplished by a metathesis reaction between Na and AdzH(+)X(-) in which X(-) is a sacrificial anion such as glycolate, isethionate, or nitrate. Reduction or deprotonation of the sacrificial anion forms insoluble byproducts and AdzH(+)Na(-) in solution. After solvent removal, the sodide is dissolved in dimethyl ether and transferred through a frit into a separate chamber for crystallization. The compound was characterized as the sodide by analysis, NMR spectra, and optical absorption spectroscopy.


Real-World Setting Comparison of Nonvitamin-K Antagonist Oral Anticoagulants Versus Vitamin-K Antagonists for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.
Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonvitamin-K oral anticoagulants compared with vitamin-K antagonists in patients with atrial fibrillation. We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonvitamin-K oral anticoagulants versus vitamin-K antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroke, ischemic stroke or systemic embolism, any stroke or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death. In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with vitamin-K antagonists, all 3 nonvitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31-0.63; dabigatran HR, 0.42; 95% CI, 0.37-0.49; rivaroxaban HR, 0.64; 95% CI, 0.47-0.86); similar rates of ischemic stroke and ischemic stroke or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75-1.19 and HR, 1.08; 95% CI, 0.95-1.22 / dabigatran HR, 0.96; 95% CI, 0.80-1.16 and HR, 1.17; 95% CI, 0.92-1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76-1.04 and HR, 0.73; 95% CI, 0.52-1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56-0.75 and HR, 0.63; 95% CI, 0.53-0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42-0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48-0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06-1.36 and HR, 1.24; 95% CI, 1.08-1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77-1.21 and HR, 1.02; 95% CI, 0.54-1.89, respectively). This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity.


Inferior frontal gyrus gray matter volume is associated with aggressive behavior in schizophrenia spectrum disorders.
We aimed to assess potential gray matter (GM) alterations for aggressive patterns of behavior in a sample of in- and outpatients with schizophrenia spectrum disorders. Eighty-four patients previously participating in brain volumetric studies were included. Aggression was assessed using the Modified Overt Aggression Scales (MOAS) based upon review of clinical records of the hospital register. Multiple regression analyses for total MOAS and each MOAS subscale separately were conducted correcting for age, sex, history of addiction, chlorpromazine equivalents, illness duration, and total intracranial volume. Significant effects were reported in two cases; the total MOAS scores and MOAS verbal aggression scores were associated with GM volume in left inferior frontal gyrus. From the demographic/clinical characteristics, only the number of episodes correlated with the subscales and the total MOAS scores. Our results highlight the role of GM volume in left inferior frontal gyri in patients with history of aggression. This evidence ties in well with previous data reporting involvement of these regions in response control and semantic networks.


The Regulatory Network of Sweet Corn (Zea mays L.) Seedlings under Heat Stress Revealed by Transcriptome and Metabolome Analysis.
Heat stress is an increasingly significant abiotic stress factor affecting crop yield and quality. This study aims to uncover the regulatory mechanism of sweet corn response to heat stress by integrating transcriptome and metabolome analyses of seedlings exposed to normal (25 °C) or high temperature (42 °C). The transcriptome results revealed numerous pathways affected by heat stress, especially those related to phenylpropanoid processes and photosynthesis, with 102 and 107 differentially expressed genes (DEGs) identified, respectively, and mostly down-regulated in expression. The metabolome results showed that 12 or 24 h of heat stress significantly affected the abundance of metabolites, with 61 metabolites detected after 12 h and 111 after 24 h, of which 42 metabolites were detected at both time points, including various alkaloids and flavonoids. Scopoletin-7-o-glucoside (scopolin), 3-indolepropionic acid, acetryptine, 5,7-dihydroxy-3',4',5'-trimethoxyflavone, and 5,6,7,4'-tetramethoxyflavanone expression levels were mostly up-regulated. A regulatory network was built by analyzing the correlations between gene modules and metabolites, and four hub genes in sweet corn seedlings under heat stress were identified: RNA-dependent RNA polymerase 2 (RDR2), UDP-glucosyltransferase 73C5 (UGT73C5), LOC103633555, and CTC-interacting domain 7 (CID7). These results provide a foundation for improving sweet corn development through biological intervention or genome-level modulation.


Exploration of the topological properties in a non-Hermitian long-range system.
The asymmetrical long-range hopping amplitudes have a rich influence on the topological properties. Here, a non-Hermitian model including the long-range hopping amplitudes is constructed to explore those properties. It can be found that an extra topological invariantW= 2 emerges as a consequence of the long-range hopping amplitudes. Furthermore, we find that the phaseW= 2 can be directly characterized by the generalized Brillouin zone (GBZ) itself through the concept of the argument principle. Meanwhile, a gapless phase dubbed as topological semimetal phase can be induced by the asymmetrical long-range hopping. Moreover, the physical origin of the topological semimetal phase can be explained by the solutions of eigen-equation. It is also shown that the skin modes exist as long as the GBZ and the Brillouin zone differ from each other. These interesting phases may be realized in an electrical-circuit simulator.


BioMAT: An Open-Source Biomechanics Multi-Activity Transformer for Joint Kinematic Predictions Using Wearable Sensors.
Through wearable sensors and deep learning techniques, biomechanical analysis can reach beyond the lab for clinical and sporting applications. Transformers, a class of recent deep learning models, have become widely used in state-of-the-art artificial intelligence research due to their superior performance in various natural language processing and computer vision tasks. The performance of transformer models has not yet been investigated in biomechanics applications. In this study, we introduce a Biomechanical Multi-activity Transformer-based model, BioMAT, for the estimation of joint kinematics from streaming signals of multiple inertia measurement units (IMUs) using a publicly available dataset. This dataset includes IMU signals and the corresponding sagittal plane kinematics of the hip, knee, and ankle joints during multiple activities of daily living. We evaluated the model's performance and generalizability and compared it against a convolutional neural network long short-term model, a bidirectional long short-term model, and multi-linear regression across different ambulation tasks including level ground walking (LW), ramp ascent (RA), ramp descent (RD), stair ascent (SA), and stair descent (SD). To investigate the effect of different activity datasets on prediction accuracy, we compared the performance of a universal model trained on all activities against task-specific models trained on individual tasks. When the models were tested on three unseen subjects' data, BioMAT outperformed the benchmark models with an average root mean square error (RMSE) of 5.5 ± 0.5°, and normalized RMSE of 6.8 ± 0.3° across all three joints and all activities. A unified BioMAT model demonstrated superior performance compared to individual task-specific models across four of five activities. The RMSE values from the universal model for LW, RA, RD, SA, and SD activities were 5.0 ± 1.5°, 6.2 ± 1.1°, 5.8 ± 1.1°, 5.3 ± 1.6°, and 5.2 ± 0.7° while these values for task-specific models were, 5.3 ± 2.1°, 6.7 ± 2.0°, 6.9 ± 2.2°, 4.9 ± 1.4°, and 5.6 ± 1.3°, respectively. Overall, BioMAT accurately estimated joint kinematics relative to previous machine learning algorithms across different activities directly from the sequence of IMUs signals instead of time-normalized gait cycle data.


Optimal Dwelling Time for Ureteral Stents Placed for Passive Dilation after Impassable Ureteroscopy.
The aim of the study was to determine the correlation between the dwelling time for a ureteral stent placed for passive dilation after impassable ureteroscopy and success and complications. A retrospective evaluation was made of patients who underwent stent placement after impassable ureteroscopy and a repeat ureteroscopy due to kidney stones. A total of 161 patients were included in the study between 2015 and 2022. Demographic, clinical, preoperative, and perioperative data were collected. Logistic regression analyses were performed on the data showing a significant difference in the univariate analyses performed to determine the predictive factors of ureteroscopy after the stent dwelling period in terms of stone-free status and perioperative complications. Stone-free status was achieved in 110 (68.3%) of 161 patients, and perioperative complications were observed in 41 (25.4%). Factors that affected the stone-free status were determined as the dwelling time and the S-ReSC score, while factors affecting perioperative complications were the stent dwelling time and the operation time. The stone-free rates were observed to increase from 46.4% in the first 2 weeks to 72.9% after the 2nd week, an increase of 1.5-fold. Perioperative complications were determined at the rate of 17.5% during the first 5 weeks and increased 2.1-fold to 37.5% after the 5th week. It can be recommended that great care is taken during the stent dwelling period and ureteroscopy should be performed within 5 weeks (14-35 days) but no earlier than 2 weeks, so as not to affect the success of the procedure.


[Antitumor effect of intratumoral administration of a Coriolus preparation, PSK: inhibition of tumor invasion in vitro].
The antitumor effects of biological response modifiers (BRM) in an experimental mouse model, the "double grafted tumor system," were analysed. Intratumoral administration of PSK (polysaccharide Kureha), a Coriolus preparation into primary tumor induced a cure of not only the primary solid tumor but also the metastatic, distant tumor. The effect of PSK on in vitro invasion by murine RL male-1 leukemia cells was studied using Biocoat Matrigel Invasion Chamber (Becton Dickinson Labware). We determined the ability of tumor cells to penetrate matrigel-coated filters in the presence or absence of PSK. PSK (100 micrograms/ml) reduced to half the number of invasive tumor cells for 3 hr incubation. PSK inhibited tumor cell invasion of matrigel-coated filters in a dose-dependent manner. Matrigel includes laminin, collagen, fibronectin and heparan sulfate proteoglycan. It is possible, therefore, that PSK may inhibit enzymes which digest the components of basement membranes, extra cellular matrices (ECM). This phenomenon suggests that PSK also inhibits metastatic activity of tumor cells in vivo.


Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.
Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.


Perception of distorted "R" sounds in the synthesized speech of children and adults.
Adult and Child manifolds were generated by synthesizing 5 X 5 matrices of /Cej/ type utterances in which F2 and F3 frequencies were systematically varied. Manifold stimuli were presented to 11 graduate-level speech-language pathology students in two conditions: (a) a rating condition in which stimuli were rated on a 4-point scale between good /r/ and good /w/; and (b) a labeling condition in which stimuli were labeled as "R," "W," "distorted R," or "N" (for none of the previous choices). It was found that (a) stimuli with low F2 and high F3 frequencies were rated 1.0-1.4; those with high F2 and low F3 frequencies were rated 3.6-4.0 were labeled as "R"; (c) none of the Child manifold stimuli were labeled as distorted "R" and one of the Adult manifold stimuli approached a level of identification that approached the percentage of identification for "R" and "W"; and (d) rating and labeling tasks were performed with a high degree of reliability.


Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump.
Administration sets are delivery tools for the direct application of drugs into the body and are composed of a spike, a drip chamber, tubes, Luer adapters (connectors), a needle cover for protection, and other accessories. Drug sorption to tubes of administration sets is a critical issue in terms of safety and efficacy. Although drug sorption is an important factor in the quality of an administration set, there are no standard evaluation methods for the regulation of drug sorption to the tubes. Here, we describe an evaluation protocol for drug sorption to tubes of administration sets. Tubes made of polyvinyl chloride (PVC)- and non-PVC-based polymeric materials were cut to 1 m in length. Diazepam and tacrolimus were used as model drugs. In the kinetic sorption study, we selected the drug concentration and flow rate based on the clinical usage of these drugs. After the dilution of each drug in a glass bottle, the diluted drug solution was delivered through tubes of administration sets using a pump. Samples were collected in amber vials at appropriate time points and the drugs were analyzed using high-performance liquid chromatography. Drug concentrations and sorption levels to tubes of the administration sets were calculated. Acceptable criteria to ensure the quality of administration sets are recommended.


Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera.
Technetium-99m-teboroxime is characterized by a high extraction fraction over a wide range of blood flow rates, rapid myocardial clearance and avid hepatic uptake. This study determined the imaging parameters and examined the clinical efficacy of a rapid back to back adenosine stress/rest teboroxime myocardial perfusion SPECT protocol using a triple-detector camera. Acquisition parameters were determined using cardiac phantom studies which were then applied in SPECT studies of 51 catheterized patients (22 with prior myocardial infarction) and 20 patients with a "low" (7.9% +/- 4.3%) likelihood of coronary artery disease. Technetium-99m-teboroxime (20-25 mCi) was injected at the third minute of adenosine infusion. Teboroxime (20-25 mCi) was also injected at rest, 15 min later. Stress followed by rest SPECT were completed within 25 min using a triple-detector camera and sequential, 1-min continuous rotations in alternating directions. Summed raw data from the first to second (1-2 min), second to third (2-3 min) and second to fifth (2-5 min) minutes of imaging following stress teboroxime injection were reconstructed and compared for image quality, degree of liver interference, and accuracy for diagnostic efficacy. In a subgroup of 30 patients, 2-8-min summed images were also reconstructed to compare this more conventional imaging protocol with our rapid acquisition. Image quality was fair to good in 75% of the 1-2-min, 84% of the 2-3-min and 2-5-min studies and 53% of the 2-8-min scans. The frequency of severe liver interference appeared to increase with the duration of imaging time (1-2 min: 3%; 2-3 min: 7%; 2-5 min: 8%) and was greatest (30%, p = 0.08) with 2-8-min images. Three patients (4%) had uninterpretable studies due to intense hepatic uptake. Overall sensitivity (95%) and specificity (71%) were equal for the 2-3-min and 2-5-min stress images and appeared better than in the 1-2-min images (84% and 57%, respectively). For the 2-8-min scans, vessel sensitivity (69%) and specificity (63%) appeared poorer than with 2-3-min studies (83% and 81%, respectively). Normalcy rates were 89% for the 2-3-min and 2-5-min and 79% for 1-2-min images. The back to back adenosine stress/rest teboroxime SPECT can be performed in 30 min using a triple-detector camera. Although overall high sensitivity and normalcy rates were achieved, the protocol is technically demanding. Interference due to intense liver uptake remains problematic.