Fractionated illumination significantly improves the response of superficial basal cell carcinoma to aminolevulinic acid photodynamic therapy.
Photodynamic therapy (PDT) of superficial basal cell carcinoma (sBCC) using topical 5-aminolevulinic acid (ALA) and a light fluence of 75-100 J cm(-2) yields unsatisfactory long-term results. In several animal models, illumination with two light fractions 2 hours apart was considerably more effective than single illumination. Response is further enhanced if the fluence of the first light fraction is reduced, although the cumulative fluence is maintained. We compared the response of sBCC to a single illumination and 2-fold illumination scheme in which two light fractions of 20 and 80 J cm(-2) are performed 4 and 6 hours after the application of a single dose of 20% ALA. We randomly assigned 154 patients with a total of 505 primary sBCC into two treatment groups. Two hundred and forty-three lesions were treated using a single illumination of 75 J cm(-2) at a fluence rate of 50 mW cm(-2). Fractionated PDT, at the same fluence rate, was performed on 262 lesions. The complete response (CR) following a 2-fold illumination scheme is significantly greater than that following a single light fraction (P=0.002, log-rank test). Twelve months after therapy, CR rate to a 2-fold illumination is 97%, whereas the CR to a single illumination is 89%.


A TRS-80-based system for the control of behavioral experiments.
A TRS-80-based system is described for controlling and recording events from operant chambers. The system features a TRS-80 microprocessor with 32 K RAM, a floppy disk drive, an LVB optical interface, a printer, and a user-oriented program (Operant Protocol System, OPS). The LVB interface system is capable of up to 128 independent input/output operations for each of up to 8 boxes. The system uses assembly language routines for real-time control and event recording of up to 8 boxes simultaneously. BASIC is used to obtain user input and deliver data output in an interactive fashion. Advantages include dependable hardware, extensively documented and tested software, relative inexpensiveness, and standard-deviation-based variable schedules.


SERCA Overexpression Improves Mitochondrial Quality Control and Attenuates Cardiac Microvascular Ischemia-Reperfusion Injury.
Despite significant advances in the treatment of myocardial ischemia-reperfusion (I/R) injury, coronary circulation is a so far neglected target of cardioprotection. In this study, we investigated the molecular mechanisms underlying I/R injury to cardiac microcirculation. Using gene delivery, we analyzed microvascular protective effects of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) on the reperfused heart and examined the role of SERCA in regulating mitochondrial quality control in cardiac microvascular endothelial cells (CMECs). Our data showed that SERCA overexpression attenuates lumen stenosis, inhibits microthrombus formation, reduces inflammation response, and improves endothelium-dependent vascular relaxation. In vitro experiments demonstrated that SERCA overexpression improves endothelial viability, barrier integrity, and cytoskeleton assembly in CMECs. Mitochondrial quality control, including mitochondrial fusion, mitophagy, bioenergetics, and biogenesis, were disrupted by I/R injury but were restored by SERCA overexpression. SERCA overexpression also restored mitochondrial quality control by inhibiting calcium overload, inactivating xanthine oxidase (XO), and reducing intracellular/mitochondrial reactive oxygen species (ROS). Administration of exogenous XO or a calcium channel agonist abolished the protective effects of SERCA overexpression on mitochondrial quality control and offset the beneficial effects of SERCA overexpression after cardiac microvascular I/R injury. These findings indicate that SERCA overexpression may be an effective approach to targeting cardiac microvascular I/R injury by regulating calcium/XO/ROS signaling and preserving mitochondrial quality control.


Telomerase inhibition, oligonucleotides, and clinical trials.
Telomerase is expressed in most types of tumors but not in most somatic cells. This observation has led to two hypotheses; (i) telomerase activity is necessary for the proliferation of cancer cells; and (ii) telomerase inhibitors are a powerful strategy for cancer chemotherapy. Testing the latter hypothesis requires the development of potent and selective inhibitors of telomerase and their testing in clinical trials. Assaying the efficacy of telomerase inhibitors will not be simple because telomere erosion will be slow and antiproliferative effects will probably require weeks to become apparent. This review will describe the properties of 2'-O-alkyl oligonucleotide inhibitors of telomerase. Oligonucleotides that block expression of other cancer targets have favorable pharmacokinetic properties and are already in clinical trials. This experience is likely to facilitate clinical trials of anti-telomerase oligomers.


Targeted Therapies for Advanced Oesophagogastric Cancer: Recent Progress and Future Directions.
The genomic landscape of oesophagogastric (OG) cancer is highly complex. The recent elucidation of some of the pathways involved has suggested a number of novel targets for therapy. This therapy is urgently required as with conventional chemotherapy regimens patients with advanced OG cancer still have a median overall survival of under a year. This review outlines the rationale for the current treatment of OG cancer with chemotherapy and describes both previously conducted and ongoing clinical trials of novel agents in this area. The targets and associated treatments discussed include HER-2, EGFR, VEGF, c-Met, FGFR-2, PI3K, mTOR andIGF-1. To date only two targeted treatments, trastuzumab and ramucirumab, have become part of the treatment paradigm for OG cancer, partly due to difficulties in defining predictive biomarkers in this disease. However, there are a number of promising drugs in the pipeline and this article seeks to describe these and other potential novel approaches including targeting DNA repair deficiencies and the immune system.


Insights into the catalytic mechanism of glutathione S-transferase: the lesson from Schistosoma haematobium.
Glutathione S-transferases (GSTs) are involved in detoxification of xenobiotic compounds and in the biosynthesis of important metabolites. All GSTs activate glutathione (GSH) to GS(-); in many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulfur of GSH. The high-resolution structure of GST from Schistosoma haematobium revealed that the catalytic Tyr occupies two alternative positions, one external, involving a pi-cation interaction with the conserved Arg21, and the other inside the GSH binding site. The interaction with Arg21 lowers the pK(a) of the catalytic Tyr10, as required for catalysis. Examination of several other GST structures revealed the presence of an external pocket that may accommodate the catalytic Tyr, and suggested that the change in conformation and acidic properties of the catalytic Tyr may be shared by other GSTs. Arginine and two other residues of the external pocket constitute a conserved structural motif, clearly identified by sequence comparison.


Intraoperative ultrasonography-guided surgery for malignant soft tissue tumor.
A clear surgical margin is crucial for preventing the recurrence of soft tissue sarcomas (STSs). Recognizing the tumor border is difficult when the STS is impalpable or ill-defined. Ultrasonography (US) is a widely used diagnostic device that can visualize certain tumors intraoperatively. However, its usefulness for intraoperatively assessing STSs is unclear and was investigated here. Our study comprised 19 patients with STSs that were impalpable, ill-defined, or beneath the fascia. All patients underwent intraoperative US (IOUS), with follow-up times ranging from 5 to 103 months (mean, 49 months). The mean age of the study participants was 56 years (range, 25-83 months). The most common histological diagnosis was undifferentiated pleomorphic sarcoma (UPS) (nine patients). The mean tumor size was 51 mm (range, 7-126 mm). According to the residual tumor classification, 18 tumors were microscopically negative (R0), including seven close to the fascia, and one was microscopically positive (R1). Local recurrence occurred in two cases (both classified as R0). The recurrence-free survival rate was 88.9% in 5 years. IOUS-guided surgery is useful for visualizing STSs. Using this technique, STSs can be precisely localized, evaluated, and excised.


Evidence for intracellular histamine liberation in isolated rat mast cells.
The beta-adrenoceptor blocking drug exaprolol liberated histamine from isolated rat mast cells in a dose- and time-dependent way. Histamine was liberated within seconds and was not followed by a parallel granule liberation. The inhibition of histamine liberation was induced with low temperature, low pH, high concentration of Ca2+, TTD, suramin and EDTA. Subcellular distribution of 3H-exaprolol demonstrated a quantitative relationship between histamine depletion against exaprolol uptake in isolated rat mast cell granules. A nonspecific mechanism of action in the effect of exaprolol on mast cells is discussed. It is proposed that the drug acts on mast cells due to the direct and indirect ion exchange mechanism resulted in disproportion between histamine and granule liberation.


Negotiating the maze of biotech "tool patents".
Circumventing existing patents may be a shortcut to getting your recombinant protein to market.


Measurement of fatty acid oxidation in premature newborn infants with the 13C-triolein breath test.
The 13C-triolein breath test is a method giving evidence of extent and rate of fatty acid oxidation in newborn infants on parenteral nutrition. The test has the special advantage of being non-invasive. Triolein labeled with the stable carbon isotope 13C and emulsified in soybean-oil is used as a tracer. 10 mg of 13C triolein per kg body weight are administered intravenously. The 13CO2 resulting from the fatty acid oxidation is analysed in expired breath by ratio-mass-spectrometry. The calculated 13C elimination is representative of the rate of fatty acid oxidation during the examination period. First studies on 15 premature infants have shown that an average of 27.0 +/- 1.8% of the dose administered is oxidized within 4 h. The present results suggest that the oxidation rate may be related to the maturity of the prematurely born infants.


Oncogenic Ras deregulates cell-substrate interactions during mitotic rounding and respreading to alter cell division orientation.
Oncogenic Ras has been shown to change the way cancer cells divide by increasing the forces generated during mitotic rounding. In this way, RasV12 enables cancer cells to divide across a wider range of mechanical environments than normal cells. Here, we identify a further role for oncogenic Ras-ERK signaling in division by showing that RasV12 expression alters the shape, division orientation, and respreading dynamics of cells as they exit mitosis. Many of these effects appear to result from the impact of RasV12 signaling on actomyosin contractility, because RasV12 induces the severing of retraction fibers that normally guide spindle positioning and provide a memory of the interphase cell shape. In support of this idea, the RasV12 phenotype is reversed by inhibition of actomyosin contractility and can be mimicked by the loss of cell-substrate adhesion during mitosis. Finally, we show that RasV12 activation also perturbs division orientation in cells cultured in 2D epithelial monolayers and 3D spheroids. Thus, the induction of oncogenic Ras-ERK signaling leads to rapid changes in division orientation that, along with the effects of RasV12 on cell growth and cell-cycle progression, are likely to disrupt epithelial tissue organization and contribute to cancer dissemination.


Integrating traditional ecological knowledge into habitat restoration: implications for meeting forest restoration challenges.
Traditional ecological knowledge (TEK) helps tribal communities adapt to socio-ecological changes, improving the long-term sustainability of their livelihood strategies and fostering social-ecological resilience. TEK provides thorough understanding of ecosystem dynamics, as well as how they relate to societal norms, practices, and resource use patterns. The integrity of TEK is often in jeopardy due to changes in belief systems, regional languages, traditional ways of subsistence, and disruption of traditional social-ecological systems. Landscape restoration has the ability to promote self-determination while safeguarding the livelihoods, beliefs, cultural, and biodiversity of indigenous peoples. However, there is a substantial knowledge gap on how TEK might aid ecosystem restoration, particularly in elephant corridors. The current study focused on gathering traditional ecological knowledge on the woody tree species from the Dering-Dibru Saikhowa Elephant Corridor using semi-structured interviews, group discussions, and direct observations. The acquired data were applied to heat map cluster analysis and ordination techniques using R software version 4.0.0. Traditional usage information of 31 tree species utilized for food, fodder, timber, fuelwood, medicinal, and livelihood by local people was gathered. Most of the species utilized locally belonged to the families Combretaceae and Fabaceae. The species were classified into single, double, or multi-uses based on the extent of utilization. Azadirachta indica, Phyllanthus emblica, and Syzygium cumini (six each) had the highest utilization, while Mesua ferrea had the lowest. Chionanthus ramiflorus, Artocarpus heterophyllus, and Dillenia indica were among the plants valuable to wildlife, providing both forage and habitat for a wide variety of birds and animals. Artocarpus heterophyllus, Averrhoa carambola, Mangifera indica, P. emblica, Psidium guajava, and S. cumini were among the plants important for the livelihoods of the local community. Our findings demonstrated that local people were knowledgeable about the plant species to use as pioneer species, such as Bombax ceiba, Albizia lebbeck, D. indica, S. cumini, P. emblica, Lagerstroemia speciosa, and Alstonia scholaris, for habitat restoration in a diverse habitat. We classified the habitat of the enlisted species into different categories, and two clusters (clusters 1 and 2) were identified based on the similarity of woody species in different habitats. We prioritized multiple tree species for eco-restoration using the information collected through TEK. We planted 95,582 saplings on 150 hectares in the Dering-Dibru Saikhowa Elephant Corridors' degraded habitat patches, which will serve as future reference site for landscape rehabilitation. Out of total saplings planted, 56% of the species were linked to native communities through ethnobotanical uses, as well as providing connectivity and habitat for elephant movement, 16% of all woody species are pioneer species to colonize a degraded habitat, 15% of all woody species are preferred food and foraging by wildlife, and 13% of the species as a source of livelihood for local people, incorporating social, economic, cultural, and biodiversity benefits into the restoration framework. The current study also provides insights how the TEK can assist with aspects of ecological restoration, from reference ecosystem reconstruction and adaptive management through species selection for restoration, monitoring, and evaluation of restoration effectiveness.


Nonchemotherapy drug-induced agranulocytosis in elderly patients: the effects of granulocyte colony-stimulating factor.
Elderly patients with nonchemotherapy drug-induced agranulocytosis present commonly with severe infections, and have a mortality of at least 20%. We studied whether granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor that shortens the duration of neutropenia, is useful in these patients. We studied 54 patients > or =65 years of age who had drug-induced agranulocytosis, some of whom had been treated with G-CSF. We determined the times until hematologic recovery (defined as a neutrophil count >1.5 x 10(9)/L), tolerance of G-CSF, and clinical outcomes. Of the 54 patients, 20 received G-CSF. Two patients who had not been treated with G-CSF died of uncontrolled septic shock and extensive pneumonia. The mean (+/- SD) time until hematologic recovery was significantly less in patients treated with G-CSF (6.6 +/- 3.9 days vs. 8.8 +/- 4.9 days, P <0.04). Compliance with G-CSF therapy was good; only mild flu-like symptoms and transient bone pain were reported in 12 patients. Our findings suggest that G-CSF therapy may be beneficial in the management of drug-induced agranulocytosis in elderly patients.


UPLC-Q-TOF/MS-based screening and identification of the main flavonoids and their metabolites in rat bile, urine and feces after oral administration of Scutellaria baicalensis extract.
Traditional Chinese Medicines (TCMs) are increasingly used in combination with Western medicine. Scutellaria baicalensis Georgi (Lamiaceae) is a widely used TCM in treating various diseases. However, the in vivo metabolism of its main bioactive flavonoids, baicalin, baicalein, wogonoside and wogonin, needs further study. A systematic method based on ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique combined with Metabolynx(TM) software was developed to speculate the metabolites and excretion profiles of the main flavonoids in S. baicalensis extract in rats bile, urine and feces samples after oral administration of the extract. Four parent components and a total of 15 metabolites were tentatively detected in vivo. All metabolites were detected including sulfate and glucuronide conjugates, hydroxylated, methylated, acetylated and deoxygenated products. Twelve metabolites were from the rat urine, five from the feces and two from the bile. Among them, several products were reported firstly. The research provided useful information for further study of the pharmacology and mechanism of action of S. baicalensis extract in vivo and a proposed method which could develop an integrated template approach to analyze screening and identification of biological samples after oral administration of TCMs.


Rate and predictors of prescription of lumacaftor - Ivacaftor in the 18 months following approval in the United States.
Lumacaftor-ivacaftor (LUM-IVA) was approved in the US in 2015 for patients with CF aged >12 homozygous for the delF508 mutation, and patients aged 6 to 12 in 2016. To examine the rate of initial LUM-IVA prescriptions following approval. We compared patients eligible for LUM-IVA in the CF Foundation Patient Registry with and without prescriptions in 2015-2016. 5534 (53%) eligible patients had reported prescriptions. Prescription rate in children ages 6-11 was 19% and 61% among patients ≥12 years old. Individuals ≥12 with prescriptions more likely observed among those with private insurance, clinical trial participation, ages 18-30, FEV1 < 90%, more pulmonary exacerbations, and more use of chronic medications. LUM-IVA uptake was less rapid than what was previously observed for ivacaftor, a CFTR modulator approved for a different population. Age, insurance status, disease severity and use of other therapies differed in those prescribed LUM-IVA in the initial post-approval period.


Intraoperative carotid arteriography. A comparison of two techniques.
Routine intraoperative completion carotid arteriography was performed in 225 patients from January 1980 to December 1985 to detect technical problems. In the first 100 patients, standard common carotid artery puncture was used. In the last 125 patients, catheter technique through the superior thyroid artery was compared with the needle technique to evaluate quality of images, completeness of the study, number of exposures required, and complications from these two techniques. The needle technique resulted in complete visualization of the extracranial and intracranial circulations in 94 patients (94 percent). The catheter technique was similarly successful in 123 of 125 patients (98 percent). The proportions of complete visualization were not statistically different in the two groups (p = 0.16). Six patients (6 percent) in the needle technique group and three patients (2 percent) in the catheter technique group required multiple exposures. When the complications incurred by the two techniques were compared, there was no statistical difference between the two techniques (p = 0.39). Two complications occurred in the needle technique group (2 percent), one resulting in dissection and the other, extravasation. There were no complications in the catheter technique group. Due to technical ease of performance, the catheter technique is preferred, although statistical data did not reveal superiority of one technique over the other.


A label-free fluorescent aptasensor for selective and sensitive detection of streptomycin in milk and blood serum.
Sensitive and fast detection of antibiotic residues in animal derived foods and blood serum is of great interest. In this study a fluorescent aptasensor was designed for selective and sensitive detection of streptomycin (STR) based on Exonuclease III (Exo III), SYBR Gold and aptamer complimentary strand. In the absence of STR, the fluorescence intensity is weak. Upon addition of STR, the aptamer binds to its target, leading to release of complementary strand from aptamer and more protection against Exo III function. Following addition of SYBR Gold, a strong fluorescence intensity is obtained. This aptasensor showed a high selectivity toward STR with a limit of detection (LOD) as low as 54.5 nM. The validity of the procedure and applicability of the aptasensor were successfully assessed by detection of STR in a spiked milk and blood serum without interference from the sample matrix.


1-, 3-, and 5-year survival among early-stage lung cancer patients treated with lobectomy vs SBRT.
Lobectomy has traditionally been recommended for fit patients diagnosed with early-stage non-small-cell lung cancer (NSCLC). Recently, however, stereotactic body radiotherapy (SBRT) has been introduced as an alternative treatment option. The purpose of this investigation is to compare survival outcomes for individuals with stage I/II NSCLC treated with lobectomy vs SBRT. This retrospective study included 191 patients (100 surgery, 91 SBRT) identified through the Lung Cancer Evaluation Center, Stony Brook, NY, between 2008 and 2012. Survival and recurrence rates were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models to adjust for possible confounders. A subset of cases was propensity-matched to address potential differences in health status between groups. 1-, 3-, and 5-year survival outcomes were significantly better among patients undergoing lobectomy vs SBRT. Survival rates at 3 years were 92.8% and 59.0% (p<0.001) in the 2 groups, respectively. Propensity-matched analyses indicated similar findings. Recurrence rates were likewise lower among patients undergoing surgery (7.1% vs 21.0%, p<0.01 at 3 years); however, statistical significance was not maintained in the propensity-matched analysis. These findings add to a growing evidence base supporting the use of lobectomy vs SBRT in the treatment of lung cancer among healthy, early-stage NSCLC patients.


Molecular cloning and the COOH-terminal processing of gp64, a putative cell-cell adhesion protein of the cellular slime mold Polysphondylium pallidum.
The cellular slime mold Polysphondylium pallidum expresses a cell surface glycoprotein (referred to as gp64), which seems to be implicated in cell-cell adhesion. We identified a near full-length gp64 cDNA (1,104 base) upon screening a P. pallidum lambda gt11 library with a monoclonal antibody. The open reading frame encodes a protein of 320 amino acids with a molecular mass of 32,752 Da; the protein includes hydrophobic segments at both a NH2- and a COOH-terminal ends. By an Edman degradation analysis of S-pyridylethylated gp64 and its COOH-terminal peptide, it was found that the NH2- and COOH-terminal segments are both removed from the precursor protein of gp64. The COOH-terminal segment was isolated from a lysyl endopeptidase digest of gp64 by an affinity method. The COOH-terminal segment was identified at positions 266-279 in the primary sequence deduced from the cDNA sequence. The mature gp64 consisted of 279 amino acid residues and extremely rich in Cys residues (36 Cys/279 amino acids = 12.9%). Although there was already maximal accumulation of gp64 mRNA in vegetative cells, the protein reached a maximal level during aggregation stage, decreased, and then leveled off through the developmental cycle.


Multi-membrane hydrogels.
Polysaccharide-based hydrogels are useful for numerous applications, from food and cosmetic processing to drug delivery and tissue engineering. The formation of hydrogels from polyelectrolyte solutions is complex, involving a variety of molecular interactions. The physical gelation of polysaccharides can be achieved by balancing solvophobic and solvophilic interactions. Polymer chain reorganization can be obtained by solvent exchange, one of the processing routes forming a simple hydrogel assembly. Nevertheless, many studies on hydrogel formation are empirical with a limited understanding of the mechanisms involved, delaying the processing of more complex structures. Here we use a multi-step interrupted gelation process in controlled physico-chemical conditions to generate complex hydrogels with multi-membrane 'onion-like' architectures. Our approach greatly simplifies the processing of gels with complex shapes and a multi-membrane organization. In contrast with existing assemblies described in the literature, our method allows the formation of free 'inter-membrane' spaces well suited for cell or drug introduction. These architectures, potentially useful in biomedical applications, open interesting perspectives by taking advantage of tailor-made three-dimensional multi-membrane tubular or spherical structures.


Multi-residue determination of 10 selected new psychoactive substances in wastewater samples by liquid chromatography-tandem mass spectrometry.
New psychoactive substances (NPSs) have become increasingly popular in recent years. The analysis of these substances in influent wastewater (IWW) can be used to track their use in communities. In addition, an evaluation of the amount of NPSs released to the aquatic environment can be performed through the analysis of effluent wastewater (EWW). This study presents the development, validation and application of an analytical methodology, based on solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the determination of 10 NPSs in IWW and EWW. Synthetic cannabinoids, cathinones, piperazines and pyrrolidophenones are included among the target analytes. To the authors' knowledge, it is the first time that eight out of these substances (4'-methylpyrrolidinobutyrophenone (MPPP), a-pyrrolidinopentiophenone (a-PVP), 2-[(1S,3R)-3-hydroxycyclohexyl]-5-(2-methyl-2-octanyl) phenol (CP47,497), (1-naphthyl(1-pentyl-1H-indol-3-yl) methanone (JWH-018), (1-butyl-1H-indol-3-yl)(1-naphthyl) methanone (JWH-073), (4-ethyl-1-naphthyl)(1-pentyl-1H-indol-3-yl) methanone (JWH-210), (4-methyl-1-naphthyl) (1-pentyl-1H-indol-3-yl) methanone (JWH-122) and 2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl) ethanone (JWH-250)) are investigated in wastewater. The optimized conditions for the analysis of this set of compounds included a SPE clean-up step using a polymeric sorbent and the use of a pentafluorophenyl (PFP) chromatographic column. Despite the broad range of physicochemical properties of the analytes the method allowed acceptable absolute recoveries (40-109%) for all the studied compounds at different levels of concentration. Low method limits of detection (MLODs) were achieved, ranging between 0.3 and 10 ng/L except for BZP and CP47,497 (20 and 23 ng/L, respectively), allowing a reliable and accurate quantification of the analytes. The method was successfully applied to the analysis of IWW and EWW samples from five wastewater treatment plants (WWTPs) located in Santorini Island (a highly touristic resort in Greece). Four out of 10 compounds (a-PVP, CP47,497, JWH-122 and JWH-210) were detected at least in one sample, being the first evidence of their presence in wastewater. CP47,497 was the most ubiquitous and abundant compound, showing concentrations up to 634 ng/L in some cases.


Medical evaluation of living kidney donors with nephrolithiasis: a survey of practices in the United States.
A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. 49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.


Multiple peptide hormone producing adenocarcinoma of lung with neurotensin and CRF-like immunoreactivity.
A pulmonary cancer of a 43 year-old-man was classified according to WHO-criteria as a poorly differentiated adenocarcinoma because of demonstration of mucinous substances in tumor cells and in rarely occurring acinar lumina. Immunohistochemical reactivity for several peptide hormones was detected in the predominant solid parts of the carcinoma. In many tumor cells an immunoreactivity to neurotensin, bombesin and - according to the elevated serum levels - to ACTH, CRF and calcitonin was found. Therefore the present lung cancer must be defined as a combined carcinoma composed of mucous producing and endocrine cell types. Because peptide hormone production is not restricted to the classical "neuro"-endocrine lung tumors, the histogenesis of this heterogeneous lung cancer is discussed.


A meta-analytic inquiry into the relationship between selected risk factors and problem behavior.
Identifying the predictors of problem behavior is essential both for understanding the causes of such behavior and for preventing it. Although a great deal of research has sought to identify the factors predictive of problem behavior, much of the research to date has been correlational and tells us little about causality. This study attempts to improve on the correlational research by applying meta-analytic techniques to existing experimental and quasi-experimental studies of school-based prevention. The following 3 risk factors were examined: academic performance, bonding to school, and social competency skills. The most convincing evidence of a relationship between risk and problem behavior was found for bonding to school. Positive changes in attachment and commitment to school resulting from the preventive interventions were consistently accompanied by positive changes in problem behavior. Preventive interventions that produced improvements in academic performance produced moderate improvements in problem behavior. With regard to social competence, the association depended in large part on the type of measure used to assess social competency skills. Changes in self-report measures of social competency were unrelated to changes in problem behavior, whereas a strong positive correlation was observed between changes in ratings and observations of social competency by others and improvements in problem behavior.


Global dynamics of a multi-strain SEIR epidemic model with general incidence rates: application to COVID-19 pandemic.
This paper investigates the global stability analysis of two-strain epidemic model with two general incidence rates. The problem is modelled by a system of six nonlinear ordinary differential equations describing the evolution of susceptible, exposed, infected and removed individuals. The wellposedness of the suggested model is established in terms of existence, positivity and boundedness of solutions. Four equilibrium points are given, namely the disease-free equilibrium, the endemic equilibrium with respect to strain 1, the endemic equilibrium with respect to strain 2, and the last endemic equilibrium with respect to both strains. By constructing suitable Lyapunov functional, the global stability of the disease-free equilibrium is proved depending on the basic reproduction number R 0 . Furthermore, using other appropriate Lyapunov functionals, the global stability results of the endemic equilibria are established depending on the strain 1 reproduction number R 0 1 and the strain 2 reproduction number R 0 2 . Numerical simulations are performed in order to confirm the different theoretical results. It was observed that the model with a generalized incidence functions encompasses a large number of models with classical incidence functions and it gives a significant wide view about the equilibria stability. Numerical comparison between the model results and COVID-19 clinical data was conducted. Good fit of the model to the real clinical data was remarked. The impact of the quarantine strategy on controlling the infection spread is discussed. The generalization of the problem to a more complex compartmental model is illustrated at the end of this paper.


A weakly tumorigenic phenotype with high MHC class-I expression is associated with high metastatic potential after surgical removal of the primary murine fibrosarcoma.
We have examined the metastatic capacity of different clones of a chemically induced fibrosarcoma GR9. These clones have previously been characterized for their H-2 class-I and class-II phenotype, NK sensitivity and local tumor growth. Our present data show that clones which express low amounts of H-2 class-I antigens are poorly metastatic in a post-surgical spontaneous metastasis assay, while those expressing high levels of class-I antigens possess a high metastatic capacity. These results correlate inversely with local growth patterns of the clones. High metastatic capacity was associated with resistance to NK cells. In an experimental metastasis assay, based on intravenous administration of in vitro carried GR9 clones to syngeneic BALB/c mice, an opposite result to the post-surgical assay was obtained. Gamma-IFN treatment of B9 clones (H-2-deficient) enhanced H-2 class-I expression and diminished experimentally induced metastases. Metastatic colonies, from the spontaneous metastasis assay, obtained from different organs, showed changes in the ratio H-2K/H-2D. There was a tendency for down-regulation of the expression of H-2K molecules in H-2-positive clones and for up-regulation of H-2D expression in H-2-negative clones.


Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine.
Graft failure is a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). We used a nonmyeloablative conditioning regimen consisting of the lympho-depleting humanized CD52-antibody Campath-1H and fludarabine to rescue 12 consecutive children age 9 months to 17 years with engraftment failure after initial myeloablative HSCT. Primary diagnoses included lymphohematologic malignancies (n=6), severe combined immunodeficiency syndrome (SCID) (n=4), and metabolic diseases (n=2). The same stem cell donor was used as for the primary graft: mismatched family member (n=7), matched unrelated donor (n=4), or matched related donor (n=1). The patients received doses of CD34+ cells that did not significantly differ from those used in the initial, failed transplant. At a median follow-up of 51 months (range, 4 to 84 months), 6 of 6 patients with nonmalignant diseases and 4 of 6 patients with malignancy were alive. Two patients died, 1 patient from pulmonary toxicity and 1 from relapse, at 51 days and 8 months posttransplantation, respectively. All 12 patients initially achieved sustained neutrophil engraftment and complete donor chimerism by day 28. Six patients received donor lymphocyte infusion (DLI) after "rescue" therapy to maintain donor chimerism. At 6 months, 4 patients had complete donor cell engraftment, 4 had 15% to 89% stable donor chimerism, and 3 had developed secondary graft failure. This conditioning regimen was generally well tolerated; 4 of the 12 patients never became neutropenic, and 9 never became thrombocytopenic. Only 1 patient developed graft-versus-host disease (GVHD; grade 1), and none had chronic GVHD. Thus, the regimen that we describe can be used with minimal toxicity to effectively overcome graft failure after myeloablative HSCT in children.


Preparation of cell envelopes of large numbers of individual bacterial strains with the use of an automatic cell disruptor.
Analysis of the cell envelopes of large numbers of bacterial strains is used for the epidemiological and taxonomic investigation of clinical, veterinarian, and ecological isolates. Isolation of cell envelopes requires lysis of the bacteria. We developed an apparatus to disrupt bacterial cells of 200 different isolates in suspension by ultrasonication automatically. It is composed of modified standard laboratory equipment (fraction collector, cooling unit, pump), a standard ultrasonifier, and a newly designed control unit, which includes a sampler. This apparatus was applied to the analysis of cell envelope proteins of 96 Haemophilus influenzae strains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis within 3 days after the first culture.


Cloning and characterization of two novel genes, cry24B and s1orf2, from a mosquitocidal strain of Bacillus thuringiensis serovar sotto.
Two new crystal protein genes, cry24B and s1orf2, were cloned from a mosquitocidal Bacillus thuringiensis serovar sotto strain. The cry24B and s1orf2 genes encoded a 76-kDa and 62-kDa protein, respectively. The Cry24B protein retained five conserved regions commonly found in the existing Cry proteins. The amino acid sequence of the S1ORF2 had a high homology to that of the ORF2 protein of B. thuringiensis serovar jegathesan. Southern hybridization experiments with a cry24B gene-specific probe revealed that these genes are located on two large plasmids of > 100 kb. When the two genes, cry24B and s1orf2, were expressed in an acrystalliferous B. thuringiensis host, the proteins were synthesized and accumulated as inclusions. These inclusions exhibited no larvicidal activities against three mosquito species: Aedes aegypti, Anopheles stephensi, and Culex pipiens molestus. Likewise, the inclusions contained no cytocidal activity against HeLa cells.


Radiation sensitivity of human carcinoma cells transfected with small interfering RNA targeted against cyclooxygenase-2.
Cyclooxygenase-2 (COX-2) is considered a potential target for cancer therapy, because COX-2 levels are elevated in the majority of human tumors compared with the normal tissues. COX-2 inhibitors inhibit tumor growth and enhance radiation response in vitro as well as in vivo. However, the precise role of COX-2 in radiation response is not clear. The purpose of the present study was to investigate the in vitro radiosensitivity of tumor cells as a function of COX-2 expression. PC3 and HeLa cells express COX-2 protein constitutively. We silenced the COX-2 gene in these cells using small interfering RNA (siRNA). Transfection of PC3 cells with 100 nmol/L siRNA targeted against COX-2 resulted in reduction of COX-2 protein by 75% and inhibition of arachidonic acid-induced prostaglandin E2 synthesis by approximately 50% compared with the vehicle control. In HeLa cells, 100 nmol/L COX-2 siRNA inhibited COX-2 protein expression by 80%. Cell cycle analysis showed that transfection with COX-2 siRNA did not alter the cell cycle distribution. Radiosensitivity was determined by clonogenic cell survival assay. There was no significant difference in the radiosensitivity of cells in which COX-2 was silenced compared with the cells transfected vehicle or with negative control siRNAs (enhancement ratio = 1.1). These data indicate that the in vitro radiosensitivity of tumor cells is minimally dependent on the cellular COX-2 status. Given that a number of potential mechanisms are attributed to COX-2 inhibitors for radiosensitization, specific intervention of COX-2 by RNA interference could help elucidate the precise role of COX-2 in cancer therapy and to optimize strategies for COX-2 inhibition.


Lower Interfacial Resistance between a Ta-Doped Li7La3Zr2O12 (LLZTO) Solid Electrolyte and NiCl2 Cathode by a Simple Heat Treatment for a High-Specific Energy Thermal Battery.
Large current discharge is restricted because of the poor conductivity between the Ta-doped Li7La3Zr2O12 (LLZTO) solid electrolyte and electrode. The poor conductivity would be caused by the interfacial reaction between LLZTO and the cathode, which is detrimental to the secondary Li ionic or metal battery. In this case, we studied the interfacial reaction between LLZTO and a haloid cathode (NiCl2) for a thermal battery for the first time, and a lower interfacial resistance could be obtained by a simple heat treatment. Owing to the element interdiffusion of Cl- and O2- at a high temperature of 600 °C, the main reaction products are LaOCl, LiCl, and La2Zr2O7. This reaction reduces the interfacial resistance from 3 Ω to 2 Ω. After a pretreatment at 600 °C, the discharge specific energy could reach 1254 Wh kg-1 from 828 Wh kg-1 at 550 °C with a cut-off voltage of 1.8 V. These results suggest that the interfacial reaction could be significant for the battery by adding interfacial contact. It is an effective approach to decrease the interfacial resistance at high temperature for some specific system, such as a haloid cathode-solid electrolyte.


Dynamic cross-regulation of antigen-specific effector and regulatory T cell subpopulations and microglia in brain autoimmunity.
Multiple Sclerosis (MS) is considered a T-cell-mediated autoimmune disease with a prototypical oscillatory behavior, as evidenced by the presence of clinical relapses. Understanding the dynamics of immune cells governing the course of MS, therefore, has many implications for immunotherapy. Here, we used flow cytometry to analyze the time-dependent behavior of antigen-specific effector (T(eff)) and regulatory (T(reg)) T cells and microglia in mice model of MS, Experimental Autoimmune Encephalomyelitis (EAE), and compared the observations with a mathematical cross-regulation model of T-cell dynamics in autoimmune disease. We found that T(eff) and T(reg) cells specific to myelin olygodendrocyte glycoprotein (MOG) developed coupled oscillatory dynamics with a 4- to 5-day period and decreasing amplitude that was always higher for the T(eff) populations, in agreement with the mathematical model. Microglia activation followed the oscillations of MOG-specific T(eff) cells in the secondary lymphoid organs, but they were activated before MOG-specific T-cell peaks in the CNS. Finally, we assessed the role of B-cell depletion induced by anti-CD20 therapy in the dynamics of T cells in an EAE model with more severe disease after therapy. We observed that B-cell depletion decreases T(eff) expansion, although its oscillatory behavior persists. However, the effect of B cell depletion was more significant in the T(reg) population within the CNS, which matched with activation of microglia and worsening of the disease. Mathematical modeling of T-cell cross-regulation after anti-CD20 therapy suggests that B-cell depletion may influence the dynamics of T cells by fine-tuning their activation. The oscillatory dynamics of T-cells have an intrinsic origin in the physiological regulation of the adaptive immune response, which influences both disease phenotype and response to immunotherapy.


The organization of dorsal medullary projections to the central amygdaloid nucleus and parabrachial nuclei in the rabbit.
The amygdaloid central nucleus and the pontine parabrachial nucleus receive direct, ascending projections from autonomic regulatory nuclei of the dorsal medulla and are recognized as important components of a forebrain system which contributes to autonomic regulation. The present study was designed to provide more detailed information on the anatomical organization of this ascending system in the rabbit by determining (a) the extent to which separate populations of neurons within the solitary complex project to the central nucleus and parabrachial nucleus, (b) the topographical distribution of the projections of the solitary complex within the amygdaloid central nucleus and parabrachial nucleus and (c) the extent to which projections from the solitary complex to the parabrachial nucleus terminate in the region of origin of projections from the parabrachial nucleus to the amygdaloid central nucleus. A fluorescent dye, double retrograde-labeling technique demonstrated that separate populations of neurons in the solitary complex projected to the amygdaloid central nucleus and parabrachial nucleus. Neurons of both populations were more heavily concentrated within the caudal two thirds of nucleus of the solitary tract and were most numerous within the commissural, medial and dorsomedial subnuclei. Labeled neurons were also located within the dorsal motor nucleus of the vagus nerve. Autoradiographic experiments demonstrated that injections of amino acids into the solitary complex resulted in terminal labeling in the central nucleus. This labeling extended rostrally into the adjacent sublenticular substantia innominata and lateral component of the bed nucleus of the stria terminalis. Label was also observed within the lateral, medial, and Kolliker-Fuse regions of the parabrachial nucleus. A particularly dense field was observed overlying cells located within the ventrolateral region of the lateral parabrachial nucleus. This region contained the majority of labeled neurons within the parabrachial nucleus following fluorescent dye injections into the central nucleus. Furthermore, injections of amino acids into this region resulted in terminal labeling within the central nucleus, with a particularly dense area observed within the medial aspect of the nucleus. The results demonstrate that separate populations of neurons within the solitary complex of the rabbit project to the central amygdaloid and parabrachial nuclei and that the majority of these are located within the caudal two-thirds of the complex.(ABSTRACT TRUNCATED AT 400 WORDS)


Containment wells to form hydraulic barriers along site boundaries.
In the field, aquifer remediation methods include pump and treat procedures based on hydraulic control systems. They are used to reduce the level of residual contamination present in the soil and soil pores of aquifers. Often, physical barriers are erected along the boundaries of the target (aquifer) site to reduce the leakage of the released soil contaminant to the surrounding regions. Physical barriers are expensive to build and dismantle. Alternatively, based on simple hydraulic principles, containment wells or image wells injecting clear water can be designed and built to provide hydraulic barriers along the contaminated site boundaries. For brevity, only one pattern of containment well system that is very effective is presented in detail. The study briefly reports about the method of erecting a hydraulic barrier around a contaminated region based on the simple hydraulic principle of images. During the clean-up period, hydraulic barriers can considerably reduce the leakage of the released contaminant from the target site to surrounding pristine regions. Containment wells facilitate the formation of hydraulic barriers. Hence, they control the movement of contaminants away from the site that is being remedied. However, these wells come into play, only when the pumping operation for cleaning up the site is active. After operation, they can be filled with soil to permit the natural ground water movement. They can also be used as monitoring wells.


The RAGE Gly82Ser polymorphism is not associated with cardiovascular disease in the Framingham offspring study.
The receptor for advanced glycation end-products (RAGE) is expressed to enhance degrees in human atherosclerotic plaques and co-localizes with inflammatory and pro-oxidant mediators in the vulnerable regions of the plaque. Previous studies highlighted a number of variants in the gene encoding the receptor, including a Gly to Ser substitution at amino acid 82 within the ligand-binding domain of RAGE. The Ser82 allele enhanced ligand-binding affinity and increased ligand-stimulated generation of inflammatory mediators in transfected cells and human monocytes compared to the common RAGE Gly82 allele. Thus it was logical to test the hypothesis that increased prevalence of the Gly82Ser polymorphism was associated with cardiovascular events in the Framingham offspring study (n=1632). Our analyses revealed that the Gly82Ser RAGE polymorphism did not demonstrate any association with the incidence of cardiovascular disease in diabetic or non-diabetic subjects (Gly82 96%, Ser82 4%). Analysis of specific manifestations of cardiovascular disease, including coronary heart disease (CHD), cardiovascular disease (CVD), myocardial infarction (MI) and ischemic disease (ISD) revealed no association with RAGE genotype. Further studies are required on other more prevalent genetic variants of RAGE and cardiovascular disease.


Routine induction of labour with extra-amniotic prostaglandin E2 in a viscous gel.
Prostaglandin E2, 350 microgram dispersed in a viscous gel, tylose, was introduced into the extra-amniotic space as a single dose in 285 patients to induce labour. With a favourable cervix, 82 per cent of multiparae and 50 per cent of primiparae were successfully induced. With unfavourable induction features, the success rates were 48 per cent and 24 per cent respectively. In the remaining patients, all but four were successfully delivered when intravenous oxytocin was also used. The method was safe, simple and inexpensive and had many advantages for patients and nursing staff.


Hippo signaling does it again: arbitrating cardiac fibroblast identity and activation.
The Hippo pathway is an evolutionarily conserved kinase cascade that is fundamental for tissue development, homeostasis, and regeneration. In the developing mammalian heart, Hippo signaling regulates cardiomyocyte numbers and organ size. While cardiomyocytes in the adult heart are largely postmitotic, Hippo deficiency can increase proliferation of these cells and affect cardiac regenerative capacity. Recent studies have also shown that resident cardiac fibroblasts play a critical role in disease responsiveness and healing, and in this issue of Genes and Development, Xiao and colleagues (pp. 1491-1505) demonstrate that Hippo signaling also integrates the activity of fibroblasts in the heart. They show that Hippo signaling normally maintains the cardiac fibroblast in a resting state and, conversely, its inactivation during disease-related stress results in a spontaneous transition toward a myofibroblast state that underlies fibrosis and ventricular remodeling. This phenotypic switch is associated with increased cytokine signaling that promotes nonautonomous resident fibroblast and myeloid cell activation.


F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy.
Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989 ± 111 s in the vehicle group to 79 ± 59 s with F 16915, P < 0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P < 0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6 ± 7.4 %, n = 9 vs 17.6 ± 3.4 %, n = 9 in the vehicle group, P < 0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.


Surgical treatment of a presacral schwannoma: A case report.
Schwannomas are rare benign tumors that develop from Schwann cells that represent 0.3 to 0.4 cases per 100,000 persons per year. We report a case of pre-sacral schwannoma, a rare tumor, especially in the pelvic area. This case comes to help further teams in their management as its scarcity made any attempt to make proper recommendations obsolete. a 53-year-old otherwise healthy woman who presented with a 2-year history of right-sided sciatica. The radiologic characteristics of the mass suggested presacral schwannoma type III of the Klimo classification as the most possible diagnosis.Therefore, surgical resection was decided, and an anterior approach was chosen. By laparotomy a 6cm retroperitoneal encapsulated mass with no invasion of the adjacent organs. We performed a digital enucleation of the tumor through a capsulotomy.Pathology confirmed the diagnosis of schwannoma. There were no features of malignancy. The post-operative period was uneventful. A follow-up examination at 6 months showed no signs of numbness or weakness in the right leg. The previously described pain totally regressed. Although schwannoma is a benign lesion, it may become malignant, especially when associated with neurofibromatosis making its surgical removal primordial. Its pelvic location may make its diagnosis delayed due to non-specific symptoms mainly through compression of local organs. Its surgical management can be challenging due to large size tumors with adherence to peritoneal and retroperitoneal organs. Quality of the resection is important in the recurrence and necessity for reoperation. A multidisciplinary approach is therefore recommended to ensure optimal treatment. Due to its rareness, there is no clear consensus in on the management of schwannomas therefore we chose to write our case in order to further enrich the literature to achieve one-day guidelines for schwannoma treatment.


Neurotensin and its amide analogue [Gln4]-neurotensin: effects on brain monoamine turnover.
Intracerebroventricularly administered neurotensin and [Gln4]-neurotensin (50-200 microgram) increased the formation of Dopa in different brain regions of rats after inhibition of the aromatic L-amino acid decarboxylase. For both neuropeptides these increases were dose dependent (20-150%). In the corpus striatum [Gln4]-neurotensin was twice as active as neurotensin and it tended to be more active also in other brain regions. The brain tyrosine concentrations were also increased. [Gln4]-neurotensin (100-200 microgram) following inhibition of the aromatic L-amino acid decarboxylase, increased the accumulation of 5-hydroxytryptophan in all brain regions by 30-60%. In contrast, neurotensin was completely inactive. In both cases the brain tryptophan concentrations were increased. Both neurotensin and [Gln4]-neurotensin also accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. These results show an increased brain monoamine turnover induced by both neuropeptides.


Development of cortical folds in the human brain: An attempt to review biological hypotheses, early neuroimaging investigations and functional correlates.
The folding of the human brain mostly takes place in utero, making it challenging to study. After a few pioneer studies looking into it in post-mortem foetal specimen, modern approaches based on neuroimaging have allowed the community to investigate the folding process in vivo, its normal progression, its early disturbances, and its relationship to later functional outcomes. In this review article, we aimed to first give an overview of the current hypotheses on the mechanisms governing cortical folding. After describing the methodological difficulties raised by its study in fetuses, neonates and infants with magnetic resonance imaging (MRI), we reported our current understanding of sulcal pattern emergence in the developing brain. We then highlighted the functional relevance of early sulcal development, through recent insights about hemispheric asymmetries and early factors influencing this dynamic such as prematurity. Finally, we outlined how longitudinal studies have started to relate early folding markers and the child's sensorimotor and cognitive outcome. Through this review, we hope to raise awareness on the potential of studying early sulcal patterns both from a fundamental and clinical perspective, as a window into early neurodevelopment and plasticity in relation to growth in utero and postnatal environment of the child.


Terminally differentiated human intestinal B cells. J chain expression of IgA and IgG subclass-producing immunocytes in the distal ileum compared with mesenteric and peripheral lymph nodes.
Two-colour immunofluorescence staining for intracellular J chain and IgA (or J chain and IgG) was performed on tissue sections of normal human ileal mucosa (eight adult kidney donors), mesenteric lymph nodes (MLN), peripheral lymph nodes, and palatine tonsils. The most prominent J chain positivity was seen for IgA (97.3%) and IgG (81.7%) immunocytes in the ileal lamina propria (LP). Moreover, the proportion of J chain-expressing extrafollicular immunocytes was significantly higher (P less than 0.05) in MLN than in peripheral lymph nodes for the IgA class (58.5% versus 25.6%); the same proportion for the IgG class was 45.9% versus 30.4%. In clinically normal palatine tonsils of adults, extrafollicular J chain expression was much lower than in peripheral lymph nodes; 14.2% for IgA cells and 5.5% for IgG cells. When related to subclass production, J chain expression was found to be higher for IgA2 than for IgA1 cells in all tissues examined (palatine tonsils excluded because of a small number of IgA2 cells), the difference being significant in MLN and ileal LP (P less than 0.05). The J chain positivity tended to be higher for all IgG subclasses in MLN than in peripheral lymph nodes; this difference was significant (P less than 0.05) for IgG2-producing immunocytes. Taking J chain expression as a marker of clonal immaturity, our results may reflect to some extent distribution of newly generated memory B cell clones from gut-associated lymphoid tissue to MLN, peripheral lymph nodes, and palatine tonsils in a strikingly decreasing order.


Correlations of blood lipids and lipoproteins with coronary artery disease documented by angiography.
A study of the relationships between serum TC, TG and HDL.C and selective coronary arteriography was carried out on 117 patients who were divided into groups according to the extent of artery stenosis. Normal control group consisted of 153 healthy subjects. There were no statistical differences in TC, TG, HDL.C, LDL.C, TC/HDL.C, LDL.C/HDL.C and TC-HDL.C/HDL.C between normal control group and the group with normal coronary arteriogram. LDL.C, TC/HDL.C, LDL.C/HDL.C, TC HDL.C/HDL.C rose and HDL.C decreased as the degree of coronary artery stenosis and the extent of stenosis increased, besides the medium and severe stenosis group. Analyses based on the correlation coefficients indicate that 3 compound indexes (TC-HDL.C/HDL.C, TC-HDL.C, LDL.C/HDL.C) are better in assessing CAD than single index such as LDL.C, HDL.C and TC. The results of our study showed that the 3 compound indexes might be regarded as important risk factors for CAD.


A comparison of odor perception in smokers, nonsmokers, and passive smokers.
The olfactory perception in matched groups of 26 smokers, 26 nonsmokers, and 15 passive smokers was examined psychophysically with two substances, n-butane and pyridine. Different psychophysical functions were obtained from these groups using the method of magnitude estimation. The smokers and passive smokers perceived all concentrations of n-butane to be weaker than did the nonsmokers. In the case of pyridine, a substance in tobacco smoke to which smokers are more exposed, there is an indication of a perceptual deficit similar to loudness recruitment. There were no appreciable differences between smokers and nonsmokers for high concentrations; the sensitivity was less and the psychophysical functions steeper for smokers than nonsmokers for relatively low concentrations. The results are evaluated in terms of information about the subjects' response criteria, and the authors consider the possibility of sensory deficit versus habituation.


Clinical presentation and outcomes of cholecystectomy for acute cholecystitis in patients with diabetes - A matched pair analysis. A pilot study.
The primary aim of this study is to compare the clinical course and laboratory parameters of acute cholecystitis in patients with diabetes vs. patients without diabetes. The study involved patients who underwent emergency cholecystectomy in the Department of General, Endocrine and Transplant Surgery of University Clinical Center in Gdansk (Poland) between 2007 and 2017. There were 267 patients included in the study. The control group of 197 patients was age and sex matched at a 3:1 ratio. The following was compared between the groups: symptoms at admission, course of surgery, postoperative course, length of hospitalization, total costs of hospitalization and antibiotic therapy, other than routine perioperative prophylaxis. There was no significant difference between the patients with and without diabetes regarding symptoms at admission. Operative and postoperative complication rates were significantly higher in the patients with diabetes. The operative time and length of hospitalization were significantly longer in the study group. The conversion rate was not higher in the study group, but classic surgery was performed significantly more often. The patients without diabetes had less pronounced symptoms with more locally advanced disease. Our study demonstrates that patients with diabetes have a significantly more eventful course of acute cholecystitis than patients without diabetes. Patients with diabetes should therefore be qualified for cholecystectomy early in the course of acute cholecystitis.


The effect of U-74389G on liver recovery after acute liver ischemia-reperfusion injury in a swine model.
The potential of U-74389G in attenuating liver damage after ischemia and reperfusion of the liver was studied in a swine model. Eighteen pigs, weighting 28-35 kg, were used in the study. The animals were divided into the following three experimental groups: Group A (control group): Ischemia time 30 min and reperfusion for 120 min (with tissue and blood sampling at both 60 min (A-60) and 120 min (A-120)); Group B: Ischemia time 30 min, U-74389G intraportal injection, and reperfusion for 60 min; and Group C: Ischemia time 30 min, U-74389G intraportal injection, and reperfusion for 120 min. The dose of U-74389G administered was 10 mg/kg animal body weight. Anesthesia was induced with propofol, pancuronium, and fentanyl. Surgery was performed through a midline laparotomy. The portal vein and the common hepatic artery were isolated and prepared for occlusion. Histopathological evaluation revealed a statistically significant difference in portal infiltration in the liver tissue between control group A-60 and group B (P = 0.01), and between control group A-120 and group C (P = 0.002). Hemodynamic and metabolic data in the control and therapy groups at 0, 30, 60, and 120 min were not statistically significantly different. Tissue malondialdehyde levels were statistically significantly different. Tumor necrosis factor-alpha values were statistically significantly different between groups A-60 and B but not between groups A-120 and C. Based on the histological data and the reduction of the malondialdehyde and tumor necrosis factor-alpha levels, administration of U-74389G in ischemia-reperfusion injury of the liver in a swine model has potential in attenuating liver damage.


[Various kinetic properties of beta-glucosidase cloned from Clostridium thermocellum in E. coli].
The kinetics of pNPG, pNPX and cellobiose hydrolysis by beta-glucosidase cloned from C. thermocellum into E. coli was studied. The V values for these substrate hydrolysis are 102, 357 and 6.7 mumols/min/mg protein, respectively; Km are 0.44 mM, 50 mM and 100 mM, respectively, sigma-Gluconolactone inhibits the hydrolysis of all substrates according to a competitive mechanism with Ki of 0.032 mM, 6.0 mM and 0.25 mM, respectively. Glucose inhibits the hydrolysis of pNPG and pNPX also via a competitive mechanism with Ki of 10 mM and 37 mM, while cellobiose--via a mixed type mechanism with Ki of 110 mM and 350 mM. The existence of separate adsorption sites for each substrate and of a common catalytic site for pNPG and pNPX hydrolysis is supposed.


Hyphaema due to blunt trauma.
To study the causes, clinical presentation, complications and visual outcome of hyphaema following closed globe injury. Prospective study. The study was conducted at the Department of Ophthalmology, Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, Pakistan, from May, 1996 to June 1997. All cases of hyphaema, due to closed globe injury, were included and history of patients was recorded on a comprehensive proforma designed for this purpose. All cases were admitted for at least 5 days. Ocular examination included checking visual acuity (VA), intraocular pressure (IOP), slit lamp and fundus examination. Patients were treated accordingly and followed up for 90 days. Thirty-six eyes of 36 patients with hyphaema were included in our study. Out of this, 88.89% were males and 11.11% females while 86% were 20 years of age or below. Almost 91.66% presented with primary hyphaema, 44.44% received trauma with stone and 27.77% with tennis ball while playing cricket. Trauma during playing was noted in 66.66% of cases. Almost 62% of cases were having visual acuity in the range of CF to perception of light with good projection. IOP was raised initially in 41.66% cases. Only 33.33% needed surgical intervention. Secondary glaucoma was present in 13.88% and 5.55% had corneal blood staining. Majority of patients (75%) improved to VA range of 6/6 to 6/12 and 19% patients in our study ended up with legal blindness in the affected eyes. Traumatic hyphaema is more frequently found among children and young male. Angle recession, traumatic cataract and maculopathy were common co-morbidities. Secondary glaucoma and corneal staining were the main complications. Nearly 1/5th of patients ended up with legal blindness in the affected eyes.


Selective nucleation and growth of metal-organic open framework thin films on patterned COOH/CF3-terminated self-assembled monolayers on Au(111).
Metal-Organic open Framework coordination polymers (MOFs) are a fascinating class of materials. We demonstrate the selective growth of patterned thin films of MOF-5 and the subsequent loading with a palladium organic compound, which acts as a precursor for the deposition of palladium nanoclusters inside the cavities of the MOF-5 material.


[Spontaneous renal subcapsular or perinephric haematoma].
To improve the diagnosis and treatment of spontaneous renal subcapsular and perinephric haematoma. Seventeen cases of spontaneous renal subcapsular or perinephric haematoma were analyzed retrospectively. For imaging diagnosis, we used ultrasonography, computerized tomography (CT) and angiography. Thirteen cases were subjected to nephrectomy and one case was to renal biopsy, whereas the remaining 3 cases were treated conservatively. After follow up for 6-108 months, 3 patients died and 14 patients survived. For diagnosis, imaging examinations are very valuable. For treatment, most of patients with perinephric haematoma should be operated on.


Position-Scanning Peptide Libraries as Particle Immunogens for Improving CD8+ T-Cell Responses.
Short peptides reflecting major histocompatibility complex (MHC) class I (MHC-I) epitopes frequently lack sufficient immunogenicity to induce robust antigen (Ag)-specific CD8+ T cell responses. In the current work, it is demonstrated that position-scanning peptide libraries themselves can serve as improved immunogens, inducing Ag-specific CD8+ T cells with greater frequency and function than the wild-type epitope. The approach involves displaying the entire position-scanning library onto immunogenic nanoliposomes. Each library contains the MHC-I epitope with a single randomized position. When a recently identified MHC-I epitope in the glycoprotein gp70 envelope protein of murine leukemia virus (MuLV) is assessed, only one of the eight positional libraries tested, randomized at amino acid position 5 (Pos5), shows enhanced induction of Ag-specific CD8+ T cells. A second MHC-I epitope from gp70 is assessed in the same manner and shows, in contrast, multiple positional libraries (Pos1, Pos3, Pos5, and Pos8) as well as the library mixture give rise to enhanced CD8+ T cell responses. The library mixture Pos1-3-5-8 induces a more diverse epitope-specific T-cell repertoire with superior antitumor efficacy compared to an established single mutation mimotope (AH1-A5). These data show that positional peptide libraries can serve as immunogens for improving CD8+ T-cell responses against endogenously expressed MHC-I epitopes.


Electrochemical immunosensor for carcinoembryonic antigen based on nanosilver-coated magnetic beads and gold-graphene nanolabels.
A novel redox-active magnetic nanostructure was synthesized by using a wet chemical method for high-efficiency electrochemical immunoassay of carcinoembryonic antigen (CEA, as a model analyte). The nanostructures based on the combination of a magnetic nanocore, a layer of electroactive poly(o-phenylenediamine) (PPD), and a silver metallic shell displayed good adsorption properties for the attachment of anti-CEA antibody selective to CEA. The magnetic nanostructure presented good redox behaviors to facilitate and modulate the way it was integrated into a magnetic carbon paste electrode. The assay was based on a sandwich-type immunoassay protocol by using nanogold-patterned graphene oxide nanoscales (AuNP-GO), conjugated with horseradish peroxidase-labeled anti-CEA, as secondary antibodies and biofunctionalized magnetic nanostructures as immunosensing probes. Under optimal conditions, the nanoparticle-based immunocomposites exhibited good electrochemical responses for the determination of CEA, and allowed the detection of CEA at a concentration as low as 1.0 pg mL(-1) at a signal-to-noise ratio of 3. In addition, the magnetic immunosensing had good reproducibility, and acceptable accuracy, and could be successfully applied for the detection of CEA in the clinical serum specimens. Significantly, by controlling the target biomolecules, this assay can be easily extended for use with other immunosensings, and thus represents a versatile design routine.


[The chordoma. Description of 2 clinical cases and results of oncolytic chemotherapy].
Only seven hundred cases of chordoma approximatively are reported in medical literature from 1850 to date. We now describe two cases recently observed at our Medical Division, one of sacro-coccigeal chordoma and the other developed from clivus of Blumenbach. Their peculiarities are briefly discussed and compared with a rapid revision of the literature on this argument. The results of antiblastic therapy are presented and its opportunity in addition to Roentgenologic and surgical therapy is discussed.


The role of chemotherapy in the treatment of gliomas in adults.
Glioblastomas and previously irradiated recurrent gliomas remain incurable. Chemotherapy is able to palliate patients by shrinking tumors, thereby improving neurological status and quality of life. Chemotherapy may also be capable of prolonging survival in some instances. The effectiveness of chemotherapy against gliomas is comparable to the efficacy of chemotherapy against many other solid tumors. When given in an adjuvant setting along with radiation postoperatively, studies suggest that the nitrosoureas, dibromodulcitol, dianhydrogalactitol, procarbazine, teniposide, dacarbazine, and cisplatin may possibly be useful, although results for many of these drugs are inconclusive. Some chemotherapy combinations also appear to be useful in an adjuvant setting, particularly BCNU plus ifosfamide, BCNU plus cisplatin, CCNU plus dibromodulcitol, and CCNU plus lonidamine. However, there is not yet conclusive evidence that combination chemotherapy is superior to single agent adjuvant chemotherapy in the treatment of gliomas. While the use of chemotherapy prior to postoperative cranial radiation is worthy of further study, it has not to date proven to be more effective than chemotherapy combined with radiation. In patients whose tumors have recurred following radiation, palliation may be achieved with the nitrosoureas, procarbazine, teniposide, and diaziquone. Cisplatin, high dose methotrexate, the interferons, and a variety of other medications also may be of use. As in the case of adjuvant chemotherapy, chemotherapy combinations for recurrent tumor have not been conclusively demonstrated to be superior to single agent treatment, although some CCNU-based combinations are of interest. Many different chemotherapy drugs have been administered by intracarotid infusion. There is a moderately high risk of serious local retinal and neurological toxicity using this approach, and efficacy has not been proven to be improved by this approach. However, further studies of intraarterial administration of chemotherapy are warranted in light of theoretical considerations, pharmacological observations of enhanced local drug concentrations, and the observation that patients who have failed the same drugs intravenously may respond when lower doses of the drug are administered intraarterially. In addition, some patients have had tumor shrinkage in the area infused while tumor has grown in other areas. Thus, while intracarotid chemotherapy must be regarded as still investigational and potentially quite toxic, further studies are indicated. High dose chemotherapy has been administered in combination with autologous bone marrow rescue. High response rates and prolonged survival durations have been reported in some instances, justifying further study despite substantial toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)


Variability of annual sediment load and runoff in the Yellow River for the last 100 years (1919-2018).
The sediment load of the Yellow River, once the highest in the world, has decreased to a record low. The annual sediment load (ASL, t·yr-1) in the main stream of the Yellow River in the past 100 years (1919-2018) shows that the ASL was consistently high for the first 60 years and then decreased gradually until 1999, when the Green for Grain Project (GGP) launched on the Loess Plateau caused ASL to drop sharply. The annual runoff did not decrease as much as ASL from 1919 to 2018, while it decreased significantly in the middle reaches. With the construction of sediment storage dams, terraces, and reservoirs, especially after the GGP launched, the ASL of the Yellow River has been reduced to historic lows. For example, the annual average Normalized Difference Vegetation Index (NDVI) of the Yellow River Basin increased significantly from 1982 to 2016, and the ASL decreased exponentially with increasing NDVI. Although the annual precipitation has a stationary behavior in the Yellow River, the daily precipitation extremes affecting erosion showed an increase of 7% per degree of warming but did not change the trend of ASL reduction. Therefore, the effective management on the Loess Plateau can control the trend of the sediment load of the Yellow River. Erosion, sediment load, and runoff in changing environments are affected by flood control and drought resistance, so more attention should be paid to these hydrologic processes.


Mate guarding and territorial aggression vary with breeding synchrony in golden whistlers (Pachycephala pectoralis).
Male paternity assurance behaviour during the female fertile period has been widely documented amongst birds. In contrast, how sex-specific behavioural strategies vary with local breeding synchrony levels remains largely unknown. This is important because, in many species, intra-population patterns of extra-pair fertilisation rates, and hence cuckoldry risk, are known to vary with the number of simultaneously fertile females. Each sex may therefore differ in how they behave towards male conspecifics during different degrees of breeding synchrony. Here I provide evidence of such sex-specific differences in the golden whistler (Pachycephala pectoralis), a species in which within-pair paternity assurance is negatively associated with breeding synchrony. Via simulated territorial intrusions using decoy males, I show that males, but not females, increase levels of aggression to male intruders during periods of low synchrony, possibly because cuckoldry risk is greatest during this period. In addition, males appear to invest more effort into mate guarding after, but not before, territorial intrusions during this period. These inter-sexual differences may reflect conflicts in interest between the sexes, with females consistently showing interest in males during the fertile period regardless of synchrony levels and males investing more resources into expelling intruders when the risk of paternity loss is greatest. This study thus provides evidence that males may be able to detect variation in breeding synchrony and cuckoldry risk and adjust their paternity assurance behaviour accordingly.


Binding properties of ruthenium(II) complexes [Ru(bpy)2(ppn)](2+) and [Ru(phen)2(ppn)](2+) with triplex RNA: As molecular "light switches" and stabilizers for poly(U)·poly(A)*poly(U) triplex.
Stable RNA triplexes play key roles in many biological processes, while triplexes are thermodynamically less stable than the corresponding duplexes due to the Hoogsteen base pairing. To understand the factors affecting the stabilization of RNA triplexes by octahedral ruthenium(II) complexes, the binding of [Ru(bpy)2(ppn)](2+) (1, bpy=2,2'-bipyridine, ppn=2,4-diaminopyrimido[5,6-b]dipyrido[2,3-f:2',3'-h]quinoxaline) and [Ru(phen)2(ppn)](2+) (2, phen=1,10-phenanthroline) to poly(U)·poly(A)*poly(U) (· denotes the Watson-Crick base pairing and * denotes the Hoogsteen base pairing) has been investigated. The main results obtained here suggest that complexes 1 and 2 can serve as molecular "light switches" and stabilizers for poly(U)·poly(A)*poly(U), while the effectiveness of complex 2 are more marked, suggesting that the hydrophobicity of ancillary ligands has a significant effect on the two Ru(II) complexes binding to poly(U)·poly(A)*poly(U). This study further advances our knowledge on the binding of RNA triplexes with metal complexes, particularly with octahedral ruthenium polypyridyl complexes.


Chronic catatonia treated with electroconvulsive therapy: a case report.
In the International Statistical Classification of Diseases and Related Health Problems 10 and Diagnostic and Statistical Manual of Mental Disorders IV classification systems, catatonia is classified as a subtype of schizophrenia. However, catatonia is more frequently associated with mood disorders than schizophrenia. It is also associated with organic conditions. Catatonia responds to treatment with benzodiazepines and electroconvulsive therapy rather than antipsychotics. These features support the categorization of catatonia as an independent syndrome. There is a lack of consensus regarding the definition of chronic catatonia. There are two previous case reports of effective treatment of chronic catatonia with electroconvulsive therapy. A 29-year-old South Asian woman was admitted to hospital because of poor food intake. Her condition had progressively worsened over the past seven months. She had features of catatonia. On admission, her Bush-Francis Catatonia Rating Scale score was 24. Her symptoms resolved after the administration of 17 electroconvulsive therapies but recurred later. She was given a further four electroconvulsive therapies. She remains well on aripiprazole at a dose of 60mg a day. Bilateral electroconvulsive therapy is effective in the treatment of chronic catatonia and should be considered as a treatment option. A relapse of symptoms can occur after the discontinuation of treatment.


To explore the association of Ramadan fasting with symptoms of depression, anxiety, and stress in people with diabetes.
To explore the association of Ramadan fasting with symptoms of depression, anxiety, and stress in people with diabetes. This observational study was conducted at Baqai Institute of Diabetology and Endocrinology between May-July 2017. Informed consent was taken from each study participant. Demographic and baseline data was recorded. DASS-21 scale was used to assess symptoms of depression, anxiety, and stress pre and post Ramadan. A total of one hundred and fifty people with diabetes participated in this study. 100 people were in fasting group and 50 were in non-fasting group. In fasting group pre-Ramadan depression, anxiety and stress symptoms were present in 45%, 45%,49% of people which improved to 23%, 26%, 35% post Ramadan (p-value <0.0001, <0.0001, 0.001) respectively. In non-fasting group pre-Ramadan depression and anxiety symptoms were present in 34%, and 50% of people, which improved to 30% and 40% post Ramadan (p-value 0.625, 0.227) respectively, while no improvement was observed in stress symptoms. There is significant improvement in symptoms of depression, anxiety, and stress in people with diabetes post-Ramadan fasting.


Food Choice Questionnaire (FCQ) revisited. Suggestions for the development of an enhanced general food motivation model.
Recognising the need for a more statistically robust instrument to investigate general food selection determinants, the research validates and confirms Food Choice Questionnaire (FCQ's) factorial design, develops ad hoc a more robust FCQ version and tests its ability to discriminate between consumer segments in terms of the importance they assign to the FCQ motivational factors. The original FCQ appears to represent a comprehensive and reliable research instrument. However, the empirical data do not support the robustness of its 9-factorial design. On the other hand, segmentation results at the subpopulation level based on the enhanced FCQ version bring about an optimistic message for the FCQ's ability to predict food selection behaviour. The paper concludes that some of the basic components of the original FCQ can be used as a basis for a new general food motivation typology. The development of such a new instrument, with fewer, of higher abstraction FCQ-based dimensions and fewer items per dimension, is a right step forward; yet such a step should be theory-driven, while a rigorous statistical testing across and within population would be necessary.


Use of a Dual-Filter Embolic Protection Device for Brachiocephalic Artery Stenting.
A 77-year-old female with peripheral artery disease underwent brachiocephalic artery stenting for right upper extremity claudication. Given a very high atherosclerotic burden seen on CT, a dual-filter embolic protection device (Sentinel, Boston Scientific) was deployed from the right radial artery to protect the right common carotid and subclavian arteries, and therefore the vertebral artery, during the stenting procedure. This case report demonstrates a novel use of this dual-filter device to provide both carotid and vertebral artery embolic protection during brachiocephalic artery intervention.


Treatment outcome in orthognathic surgery - A prospective comparison of accuracy in computer assisted two and three-dimensional prediction techniques.
The main objective of the present study was to assess the accuracy of two- and three-dimensional prediction techniques in orthognathic surgery. It was also a test of the very planning sequence. The scientific question was how well does the software support the surgeon in his way to find the perfect correction of the facial appearance while normalizing the occlusion? Thirty patients with a class III occlusion were included in this prospective study. Surgical planning with both techniques were undertaken for all patients. Surgery was performed according to the two-dimensional technique. The cephalometric measurements from two-dimensional and three dimensional predictions were compared with the postoperative results at the 12 months follow-up respectively. Together with an analysis of tracing error, placements of 2020 markers, 1860 measurements and 1280 comparisons was performed. The analysis showed an equally high accuracy for the studied techniques. The highest accuracy was found in the anterior maxilla. There was a tendency for an overestimation for the three-dimensional technique and an underestimation for the two-dimensional technique. CONCLUSIONS: The present study indicates an equal high accuracy in predicting facial outcome for both studied techniques. However, in those patients with asymmetric malocclusion and/or facial appearance the three-dimensional technique has an obvious advantage.


Total Hip Arthroplasty is the Most Effective Treatment for Atraumatic Subchondral Insufficiency Fractures of the Femoral Head.
Subchondral insufficiency fracture of the femoral head (SIFH) is a relatively newly used diagnosisfollowing an insidious onset of hip pain in individuals without apparent antecedent trauma. The aim of this study was to investigate the outcomes of a consecutive series of patients with SIFH treated at one institution. A total of 93 patients aged 23 to 91 years who were treated for SIFH in the outpatient clinics at one academic, urban medical center between August 2012 and August 2019 were identified. The diagnosis was made by magnetic resonance imaging or radiograph of the hip and was confirmed by a radiologist specialized in orthopedic surgery. Patient demographics, injury history, duration of pain, treatment type, and persistence of pain were recorded. Sixty-five (69.9%) patients with a mean age of 64.2 ± 9.4 years ultimately underwent total hip arthroplasty (THA). Twenty-eight (30.1%) patients chose no surgical intervention. Patients who underwent THA had less pain at their final follow-up appointment than patients who elected non-operative treatment (p < 0.001). At their final follow-up appointments, 92.9% of patients treated non-operatively reported pain, compared to only 13.8% of patients who underwent THA who had pain. Age, body mass index, and duration of pain prior to initial complaint did not affect presence of continued pain at final follow-up appointments, regardless of treatment type (p > 0.05). In the majority of patients, SIFH is often not sufficiently managed with non-operative treatments. Pain reported among patients with confirmed or suspected SIFH is usually severe and interferes with patients' ability to perform their activities of daily life. Total hip arthroplasty seems to be the most reliable method of treatment for this condition. Physicians who treat patients with SIFH should counsel them as to the expectations of recovery and the potential for poorer outcome if treated without THA.


LncRNA ROR1‑AS1 high expression and its prognostic significance in liver cancer.
Hepatocellular carcinoma (HCC) is a common disease of the digestive system with no curative treatments. Long noncoding RNA tyrosine protein kinase transmembrane receptor 1 antisense RNA 1 (lncRNA ROR1‑AS1) is an lncRNA whose functions have been predicted in human diseases; however, its important role in cancer has been probed only in mantle cell lymphoma, not in HCC. Therefore, the present study aimed to elucidate the prognostic significance of lncRNA ROR1‑AS1 in HCC. The Cancer Genome Atlas Liver Hepatocellular Carcinoma was used to analyze the expression of ROR1‑AS1 in liver cancer. χ2 tests were performed to evaluate associations between clinical characteristics and ROR1‑AS1 expression. The role of ROR1‑AS1 in HCC prognosis was assessed using Kaplan‑Meier curves and proportional hazards model (Cox) analysis. Gene set enrichment analysis was performed by using a Gene Expression Omnibus dataset. At the same time, Multi Experiment Matrix was used to predict genes that may be co‑expressed with ROR1‑AS1. The Database for Annotation, Visualization and Integrated Discovery and KO‑Based Annotation System were used to analyze the most closely associated cytological behaviors and pathways in HCC. Then, the genes in the three databases were integrated to screen mRNAs, microRNAs and lncRNAs that had co‑expression relationships with ROR1‑AS1. Cytoscape, Search Tool for the Retrieval of Interacting Genes/Proteins and Molecular Evolutionary Genetics Analysis were used to map potential regulatory networks and developmental relationships associated with ROR1‑AS1. Finally, 12 genes most closely associated with ROR1‑AS1 were identified, and their relationship was described using a Circos plot. The results showed that ROR1‑AS1 was upregulated in HCC, and its expression was related to clinical stage, T stage and N stage. Furthermore, Kaplan‑Meier curves and Cox analysis indicated that high expression of ROR1‑AS1 was associated with poor prognosis, and that ROR1‑AS1 was an independent risk factor for HCC. Co‑expression data suggested that there may be a large regulatory network of 45 genes with indirect associations with ROR1‑AS1, a small regulatory network of 15 genes with direct or indirect regulatory relationships, and a special regulatory network containing 12 genes directly associated with ROR1‑AS1. The present findings indicated that high expression of ROR1‑AS1 suggests poor prognosis in patients with HCC.


Degradation of trichothecene mycotoxins by aqueous ozone.
The degradation of ten trichothecene mycotoxins by aqueous ozone was monitored by liquid chromatography-ultraviolet-mass spectrometry (LC-UV-MS). Saturated aqueous ozone ( approximately 25 ppm) degraded these mycotoxins to materials that were not detected by UV or MS. At lower levels (approximately 0.25 ppm) of aqueous ozone, intermediate products were observed. On the basis of UV and MS data, it is proposed that the degradation begins with attack of ozone at the C9-10 double bond with the net addition of two atoms of oxygen. The remainder of the molecule appears to have been left unaltered. The oxidation state at the allylic carbon 8 position had a significant effect on the ease of reaction, as determined by moles of ozone required to effect oxidation. The amount of ozone required to effect oxidation to intermediate products and subsequent degradation followed the series allylic methylene (no oxygen) < hydroxyl (or ester) < keto. Ozonation was also sensitive to pH. At pH 4-6, all mycotoxins studied degraded readily; at pH 7-8 the degree of reactivity was dependent upon the carbon 8 oxidation state; at pH 9, there was little or no reaction. Structures for some of the intermediate products are proposed.


Long-term results of variceal bleeding management in 302 patients with chronic extrahepatic portal vein obstruction.
Treatment modalities of variceal bleeding or rebleeding for extrahepatic portal vein obstruction (EHPVO) are limited, and their long-term results and prognostic factors are unclear. This study aimed at assessing the long-term results of EHPVO treated with current recommendations and investigating the influencing factors. Between 2009 and 2016, 302 consecutive patients with EHPVO were included. Watch-and-wait policy was applied for those with no (n = 59) or small varices (n = 55), nonselective beta-adrenergic blocker and nonselective beta-adrenergic blocker plus endotherapy were for primary (n = 115) and secondary prophylaxis (n = 87), transjugular intrahepatic portosystemic shunt (TIPS) or combination therapy was for those with recurrent bleeding (n = 92). The median follow up was 58.8 months. The 1-, 3-, and 5-year cumulative rates were 3.6%, 19.2%, 32.3% for small varices development and 4.5%, 30.9%, 53.4% for large varices development. The 1-, 3-, and 5-year cumulative rates were 11.1%, 20.9%, and 34.9% for first variceal bleeding and 16.0%, 26.9%, and 33.6% for variceal rebleeding. For those with recurrent variceal bleeding, only TIPS (n = 37, technical success rate: 90.2%) was associated with a reduced risk of variceal rebleeding (1-, 3-, and 5-year: 5.6%, 11.7%, and 21.9%). The 1-, 3-, and 5-year survival rates were 96.9%, 95.8%, and 91.9%. Prothrombotic factors and anticoagulation did not influence the risk of variceal bleeding, rebleeding, and survival. By applying the same variceal management as recommended for patients with liver cirrhosis, patients with non-cirrhotic EHPVO showed a similar development of varices and variceal bleeding. This is also true for the beneficial effect of TIPS to prevent rebleeding.


Sequence of neuron origin in experimentally distorted brains of chick embryos.
The effects of proliferative disorders on the time and sequence of neuron origin in the optic tectum were studied in chick embryos in which "overgrowth" had been experimentally induced, Sixteen normal and fourteen abnormal embryos ranging in age from four through ten days of incubation were each given a single dose of thymidine[3H]. Comparisons were then made between 16-day normal and abnormal chick embryos with respect to the distribution tectum midway between its rostral and caudal boundaries. In the normal and abnormal tecta layers I-IV were generated on days 3-6. Differences occurred in the generation of the remaining layers. In the normal embryos layers V-VII arose on days 5-8 and layers VIII-XV on days 4-7; in the abnormal embryos layers V-VII originated on days 6-8 and layers VIII-XV on days 5-8. In addition to the delay in onset of neuron origin, the abnormal tectum also showed distorted lamination, particularly in layers VIII-XV which constitute the superficial regions of the stratum griseum and fibrosum superficiale. Despite the defect in time and sequence of neuron origin, the rostroventrolateral to caudodorsomedial gradient of maturity characteristic of the normal tecta was not disturbed in the abnormal tecta.


Laparoscopic orchiopexy of intraabdominal undescended testis associated with congenital diaphragmatic hernia.
Laparoscopy is an advantageous method for the repair of intraabdominal undescended testis since both an abdominal exploration and vascular elongation can be effectively performed by laparoscopic assistance. A 3-year-old boy and a 1-year-old boy complaining of unilateral nonpalpable left testes were observed following previous congenital diaphragmatic hernia repairs on the day of birth. In these operations, a laparoscopic working sheath was inserted through a small supraumbilical incision. On each boy, a laparoscopically intraabdominal testis was found close to the left internal inguinal ring. In addition, a 10-mm trocar port was placed in the right lower abdominal quadrant and a 5-mm port was placed in the left lower quadrant. For the purpose of orchiopexy, the left testicular vessels were isolated over their full length. The left side of the testis was pulled through the inguinal ring to an inguinal canal divided by the abdominal wall, and then was retracted into the scrotum. The internal ring was thereafter closed externally by the fascia transversalis. Both patients are doing well, with no testicular atrophy or inguinal hernia for 1 and 2 years, respectively, after the above operations.


LDHA mediated degradation of extracellular matrix is a potential target for the treatment of aortic dissection.
Aortic dissection (AD) is a disease with high mortality and lacks effective drug treatment. Recent studies have shown that the development of AD is closely related to glucose metabolism. Lactate dehydrogenase A (LDHA) is a key glycolytic enzyme and plays an important role in cardiovascular disease. However, the role of LDHA in the progression of AD remains to be elucidated. Here, we found that the level of LDHA was significantly elevated in AD patients and the mouse model established by BAPN combined with Ang II. In vitro, the knockdown of LDHA reduced the growth of human aortic vascular smooth muscle cells (HAVSMCs), glucose consumption, and lactate production induced by PDGF-BB. The overexpression of LDHA in HAVSMCs promoted the transformation of HAVSMCs from contractile phenotype to synthetic phenotype, and increased the expression of MMP2/9. Mechanistically, LDHA promoted MMP2/9 expression through the LDHA-NDRG3-ERK1/2-MMP2/9 pathway. In vivo, Oxamate, LDH and lactate inhibitor, reduced the degradation of elastic fibers and collagen deposition, inhibited the phenotypic transformation of HAVSMCs from contractile phenotype to synthetic phenotype, reduced the expression of NDRG3, p-ERK1/2, and MMP2/9, and delayed the progression of AD. To sum up, the increase of LDHA promotes the production of MMP2/9, stimulates the degradation of extracellular matrix (ECM), and promoted the transformation of HAVSMCs from contractile phenotype to synthetic phenotype. Oxamate reduced the progression of AD in mice. LDHA may be a therapeutic target for AD.