[Eye muscle surgery in persistent bilateral trochlear paralysis and concomitant Brown phenomenon after indirect craniocerebral trauma].
Rarely, an additional Brown's syndrome develops spontaneously in cases of posttraumatic bilateral superior oblique palsy. Surgical measures are controversial and problematic. We here report on a 40-year-old patient who, 2 years after blunt head trauma, presented with residual bilateral VIth nerve palsy with 12 degrees excyclotropia in downgaze, abnormal head postures of 20 degrees chin down position in binocular viewing and reduced elevation in adduction. His binocular field of gaze ranged from 10 degrees upgaze to 25 degrees upgaze. After thorough discussion of the situation we suggested bilateral superior oblique tucking, depending on interoperative findings. In a forced duction test under general anesthesia both eyes showed restricted elevation in adduction. Both superior oblique tendons seemed stiff. A 2.5-mm tuck (right) and a 3.0-mm tuck (left) of the anterior part of the tendon were performed. After operation the patient showed a central field of binocular fusion ranging from 10 degrees upgaze to 25 degrees downgaze, in right gaze up to 30 degrees and in left gaze unrestricted. Excyclotropia was present only in downgaze and not more than 6 degrees. A low-dosage anterior tuck of the superior oblique tendon was successful in eliminating excyclotropia sufficiently and enlarging the binocular field of fusion.


Glycine-immunoreactive neurons in the brain of a shark (Scyliorhinus canicula L.).
The glycinergic cell populations in the brain of the lesser spotted dogfish were studied by a glycine immunofluorescence method. Numerous glycine-immunoreactive (Gly-ir) neurons were observed in different brain nuclei. In the telencephalon, Gly-ir cells were observed in the olfactory bulb, telencephalic hemispheres, and preoptic region. In the hypothalamus, cerebrospinal fluid-contacting Gly-ir neurons were observed in the lateral and posterior recess nuclei. Coronet cells of the saccus vasculosus were Gly-ir. In the diencephalon, Gly-ir neurons were observed in the prethalamus and pretectum. In the midbrain, both the optic tectum and lateral mesencephalic nucleus contained numerous Gly-ir neurons. In the cerebellum, many Golgi cells were Gly-ir. In the rhombencephalon, Gly-ir cells were observed in the medial and ventral octavolateral nuclei, vagal lobe, visceromotor nuclei, and reticular formation, including the inferior raphe nucleus. In the spinal cord, some neurons of the marginal nucleus and some cells of the dorsal and ventral horns were Gly-ir. Comparison of dogfish Gly-ir cell populations with those reported for the sea lamprey, Siberian sturgeon, and zebrafish revealed some shared features but also notable differences. For example, Gly-ir cells were observed in the dogfish cerebellum, unlike the case in the Siberian sturgeon and zebrafish, whereas the absence of Gly-ir neurons in the isthmus is shared by all these species, except for lampreys. Gly-ir populations in the dogfish hypothalamus and telencephalon are notable in comparison with those of the other jawed vertebrates investigated to date. Together, these results reveal a complex and divergent evolution of glycinergic systems in the major groups of fishes.


New betaproteobacterial Rhizobium strains able to efficiently nodulate Parapiptadenia rigida (Benth.) Brenan.
Among the leguminous trees native to Uruguay, Parapiptadenia rigida (Angico), a Mimosoideae legume, is one of the most promising species for agroforestry. Like many other legumes, it is able to establish symbiotic associations with rhizobia and belongs to the group known as nitrogen-fixing trees, which are major components of agroforestry systems. Information about rhizobial symbionts for this genus is scarce, and thus, the aim of this work was to identify and characterize rhizobia associated with P. rigida. A collection of Angico-nodulating isolates was obtained, and 47 isolates were selected for genetic studies. According to enterobacterial repetitive intergenic consensus PCR patterns and restriction fragment length polymorphism analysis of their nifH and 16S rRNA genes, the isolates could be grouped into seven genotypes, including the genera Burkholderia, Cupriavidus, and Rhizobium, among which the Burkholderia genotypes were the predominant group. Phylogenetic studies of nifH, nodA, and nodC sequences from the Burkholderia and the Cupriavidus isolates indicated a close relationship of these genes with those from betaproteobacterial rhizobia (beta-rhizobia) rather than from alphaproteobacterial rhizobia (alpha-rhizobia). In addition, nodulation assays with representative isolates showed that while the Cupriavidus isolates were able to effectively nodulate Mimosa pudica, the Burkholderia isolates produced white and ineffective nodules on this host.


Uterine packing in the combined management of obstetrical hemorrhage.
Uterine packing to control obstetrical hemorrhage has been generally discouraged over the past several decades. Intractable uterine hemorrhage postpartum or following an abortion is an extremely vexing management problem for the physician and continues to be a leading cause of maternal mortality. Uterine packing should be considered as a presurgical management tool after lacerations of the lower genital tract, uterine rupture, or retained products have been ruled out and when conventional therapy fails to control uterine hemorrhage. We describe two obstetrical patients with intractable uterine hemorrhage who were managed with uterine packing in combination with other methods of therapy. Causes of obstetrical hemorrhage and techniques of packing the uterus are discussed.


From Wet-Lab to Variations: Concordance and Speed of Bioinformatics Pipelines for Whole Genome and Whole Exome Sequencing.
As whole genome sequencing becomes cheaper and faster, it will progressively substitute targeted next-generation sequencing as standard practice in research and diagnostics. However, computing cost-performance ratio is not advancing at an equivalent rate. Therefore, it is essential to evaluate the robustness of the variant detection process taking into account the computing resources required. We have benchmarked six combinations of state-of-the-art read aligners (BWA-MEM and GEM3) and variant callers (FreeBayes, GATK HaplotypeCaller, SAMtools) on whole genome and whole exome sequencing data from the NA12878 human sample. Results have been compared between them and against the NIST Genome in a Bottle (GIAB) variants reference dataset. We report differences in speed of up to 20 times in some steps of the process and have observed that SNV, and to a lesser extent InDel, detection is highly consistent in 70% of the genome. SNV, and especially InDel, detection is less reliable in 20% of the genome, and almost unfeasible in the remaining 10%. These findings will aid in choosing the appropriate tools bearing in mind objectives, workload, and computing infrastructure available.


Detection of the dominant expression of the TEPC-15 idiotypic determinant(s) on phosphorylcholine-specific suppressor T lymphocytes in vitro.
Phosphorylcholine-(PC) specific suppressor T lymphocytes, induced by immunization with PC-coupled syngeneic spleen cells and capable of suppressing antibody production in an in vitro system, were successfully obtained by removal of a PC-nonspecific, i.e., diazo-phenylstructure-directed, suppressor cell population using an immunoadsorbent column coupling an unrelated hapten with a diazo phenyl structure such as azobenzene arsonate (ABA). Column-purified PC-specific suppressor T cell activity was completely abrogated by treatment of the cells with anti-TEPC-15 (T-15) anti-idiotypic antibody and complement, or by the continuous presence of that antibody in the culture, whereas nonpurified suppressor cell activity was resistant to such treatment. Thus, the column-purified PC-specific suppressor T lymphocytes in BALB/c mice have a very homogeneous T-15 idiotypic determinant(s) on their functional receptors for antigen similar to those present on PC-specific antibody and/or B lymphocytes. Because of these results, we envision the growing importance of analysis of the fine specificity of the idiotype repertoire of T lymphocytes after purification of a hapten-specific population.


Complete mitochondrial genome of javeline goby (Synechogobius hasta).
In this study, we cloned and sequenced the complete mitochondrial DNA (mtDNA) of Synechogobius hasta to characterize and compare their mitochondrial genomes. The total length of the mitochondrial genome is 16,655 bp with an accession number KM891736. The organization of the mitochondrial genomes was similar to those reported from other fish mitochondrial genomes containing 37 genes (13 protein-coding genes, 2 ribosomal RNA and 22 transfer RNAs) and a major non-coding control region. Except for ND6 and 8 tRNAs, all other genes are encoded on the heavy strand. The base composition of the 13 mitochondrial protein-coding genes in the third position was relatively low (9.7%). The complete mitogenome may provide important date set for the study of genetic mechanism of S. hasta.


Quantification of the trabecular bone volume fraction for bone marrow dosimetry in molecular radiotherapy by using a dual-energy (SPECT/)CT.
A complete characterization of spongiosa (bone marrow plus trabecular bone) is required to calculate the absorbed dose to active bone marrow. Due to the complex microanatomy, it is necessary to apply non-conventional imaging methods in nuclear medicine. The aim of this study is validating a phantomless quantification method using dual-energy quantitative computed tomography (DEQCT) for the quantification of trabecular bone volume fraction for bone marrow dosimetry in molecular radiotherapy. First, a phantomless quantification method (mass fraction method) based on x-ray beam and detector sensitivity was validated in an integrated dual energy SPECT/CT and in a dual source computed tomography (DSCT) system for comparison. The validation was performed in a phantom consisting of different water, fat and hydroxyapatite compositions. Moreover, the European spine phantom (ESP) was used to simulate the spine geometry. Bone mineral content (BMC) of the whole vertebra and bone mineral density (BMD) in the spongiosa region of each phantom vertebra were measured using DEQCT and dual energy x-ray absorptiometry (DEXA). Lastly, BMC was measured in a patient using DEQCT and DEXA. Measured values of hydroxyapatite fraction and nominal values in the homemade phantom showed a good correlation. The relative error remained below 14.2%. Quantification of BMC (in whole vertebra) and BMD (in spongiosa) in the ESP showed a good agreement between measured values and nominal values. The relative error remained between 0.7% and 7.5% for BMCSPECT/CT, 1.1% and 7.7% for BMCDSCT, 5.4% and 32.0 for BMDSPECT/CT, and 59.4% and 10.0% for BMDDSCT. Quantification of BMC in lumbar vertebrae 1 and 2 of a patient showed relative errors of 7.6% and -8.4% between DEXA and DSCT. Our study shows that DEQCT using a mass fraction method (phantomless) enables quantification of hydroxyapatite in a clinical nuclear medicine setting. An overestimation of the hydroxyapatite volume fraction was observed in all quantified regions, in particular in the spongiosa region of ESP. This result might be related to insufficient information about the x-ray spectra and the detector sensitivity function.


[Cellular injury associated with extracorporeal circulation].
Circulation of blood extracorporeally through plastic tubing causes severe shear stresses to blood cells and activates several regulatory cascades. These various pathways include the cytokine cascades, complement and coagulation. Interleukine-1, -6, -8, tumor necrosis factor-alpha have been implicated. Among various mediators of tissue injury released by activated neutrophils, elastase and metalloproteinases have been considered to be relevant in postoperative organ dysfunction in cardiac operations. Endothelial cells are extremely sensitive to insults that occur during cardiopulmonary bypass (CPB). These insults lead to disruption of barrier function and leukocyte adhesion. Immunoglobulins such as ICAM-1 and VCAM-1 are expressed on endothelium cells and act as ligands for integrins. It is also important to remember that during cardiac operations, the interest on the metabolism of in free radicals has focused on the heart and the lungs because they are exposed to ischemia and subsequent reperfusion. Increased production of free radicals during CPB is associated with myocardial and pulmonary dysfunctions. Now it is well recognized that the whole body inflammatory response induced by CPB is mainly responsible for postoperative organ dysfunctions.


Heterobimetallic metal-complex assemblies constructed from the flexible arm-like ligand 1,1'-bis[(3-pyridylamino)carbonyl]ferrocene: structural versatility in the solid state.
The bidentate ferrocenyl sandwich molecule 1,1'-bis[(3-pyridylamino)carbonyl]ferrocene (3-BPFA) has been employed as an organometallic ligand in reactions with a series of transition metal salts to construct heterobimetallic architectures. X-ray crystallographic characterization reveals that the crystal packing of free ligand 3-BPFA induces spontaneous resolution of helical chains via intermolecular hydrogen bonds. By combining the flexibility from the arm-like molecule (3-BPFA) with the variation of the coordination property from different metal ions and/or the different counteranions, five different types of architectures are prepared: one octahedral coordination cage (copper(II) complex 1); two discrete pseudocapsules for combination of chlorine anions (nickel(II) complex 2 and cobalt(II) complex 3); two dimers with metal-metal interactions (silver(I) complexes 4 and 5); one macrocyclic complex (mercury(II) complex 6); and five two-dimensional mixed-metal-organic frameworks (M'-MOFs) (zinc(II), cadmium(II), and mercury(II) complexes 7-11). The structures of all complexes are characterized in detail by IR, elementary analysis, and single-crystal X-ray diffraction analysis. The factors inducing the structure variation among the complexes are discussed by taking account of the coordination geometry of different metal ions, the span angle between the two "arms", and the coordination mode of the 3-BPFA ligand.


The relationship between aggression in children and locus of control beliefs.
Gender differences are evident in the etiology and maintenance of aggressive behavior (which is on the increase for both male and female youths), but the explanatory models that have been proposed, including social learning theory and information processing models, are more appropriate for boys than for girls. In an attempt to elucidate processes underlying aggression, particularly for girls, the authors explored locus of control as a cognitive variable possibly related to aggressive behavior. The relationships between teacher-reported aggression and 3 types of locus of control (internal, powerful other, and unknown) for success and failure experiences were investigated. For girls, aggressive behavior was positively related to internal and unknown locus of control. In contrast, boys' aggressive behavior was unrelated to internal locus of control beliefs and negatively related to external locus of control beliefs. Possible explanatory mechanisms for the relationship between locus of control beliefs and aggression are discussed. The present study contributes to the understanding of aggression in girls and points to different processes underlying girls' and boys' aggression.


Effects of dimethylsulfoxide on behavior and antioxidant enzymes response of planarian Dugesia japonica.
In this study, the toxicity, behavioral and antioxidant activity effects of dimethylsulfoxide (DMSO) on planarian Dugesia japonica were investigated. The results showed that the mortality was directly proportional to the DMSO concentration, and planarian locomotor velocity decreased as the concentration of DMSO increased. The recovery of the motility for planarians pre-exposed to DMSO was found to be time- and dose-dependent, and only those pre-exposed to 0.1-3% DMSO resulted in full recovery. The antioxidant enzymes of planarians in response to long-term DMSO stress was also altered in a time- and dose-dependent manner. Planarians revealed more tolerance to DMSO toxicity at low DMSO (0.1%) level in short- and long-term DMSO stress, in which an efficient antioxidant system was involved and the motility was not affected.


Functional effects of the purinergic innervation of the rabbit urinary bladder.
Although it is generally agreed that micturition is primarily under the control of the parasympathetic nervous system, there is good evidence that an atropine insensitive, nonadrenergic-noncholinergic neuronal component exists. Recent evidence indicates that the purinergic transmitter ATP (or an other purinergic analog) may be responsible for the atropine-insensitive portion of the contraction. Although isolated muscle strip studies have identified the purinergic response, the functional significance of this response has not been determined. Utilizing an in vitro whole-bladder model, we have investigated the functional ability of the purinergic component of field stimulation to empty the bladder under standard conditions. The results indicate: the response of the bladder to both cholinergic stimulation and field stimulation is characterized by a rapid rise in intravesical pressure followed by a prolonged plateau phase; expulsion of fluid from the bladder occurs primarily during the plateau phase of the contraction; in the presence of atropine, field stimulation produces only a transient rapid rise in tension, similar to the response to exogenous ATP; and this "purinergic" response does not result in significant bladder emptying. These results suggest that the bladder response to this purinergic stimulation may be complimentary to, but functionally different from that which occurs in response to cholinergic transmission alone.


Metabolic changes after a hypocaloric, low-glycemic-index diet in obese children.
A low glycemic index (LGI) diet has been proposed as a treatment for obesity in adults; few studies have evaluated LGI diets in obese children. The purpose of the study was to compare the effects of two diets, with similar energy intakes, but different glycemic indexes in a pediatric outpatient setting. A parallel- group, randomized controlled trial was conducted, and 22 obese outpatient children with a body mass index (BMI) Z-score >2 (11 females and 11 males, BMI 28.9±2.9 kg/m²) were included in the study. Patients were randomly allocated to a hypocaloric LGI (GI:60), or to a hypocaloric high glycemic index (HGI) diet (GI:90). The LGI and HGI diets were almost equivalent for macronutrient composition. Anthropometric and biochemical parameters were measured at baseline and after 6 months. In both groups there were significant decreases in BMI, BMI Z-score, blood pressure, and high-sensitivity C-reactive protein. Only LGI diets produced a significant decrease in waist circumference and homeostasis model assessment. Analysis of variance demonstrated that the BMI Z-score decrease from baseline values was significantly greater after the LGI diet than after the HGI diet [-0.20 (95% confidence interval (CI) -0.29 to -0.10) vs -0.34 (95%CI -0.43 to -0.24)], mean difference between groups -0.14 (95%CI -0.27 to -0.01), p<0.05). Changes in triglyceride concentrations were significantly lower in LGI as compared to HGI diet (p<0.05). This study demonstrates that a hypocaloric LGI diet has beneficial metabolic effects in comparison to a hypocaloric HGI diet in obese children.


[Some key issues about scientific research on traditional Chinese medicine].
Since the Tenth Five-Year Plan in China, the science and technology of traditional Chinese medicine (TCM) has gained unprecedented high attention, and at the same time, the people who have been engaging in the TCM research are bearing more and more missions and responsibilities. In order to get more significant breakthroughs and scientific achievements with great innovation, great value and great influence in the near future, the radical target and strategy for TCM research should be made out as follows: sifting out the lees, laying aside the disputes, tamping the identical opinions, and innovating to apply. In other words, the principle that "to do what can be done, not to do what can not be done; to do what should be done, not to do what should not be done, and to pay more attention to standardization than to innovation" should be recognized unequivocally. The six issues such as the evaluation and improvement of TCM efficacy, the safety evaluation and reasonable usage of TCM, the innovation and development of TCM quality evaluation and control technology, the sustainable utilization and protection of TCM resources, the elucidation and modernization of TCM basic theory, etc. should be considered as the prior and key aspects of TCM research in the following 20 years in China.


Stability of Dilute Colloidal Silica Suspensions in the Vicinity of the Binodal Curve of the System 2-Butoxyethanol/Water
In the temperature-composition diagram of the system 2-butoxyethanol (abbreviated C4E1)/water, SiO2 [mass fraction of SiO2, y(SiO2) approximately 0.01; volume fraction phi(SiO2) approximately 10(-3)] there exists a flocculation temperature-composition curve running below the binodal curve for x > xc (x, mole fraction of C4E1; xc = 0.0598). The concentration of the colloidal particles is low enough to consider them an "impurity." In the region of the phase diagram bound by the binodal and the flocculation curve the suspension of the colloidal SiO2 particles is unstable and the particles flocculate reversibly. The difference between the temperature of phase separation and the flocculation temperature increases with increasing values of x - xc up to a maximum value of x (xmax). For x > xmax the suspensions are unstable at all temperatures studied. For x < xc the suspension of the SiO2 particles is stable up to the temperature of phase separation of the C4E1/water mixture. The flocculation curve is assumed to reflect the influence of local concentration fluctuations with long range correlations on the stability of the SiO2 suspensions. For x > xc these concentration fluctuations are water rich and interact with the hydrophilic surface of the colloidal SiO2 particles by forming an adsorption layer. This layer is assumed to modify the interparticle potential energy-distance curve and to trigger flocculation. For x < xc the concentration fluctuations are C4E1 rich and no adsorption layer is formed at the hydrophilic surface of the colloidal particles. Copyright 1997Academic Press


Short-term changes in sleep duration and risk of type 2 diabetes: Kailuan prospective study.
Evidence suggests short or long sleep duration is associated with a higher risk of diabetes. Using a large longitudinal data set spanning 2 years, we examined whether a change in sleep duration is associated with diabetes.Current analysis included 56,588 participants who were free of diabetes during both 2006-2007 (exam1) and 2008-2009 (exam2). Sleep duration was categorized into 7 groups: ≤5.5 hours, 6.0 to 6.5 hours, 7.0 hours, 7.5 to 8.0 hours, ≥8.5 hours, decrease ≥2 hours, and increase ≥2 hours. Cox proportional hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CI) for diabetes, according to sleep duration.Compared to the reference group of persistent 7-h sleepers, participants who slept 7.5 to 8 hours per night (HR, 1.20; 95% CI, 1.02-1.40), ≥8.5 hours per night (HR, 1.37; 95% CI, 1.03-1.81) and an increase of ≥2 hours sleep per night (HR, 1.24; 95% CI, 1.05-1.48) were all associated with an increased risk of developing diabetes in analyses adjusted for age, sex, education level, income level, smoking status, drinking status, physical activity, BMI, snoring status, hypertension, hyperlipidemia, and family history of diabetes. The abovementioned associations of sleep duration and incident diabetes were only prominent among individuals aged <64 years.This study suggests that individuals whose sleep duration increases ≥2 hours per night are at an increased risk of diabetes.


Core decompression for osteonecrosis of the femoral head.
A retrospective++ review of core decompression of the femoral head for treatment of osteonecrosis was done. Cause of osteonecrosis, radiographic stage and progression, complications, and clinical results were evaluated. The study was based on 54 hips in 45 patients (98.2% followup rate). All patients reported pain preoperatively. Thirty-five hips (30 patients) were considered to have failed. Of these, 26 hips (23 patients) underwent total hip arthroplasty. The remaining 9 hips (7 patients) had little or no relief of pain and no improvement in function, but had not undergone total hip arthroplasty at last followup. The average time to failure was 11.1 months (2-34 months). Nineteen hips (16 patients) were considered successful. Fifteen hips (12 patients) were graded good to excellent and 4 hips (4 patients) were graded fair in terms of clinical results with an average followup of 47.5 months (12.4-95.7 months). The mean preoperative Hospital for Special Surgery hip score improved from 24.6 points (range, 18-38 points) to 34.2 points (range, 20-40 points). There were 2 intertrochanteric femur fractures in this group (5 and 6 weeks postoperatively). The overall success rate of core decompression in this series was 35.2% (19 of 54 hips, 45 patients). The results of core decompression in this study were poor in general and had an unpredictable effect on disease progression.


A new species of Apostolepis (Serpentes, Dipsadidae, Elapomorphini) from the Cerrado of Central Brazil.
We describe a new species of the genus Apostolepis found near São Salvador Hydroelectric Power Plant, municipality of São Salvador do Tocantins, in the central Cerrado ecoregion. The new species is distinguished from its congeners by the following combination of characters: presence of eleven dorsolateral stripes, five infralabial scales and the lack of preoculars scales. The new species shares some external characteristics mainly with A. arenaria, A. gaboi and A. nelsonjorgei, with which it is compared.


The impact of donor and recipient hepatitis B surface antigen status on liver disease and survival in renal transplant recipients.
Ninety-eight renal transplant recipients who had been followed for 1-6.5 years (median 3.2 years) were reviewed to determine the effect of donor and recipient hepatitis B surface antigen status on the incidence of hepatitis and on patient survival. The cumulative risk of developing hepatitis posttransplant was significantly higher in hepatitis B surface antigen-positive versus hepatitis B surface antigen-negative patients (P = 0.001). Nine (60%) of 15 patients who were hepatitis B surface antigen-positive prior to transplantation, 3 (75%) of 4 patients who became hepatitis B surface antigen-positive after transplantation, and 17 (22%) of 79 patients who were persistently hepatitis B surface antigen-negative developed hepatitis posttransplant. Five hepatitis B surface antigen-negative patients received allografts from hepatitis B surface antigen-positive donors. None of the five, including one who was initially seronegative, became hepatitis B surface antigen-positive posttransplant. Of the four patients who became HBsAg-positive posttransplant, three received kidneys from donors of unknown HBsAg status in China, while one was transplanted with a kidney from a HBsAg-negative donor. In summary, we found that the risk of developing hepatitis after renal transplantation was significantly higher in hepatitis B surface antigen-positive patients. However, both patient and graft survival were similar in hepatitis B surface antigen-positive and hepatitis B surface antigen-negative patients. The transplantation of kidneys from HBsAg-positive donors to HBsAg-negative patients did not result in clinically significant hepatitis or chronic HBsAg carriage. De novo hepatitis B infection may arise from sources other than the kidney itself.


Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model.
Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS) in diabetic nephropathy (DN) patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model. A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1) in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules. The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated. The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.


Role of steroid hormones and growth factors in breast cancer.
Breast cancer is the most common cancer in women worldwide and its incidence is increasing. Oestrogens and mitogenic growth factors may play an important role in the development of breast cancer, whereas inhibitory growth factors may prevent the development of breast cancer. Only about 5 to 10% of cases of breast cancer are due to inheritance of mutations in the BRCA1 or BRCA2 tumour suppressor genes. Mutations in the p53 tumour suppressor gene are commonly found in sporadic breast cancers. Retinoic acid and carotenoids may play a protective role in breast cancer since they inhibit the growth of the oestrogen receptor-positive MCF-7 breast cancer cell line. The presence of oestrogen and progesterone receptors predicts the likelihood of benefit from hormonal therapy. Amplification of the c-erbB2 oncogene in breast cancers is associated with a poor prognosis. It is now apparent that there is a complex, productive cross-talk between oestrogen-directed and growth factor-directed pathways which are believed to markedly reinforce their individual cellular effects on growth and gene responses.


Rapid ultraperformance liquid chromatography-tandem mass spectrometry method for quantification of oxcarbazepine and its metabolite in human plasma.
A rapid and sensitive ultraperformance liquid chromatography tandem mass spectrometry assay was developed for the simultaneous analysis of oxcarbazepine and its main metabolite in human plasma. The assay involves a simple solid-phase extraction procedure of 0.3 mL of human plasma and analysis was performed on a triple-quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionization. Separation was achieved on an Acquity UPLC™ BEH C₁₈ column (50 × 2.1 mm, i.d., 1.7 µm) with isocratic elution at a flow-rate of 0.25 mL/min and imipramine was used as the internal standard. The standard calibration curve was linear over the range 9.580-5070.205 ng/mL for oxcarbazepine (OXC) and 19.444-10290.800 ng/mL for 10,11-dihydro-10-hydroxycarbamazepine (MHD), expressed by the linear correlation coefficient r², which was better than 0.995 for OXC and MHD. The intra- and inter-day precision and accuracy of the quality control samples were within 10.0%. The recoveries were 81.0, 89.6 and 66.6% for OXC, MHD and imipramine, respectively. The total run time was 1.5 min only for each sample, which makes it possible to analyze more than 350 samples per day.


Comparison of neuropsychological functioning in Alzheimer's disease and frontotemporal dementia.
Neuropsychological changes distinguishing mild Alzheimer's disease (AD) from frontotemporal dementia (FTD) have been described, but empirical verification of differential cognitive characteristics is lacking. Archival neuropsychological data on 15 FTD patients, 16 AD patients, and 16 controls were compared. Controls outperformed both patient groups on measures of verbal and nonverbal memory, executive ability, and constructional skill, with AD patients showing more widespread memory decline. No differences were found between the 3 groups in confrontation naming, recognition memory, or basic attention. Patient groups differed only in nonverbal memory, with FTD patients performing significantly better than AD patients. However, patient groups also differed in pattern of performance across executive and memory domains. Specifically, AD patients exhibited significantly greater impairment on memory than executive tasks, whereas the opposite pattern characterized the FTD group. These findings suggest that examination of relative rankings of scores across cognitive domains, in addition to interpretation of individual neuropsychological scores, may be useful in differential diagnosis of FTD versus AD.


Transcranial flavoprotein fluorescence imaging of mouse cortical activity and plasticity.
Endogenous fluorescence signals derived from mitochondria reflect activity-dependent changes in brain metabolism and may be exploited in functional brain imaging. Endogenous flavoprotein fluorescence imaging in mice is especially important because many genetically manipulated strains of mice are available and the transparent skull of mice allows transcranial fluorescence imaging of cortical activities. In the primary sensory areas of mice, cortical activities and experience-dependent plasticity have been investigated using transcranial fluorescence imaging. Furthermore, differential imaging, based on stimulus specificity of cortical areas, distinguished activities in higher visual areas around the primary visual cortex from those in primary visual cortex. The combination of transcranial fluorescence imaging with the suppression of cortical activities using photobleaching of flavoproteins is expected to aid in elucidating the roles of sensory cortices including higher areas in mice.


[A case of total hip arthroplasty for femoral head necrosis while using satralizumab for neuromyelitis optica spectrum disorders].
A 47-year-old woman developed right femoral head necrosis during long-term steroid use for neuromyelitis optica spectrum disorder. She underwent a total hip arthroplasty because her right hip pain persisted after satralizumab treatment. There were no postoperative infections. Under oral administration of tacrolimus 3 mg, prednisolone 11 mg, and acetaminophen 2,275 mg, her postoperative body temperature was less than 38°C and normalized in about 2 days after the operation. No parameters indicating worsening of inflammation were observed in the blood test. In satralizumab-treated patients, infection cannot be ruled out even without inflammatory findings. In particular, if a slight fever of the 37°C-range or a mildly high white blood cell count persists, paying attention to signs of infection and actively investigating the presence or absence of infection using medical image diagnostic devices are necessary.


Free-space photonic switching architectures based on extended generalized shuffle networks.
A new class of networks that is well suited for free-space photonic switching applications is described. These networks are known as extended generalized shuffle networks. It is shown that these networks can provide low blocking probabilities while requiring low hardware costs. In fact, if sufficient hardware is added to these networks, they become strictly nonblocking networks (with blocking probabilities equal to zero). The hardware cost of an extended generalized shuffle network can be modified to yield any desired blocking probability, so cost-effective designs are possible. In addition, it is shown that these networks are extremely fault tolerant, and they can also be designed to have high system availabilities. Because the networks can use various types of interconnections to connect the nodes and because the nodes can have various types of functionality, these networks also provide high degrees of flexibility that can be used to optimize a free-space photonic design. The design of extended generalized shuffle networks based on a particular node type that is easy to implement with symmetric self-electro-opticeffect devices is studied.


Mapping the maintenance stage of recovery: a qualitative study among treated and non-treated former alcohol dependents in Poland.
The study provides an in-depth qualitative understanding of the maintenance stage when recovering from alcohol dependence with a focus on the broader social context of change of addictive behaviour. It explores the recovery as a subjective process within the abstinence-oriented Polish treatment system organized on the basis of the Minnesota model and is probes for group differences between treated and non-treated populations. The study is based on qualitative data from a media-recruited sample of 29 treated and non-treated former alcohol dependents (ICD-10) in Warsaw/Poland 2006/2007. They reported a recovery time of at least 2 years (M(recovery) = 11, SD = 9). In-depth, semi-structured interviews were analysed according to the problem-centred interview method using ATLAS.ti software. A wide range of maintenance strategies potentially contributing to the stabilization of recovery from alcohol dependence was identified. However, from the respondents' point of view, the change process is contingent upon the subjective weighing of specific maintenance factors and the importance attributed to their interplay. This includes time management as well as one's ability to invest available resources and strengths in shaping and pursuing personal goals. More commonalities than differences can be observed between groups during the maintenance stage, regardless of respondents' type of the pathway out of addiction. However, when confronting professional concepts of recovery with subjective accounts, only a subgroup conforms to the invasive, potentially normative definitions of recovery, while others do not link their recovery with identity transformation.


Root Respiration and Growth in Plantago major as Affected by Vesicular-Arbuscular Mycorrhizal Infection.
Effects of vesicular-arbuscular mycorrhizal (VAM) infection and P on root respiration and dry matter allocation were studied in Plantago major L. ssp. pleiosperma (Pilger). By applying P, the relative growth rate of non-VAM controls and plants colonized by Glomus fasciculatum (Thaxt. sensu Gerdemann) Gerdemann and Trappe was increased to a similar extent (55-67%). However, leaf area ratio was increased more and net assimilation rate per unit leaf area was increased less by VAM infection than by P addition. The lower net assimilation rate could be related to a 20 to 30% higher root respiration rate per unit leaf area of VAM plants. Root respiration per unit dry matter and specific net uptake rates of N and P were increased more by VAM infection than by P addition. Neither the contribution of the alternative respiratory path nor the relative growth rate could account for the differences in root respiration rate between VAM and non-VAM plants. It was estimated that increased fungal respiration (87%) and ion uptake rate (13%) contributed to the higher respiratory activity of VAM roots of P. major.


Immunohistochemical study of sensory nerve formations in human glabrous skin.
The sensory nerve formations (or corpuscles) of normal human glabrous skin from hand and fingers, obtained by punch biopsies, were studied by the streptavidin-biotin method using monoclonal antibodies directed against neurofilament protein (NFP), S-100 protein, glial fibrillary acidic protein (GFAP), cytokeratins, and vimentin. NFP immunoreactivity (IR) was observed in the central axons of most sensory formations, while S-100 protein IR was restricted to non-neuronal cells forming the so-called inner cells core or lamellar cells. Furthermore, vimentin IR was found in the same cells of Meissner's and glomerular corpuscles. None of the sensory nerve formations were stained for GFAP or keratin. The present results suggest that the main nature of the intermediate filaments of the non-neuronal cells of sensory nerve formations from human glabrous skin is represented by vimentin and not by GFAP. Thus, our findings suggest that lamellar and inner core cells of SNF are modified and specialized Schwann cells and not epithelial or perineurial derived cells.


Novel Immunity Proteins Associated with Colicin M-like Bacteriocins Exhibit Promiscuous Protection in Pseudomonas.
Bacteriocins related to colicin M, acting via cleavage of the cell wall precursor lipid II, have been characterized in γ- and β-proteobacteria. Depending on the species, immunity is provided by either an inner membrane-anchored periplasmic protein or by an integral membrane protein. In Pseudomonas however, the immunity partner of colicin M-like bacteriocins remains unknown. Based on an in silico analysis in pseudomonad genomes, we here identify a gene encoding a putative immunity partner that represents a novel type of integral membrane protein (PmiA, Pseudomonas colicin M-like immunity type A). By heterologous expression of pmiA genes in susceptible strains, we show that immunity to colicin M-like bacteriocins is indeed provided by the cognate PmiA. Sequence homology among PmiA proteins is essentially absent, except for a short motif with a conserved periplasm-exposed aspartate residue. However, PmiA's protective function is not abolished by changing this acidic residue to the uncharged alanine. Immunity by PmiAs appears promiscuous to the extent that PmiA homologs from a clade sharing <40% pairwise amino acid identity, equally provide protection against the bacteriocin linked to the original PmiA. This study shows that multiple immunity factors have evolved independently to silence lipid II-targeting enzymatic bacteriocins. Their relaxed bacteriocin immunization capacity contrasts to the strict specificity of immunity proteins shielding the enzymatic domain of nuclease bacteriocins. The nature of associated immune functions needs consideration when using such natural protein antibiotics or designing novel variants.


Sequestration of tau by granulovacuolar degeneration in Alzheimer's disease.
Antibodies directed against three regions of tau have been used in a histologic study of granulovacuolar degeneration (GVD) in Alzheimer's disease (AD). Granulovascular degeneration complexes, consisting of a dense granule in a less-dense vacuole, were found in hippocampal pyramidal neurons in all patients studied. Anti-tau antibodies directed against the N-and C-termini, and the repeat region of tau, were found to immunolabel the granule of the GVD complex. Intracellular neurofibrillary tangles also were labeled by these antibodies. In particular, MAb6.423, which recognizes tau protein sequestered in paired helical filaments (PHF) in AD, but not the normal tau proteins so far described in human brain, labeled GVD granules. Contrarily, a generic tau marker (MAb7.51), which immunolabels all known isoforms of isolated and expressed tau protein, including PHF-tau, did not label the GVD granule. These findings demonstrate that the entire tau molecule is sequestered within the GVD granule, and that the tau protein found in GVD complexes is antigenically related to that found in PHFs. There is, however, a difference in the way in which the repeat region of tau is incorporated into the two structures, making the MAb7.51 epitope unavailable in the GVD complex. These findings suggest that the formation of GVD complexes in hippocampal pyramidal neurons vulnerable to neurofibrillary degeneration may represent an alternative pathway for dealing with an aberrant molecular complex, which contributes to the formation of GVD granules and neurofibrillary tangles in AD.


Lumbar Facet Joint Cyst Treated With Decompression and Interlaminar Stabilization.
Spinal facet joint cysts (FJCs) are an increasingly reported cause of lower back pain, radiculopathy, and neurological deficits owing to their proximity to adjacent nerve roots. The etiology of these cysts has not yet been fully elucidated, although they appear to be related to degenerative changes in the facet joints themselves. Conservative management strategies including physical therapy and oral analgesics rarely result in spontaneous regression of an FJC, often providing only short-term relief. The current treatment modalities reported for FJCs generally range from percutaneous cyst aspiration to decompression surgery with or without instrumented spinal fusion. However, instrumented fusion often results in a higher rate of complications such as pseudoarthrosis and adjacent segment disease. The Coflex® (Paradigm Spine, LLC, New York, NY) interlaminar stabilization (ILS) implant is a novel titanium, U-shaped device which acts as a motion-preserving stabilizer and has proven to be a viable alternative to instrumental fusion. Here, we discuss a case of an FJC treated with both decompression and placement of a Coflex ILS device.


Multicenter prospective observational study of the comparative efficacy and safety of vancomycin versus teicoplanin in patients with health care-associated methicillin-resistant Staphylococcus aureus bacteremia.
The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 μg/ml (MIC50 and MIC90, 1.5 μg/ml), and the TEC MIC ranged from 0.5 to 8 μg/ml (MIC50, 3 μg/ml; MIC90, 6 μg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.


Calcineurin is expressed and plays a critical role in inflammatory arthritis.
Calcineurin is a calcium-activated phosphatase to mediate lymphocyte activation and neuron signaling, but its role in inflammatory arthritis remains largely unknown. In this study, we demonstrate that calcineurin was highly expressed in the lining layer, infiltrating leukocytes, and endothelial cells of rheumatoid synovium. The basal expression levels of calcineurin were higher in the cultured synoviocytes of rheumatoid arthritis patients than those of osteoarthritis patients. The calcineurin activity in the synoviocytes was increased by the stimulation with proinflammatory cytokines such as IL-1beta and TNF-alpha. Moreover, rheumatoid arthritis synoviocytes had an enlarged intracellular Ca(2+) store and showed a higher degree of [Ca(2+)](i) release for calcineurin activity than osteoarthritis synoviocytes when stimulated with either TNF-alpha or phorbol myristate acetate. IL-10, an anti-inflammatory cytokine, failed to increase the Ca(2+) and calcineurin activity. The targeted inhibition of calcineurin by the overexpression of calcineurin-binding protein 1, a natural calcineurin antagonist, inhibited the production of IL-6 and matrix metalloproteinase-2 by rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor, cyclosporin A. Moreover, the abundant calcineurin expression was found in the invading pannus in the joints of mice with collagen-induced arthritis. In these mice, calcineurin activity in the cultured synovial and lymph node cells correlated well with the severity of arthritis, but which was suppressed by cyclosporin A treatment. Taken together, our data suggest that the abnormal activation of Ca(2+) and calcineurin in the synoviocytes may contribute to the pathogenesis of chronic arthritis and thus provide a potential target for controlling inflammatory arthritis.


Correlation of estradiol in pregnancy and anterior cruciate ligament laxity.
The purpose of this study was to determine whether a correlation existed between estradiol in pregnancy and laxity of the anterior cruciate ligament by measuring anterior tibial translation. All patients underwent measurement of anterior tibial translation using KT-1000 knee arthrometer testing and serum estradiol determination during the third trimester of pregnancy and postpartum. Forty knees were studied. The average serum estradiol levels decreased from 10,755.0 ng/L to 50.3 ng/L. There was an average decrease anterior tibial translation with a manual maximum displacement of 3.0 mm (range, 1 mm-5 mm) from the first to second examinations. Average measurement of anterior tibial translation in pregnant women showed a statistically significant increase in laxity in the third trimester of pregnancy compared with the postpartum laxity. The results of this study show that high serum estradiol levels during the third trimester of pregnancy correlate with increased anterior tibial translation and that this anterior tibial translation decreases with the return of serum estradiol to nonpregnant levels.


Improved Flame-Retardant and Ceramifiable Properties of EVA Composites by Combination of Ammonium Polyphosphate and Aluminum Hydroxide.
Ceramifiable flame-retardant ethylene-vinyl acetate (EVA) copolymer composites for wire and cable sheathing materials were prepared through melt compounding with ammonium polyphosphate (APP), aluminum hydroxide (ATH) and fluorophlogopite mica as the addition agents. The effects of ammonium polyphosphate, alumina trihydrate, and APP/ATH hybrid on the flame retardant, as well as on the thermal and ceramifiable properties of EVA composites, were investigated. The results demonstrated that the composites with the ratio of APP:ATH = 1:1 displayed the best flame retardancy and the greatest char residues among the various EVA composites. The tensile strength of the composites was 6.8 MPa, and the residue strength sintered at 1000 °C reached 5.2 MPa. The effect of sintering temperature on the ceramifiable properties, microstructures, and crystalline phases of the sintered specimen was subsequently investigated through X-ray diffraction, Fourier transform infrared, and scanning electron microscopy. The XRD and FTIR results demonstrated that the crystal structure of mica was disintegrated, while magnesium orthophosphate (Mg₃(PO₄)₂) was simultaneously produced at an elevated temperature, indicating that the ceramization of EVA composites had occurred. The SEM results demonstrated that a more continuous and compact microstructure was produced with the rise in the sintering temperature. This contributed to the flexural strength improvement of the ceramics.


Cardiopulmonary exercise testing in neuromuscular disease: a systematic review.
Cardiopulmonary exercise testing (CPET) is increasingly used to determine aerobic fitness in health and disability conditions. Patients with neuromuscular diseases (NMDs) often present with symptoms of cardiac and/or skeletal muscle dysfunction and fatigue that might impede the ability to deliver maximal cardiopulmonary effort. Although an increasing number of studies report on NMDs' physical fitness, the applicability of CPET remains largely unknown. This systematic review synthesized evidence about the quality and feasibility of CPET in NMDs and patient's aerobic fitness. The review followed the PRISMA guidelines (PROSPERO number CRD42020211068). Between September and October 2020 one independent reviewer searched the PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science databases. Excluding reviews and protocol description articles without baseline data, all study designs using CPET to assess adult or pediatric patients with NMDs were included. The methodological quality was assessed according to the American Thoracic Society/American College of Chest Physicians (ATS/ACCP) recommendations. CPET is feasible for ambulatory patients with NMDs when their functional level and the exercise modality are taken into account. However, there is still a vast potential for standardizing and designing disease-specific CPET protocols for patients with NMDs. Moreover, future studies are urged to follow the ATS/ACCP recommendations.


Thymolipoma. A report of nine cases, with emphasis on its association with myasthenia gravis.
Thymolipomas are rare tumors of the anterior mediastinum accounting for up to 9% of all thymic tumors. These tumors are associated with autoimmune diseases in up to 50% of the patients, including myasthenia gravis, aplastic anemia, hypogammaglobulinemia, lichen planus, and Graves' disease. These tumors with a fatty appearance also can arise in older patients with autoimmune disease. This retrospective study evaluated the thymolipomas from nine patients at a single institution, which were resected between 2002 and 2007. The clinical data as well as radiologic findings were evaluated, together with the follow-up. Seven patients initially presented with myasthenia gravis, and therefore they underwent a resection of the thymus, even though imaging techniques did not reveal a tumor in any of the cases. Another patient showed no symptoms of autoimmune disease for 20 years, and though cardiomegaly was suspected, further investigation revealed a thymolipoma. The symptoms of myasthenia gravis improved following the surgery in one patient. During follow-up, one patient died due to esophageal cancer, and the remaining patients are alive without recurrence. Thymolipomas are benign tumors that show an excellent outcome. Patients with autoimmune disease symptoms occasionally show an improvement of the symptoms after a resection of the tumors.


Hyperalimentation order calculations using a computer.
Dispensing hyperalimentation orders in a timely and correct manner can be demanding for staff pharmacists. Using a computer to calculate the amounts of amino acid, dextrose, and electrolyte solutions can greatly reduce pharmacy response time and insure accuracy in filling the physician's order. This report lists a computer program that will do these calculations and also gives consideration to the technical aspects of using the program.


Meningiomas and neurofibromatosis.
Neurofibromatosis type 2 (NF2) is a rare genetic disorder predisposing to multiple benign tumors of the nervous system. Meningiomas occur in about half of NF2 patients, and are often multiple. Patients harboring seemingly isolated multiple meningiomas should be investigated to diagnose NF2 by careful familial history collection, detailed clinical examination (skin lesions and slit lamp examination of the lens), audiovestibular testing, and fine cranio-spinal Magnetic Resonance Imaging. Somatic mosaicism is frequent in NF2 and may explain a mild phenotype as, e.g. isolated multiple meningiomas. Neurofibromatosis type 1 is not associated with an increased risk of meningioma. Whether meningiomas are part of the schwannomatosis tumor phenotype or not remains debated. Meningiomas in NF2 patients are associated with a higher risk of mortality, and their treatment is challenging, but data about natural history of meningiomas in NF2 patients in the literature are sparse. Thus, knowledge of tumor behavior is essential in slow growing tumors like meningiomas, to balance the risk of treatment against the natural history of the disease, and to evaluate the efficiency of alternative therapeutics (radiation therapy or new drugs).


Enhanced photoluminescence of boron nitride quantum dots by encapsulation within polymeric nanoparticles.
Boron nitride quantum dots (BNQDs) have been proposed as probes for bioimaging owing their to outstanding photoluminescent properties, although their hydrophobic nature and strong aggregation tendency in aqueous media limit their application in the biomedical field. In this work, we synthesize BNQDs by a liquid exfoliation-solvothermal process under pressure from boron nitride nanoparticles in N,N-dimethylformamide. The BNQDs display an average size of 3.3 ± 0.6 nm, as measured by transmission electron microscopy, and a (100) crystalline structure. In addition, a quantum yield of 21.75 ± 0.20% was achieved. To ensure complete dispersibility in water and prevent possible elimination by renal filtration upon injection, the BNQDs (20% w/w) are encapsulated within poly(ethylene glycol)-b-poly(epsilon-caprolactone) nanoparticles by a simple and scalable nanoprecipitation method, and hybrid nanocomposite particles with significantly stronger photoluminescence than their free counterparts are produced. Finally, their optimal cell compatibility and bioimaging features are demonstrated in vitro in murine macrophage and human rhabdomyosarcoma cell lines.


Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload.
Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial hypertrophy and heart failure. The aim of this study was to investigate the role of cardiac Fstl1 in the remodeling response to pressure overload. Cardiac myocyte-specific Fstl1-KO mice were constructed and subjected to pressure overload induced by transverse aortic constriction (TAC). Although Fstl1-KO mice displayed no detectable baseline phenotype, TAC led to enhanced cardiac hypertrophic growth and a pronounced loss in ventricular performance by 4 wk compared with control mice. Conversely, mice that acutely or chronically overexpressed Fstl1 were resistant to pressure overload-induced hypertrophy and cardiac failure. Fstl1-deficient mice displayed a reduction in TAC-induced AMP-activated protein kinase (AMPK) activation in heart, whereas Fstl1 overexpression led to increased myocardial AMPK activation under these conditions. In cultured neonatal cardiomyocytes, administration of Fstl1 promoted AMPK activation and antagonized phenylephrine-induced hypertrophy. Inhibition of AMPK attenuated the antihypertrophic effect of Fstl1 treatment. These results document that cardiac Fstl1 functions as an autocrine/paracrine regulatory factor that antagonizes myocyte hypertrophic growth and the loss of ventricular performance in response to pressure overload, possibly through a mechanism involving the activation of the AMPK signaling axis.


Persistence of tri-trophic interactions in seasonal environments.
The interplay between species interactions and environmental variation is well-understood for pairwise interactions but not for multi-trophic interactions. Understanding how such interactions persist in a thermally variable environment is particularly important given that most biodiversity on the planet consists of ectotherms whose body temperature depends on the environmental temperature. Here we present a trait-based mathematical framework for investigating how tri-trophic food chains persist in seasonal environments. We report two key findings. First, the persistence of the tri-trophic interaction is enhanced if species at upper trophic levels (e.g. top predators) are more cold-adapted than those at lower levels (e.g. basal resources) by virtue of lower thermal optima, wider response breadths and lower mortality within the favourable temperature range. The important implication is that the assembly and persistence of multi-trophic interactions requires that species at lower trophic levels be somewhat maladapted to their ambient thermal environment, as in the case of recent invasions. Second, differential sensitivity to thermally varying environments provides a mechanistic explanation for the conflict of interest between the intermediate consumer and top predator. The same cold-adaptations that increase the consumer's ability to increase when rare deter the predator's ability to do so. Thus, being well-adapted to its thermal environment makes the intermediate consumer better able to acquire resources and avoid predators. We predict that the hierarchy in cold-adaptation should constrain the number of trophic levels that can be supported in a given thermal environment, and that ectotherm food chain lengths should increase with increasing latitude because larger-amplitude seasonal fluctuations generate more opportunities for species to diverge in their thermal optima.


A frameshift mutation in MC1R and a high frequency of somatic reversions cause black spotting in pigs.
Black spotting on a red or white background in pigs is determined by the E(P) allele at the MC1R/Extension locus. A previous comparison of partial MC1R sequences revealed that E(P) shares a missense mutation (D121N) with the E(D2) allele for dominant black color. Sequence analysis of the entire coding region now reveals a second mutation in the form of a 2-bp insertion at codon 23 (nt67insCC). This mutation expands a tract of six C nucleotides to eight and introduces a premature stop codon at position 56. This frameshift mutation is expected to cause a recessive red color, which was in fact observed in some breeds with the E(P) allele present (Tamworth and Hereford). RT-PCR analyses were conducted using skin samples taken from both spotted and background areas of spotted pigs. The background red area had transcript only from the mutant nt67insCC MC1R allele, whereas the black spot also contained a transcript without the 2-bp insertion. This indicates that black spots are due to somatic reversion events that restore the frame and MC1R function. The phenotypic expression of the E(P) allele is highly variable and the associated coat color ranges from red, red with black spots, white with black spots, to almost completely solid black. In several breeds of pigs the phenotypic manifestation of this allele has been modified by selection for or against black spots.


Proportion of gynecologic cancer patients using complementary and alternative medicine.
Complementary and alternative medicine (CAM) for treatment of cancer and for supportive care of cancer patients must be clearly separated. There is encouraging evidence for CAM in the latter area, such as acupuncture and progressive muscle relaxation for chemotherapy-related nausea and vomiting, and aromatherapy for decreasing anxiety and increasing quality of life. However, there are limited data about CAM used by gynecologic cancer patients, especially in Thai women. Therefore, the authors aimed to investigate the proportion and types of CAM using in our gynecologic cancer patients. This cross-sectional survey was conducted between October to December, 2008. Totals of 50 admitted and 50 walk-in gynecologic cancer patients 1 month after diagnosis, aged more than 20 years and able to give informed consent, were selected for one-by-one interview by random walking survey. Among the 100 interviewed patients, aged 21-69 (mean=50.12), there were 46 cases of cervical cancers, 35 of ovarian cancers, 18 of endometrial cancers (two of these also had ovarian cancers), 2 of malignant gestational trophoblastic diseases, 1 of vulvar cancer, and 1 liver cancer (in a patient with ovarian cancer). Some 67% (95% CI, 57.8-76.2%) of them used CAM. As diet modifications, 11 used Chinese vegetarian, 8 common vegetarian, 5 Cheewajit, and 1 macrobiotics. Five of them used dietary supplements while colonic detoxification was emplyed in three. As herbal medicines, 27 used Thai herbs, 4 Chinese herbs, and 1 a herbal sauna. Twelve were receiving Thai massage. As exercises, 23 used aerobics and 5 stretching. Interestingly, 62 of them used Buddhist praying while only 3 employed native magic. The three most common forms of CAM used by our gynecologic cancer patients were Buddhist praying (62/67, 92.5%), followed by herbal medicines (27/67, 40.3%) and exercises (25/67, 37.3%).


Premalignant lesions in gastric cancer.
Despite a plateau in incidence, gastric cancer is one of the most common cancers worldwide and causes considerable morbidity and mortality. Premalignant gastric lesions are well known risk factors for the development of intestinal-type gastric adenocarcinomas. In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia, and adenoma/dysplasia to gastric carcinoma. This progression is paralleled by a stepwise accumulation of multiple genetic and epigenetic abnormalities. Detection, treatment, and molecular analyses of premalignant lesions may thus provide a basis for gastric cancer prevention. This review describes an overview of current knowledge on premalignant gastric lesions. It also reviews the issue of surveillance of patients with premalignant lesions in order to improve the survival of patients with gastric cancer.


SufE D74R Substitution Alters Active Site Loop Dynamics To Further Enhance SufE Interaction with the SufS Cysteine Desulfurase.
Many essential metalloproteins require iron-sulfur (Fe-S) cluster cofactors for their function. In vivo persulfide formation from l-cysteine is a key step in the biogenesis of Fe-S clusters in most organisms. In Escherichia coli, the SufS cysteine desulfurase mobilizes persulfide from l-cysteine via a PLP-dependent ping-pong reaction. SufS requires the SufE partner protein to transfer the persulfide to the SufB Fe-S cluster scaffold. Without SufE, the SufS enzyme fails to efficiently turn over and remains locked in the persulfide-bound state. Coordinated protein-protein interactions mediate sulfur transfer from SufS to SufE. Multiple studies have suggested that SufE must undergo a conformational change to extend its active site Cys loop during sulfur transfer from SufS. To test this putative model, we mutated SufE Asp74 to Arg (D74R) to increase the dynamics of the SufE Cys51 loop. Amide hydrogen/deuterium exchange mass spectrometry (HDX-MS) analysis of SufE D74R revealed an increase in solvent accessibility and dynamics in the loop containing the active site Cys51 used to accept persulfide from SufS. Our results indicate that the mutant protein has a stronger binding affinity for SufS than that of wild-type SufE. In addition, SufE D74R can still enhance SufS desulfurase activity and did not show saturation at higher SufE D74R concentrations, unlike wild-type SufE. These results show that dynamic changes may shift SufE to a sulfur-acceptor state that interacts more strongly with SufS.


Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future.
Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.


[Risk Management and analysis of an adverse event: accidental patients falls].
The matter of safety of operators and users within health care is becoming more and more topical. The relationship between users and operators with the health structures is a very relevant and expensive circumstance. For this reason some years ago a new culture for clinic risk was born, called risk management (RM), its goal is to create prevention, which focuses on patients and on the risks they take at the moment in which they keep in contact with health structures. We have take into consideration the matter of accidental falls of hospitalized patients occurred in year 2003 at the Hospital of S. Croce of Fano (PU) and made a careful check of the report file prepared by the Health Management of the body mentioned. The unfavorable event we considered is resulted to be of modest entity (0,56% of falls on the total amount of patients hospitalized) uniformly distributed all year long. The most involved patients were male, almost all hospitalized in General Medicine and Geriatrics ward. Most of all individuals fallen down did not produce particular effects. The falls happened commonly during night. Patients who fell down are completely or partially self-supporting. Through a study of all data we collected we defined two variants which interact: on one side the quality of medical assistance, the nurse assistance in particular, and the characteristics of patients fallen down on the other side. Literature too confirm our statements and underline the need to identify the danger points to define the subjects in risk of fall. We found relevant under the present health background to focus our attention on health risks, in particular the accidental fall in hospitals, which has to be considered an important event carry out the monitoring the quality of health assistance.


Role of Endoscopic Ultrasound in Liver Disease: Where Do We Stand?
As the burden of liver disease in the general populace steadily increases, so does the need for both advanced diagnostic and treatment options. Endoscopic ultrasound is a reliable diagnostic and therapeutic method that has an established role, foremost in pancreatobiliary pathology. This paper aims to summarize the growing role of endoscopic ultrasound in hepatology based on the search of the current literature. A number of applications of endoscopic ultrasound are reviewed, including both noninvasive methods and tissue acquisition in focal and diffuse liver disease, portal hypertension measurement, detection and management of gastric and esophageal varices, treatment of focal liver lesions and staging of pancreatobiliary malignancies, treatment of cystic and solid liver lesions, as well as liver abscess drainage. Both hepatologists and endoscopists should be aware of the evolving role of endoscopic ultrasound in liver disease. The inherent invasive nature of endoscopic examination limits its use to a targeted population identified using noninvasive methods. Endoscopic ultrasound is one the most versatile methods in gastroenterology, allowing immediate access with detection, sampling, and treatment of digestive tract pathology. Further expansion of its use in hepatology is immanent.


3D collagen type I matrix inhibits the antimigratory effect of doxorubicin.
The cell microenvironment, especially extracellular matrix proteins, plays an important role in tumor cell response to chemotherapeutic drugs. The present study was designed to investigate whether this microenvironment can influence the antimigratory effect of an anthracycline drug, doxorubicin, when tumor cells are grown in a matrix of type I collagen, a three-dimensional (3D) context which simulates a natural microenvironment. To this purpose, we studied the migratory parameters, the integrin expression, and the activation state of focal adhesion kinase (FAK) and GTPase RhoA involved in the formation of focal adhesions and cell movement. These parameters were evaluated at non toxic concentrations which did not affect HT1080 cell proliferation. We show that while doxorubicin decreased cell migration properties by 70% in conventional two-dimensional (2D) culture, this effect was completely abolished in a 3D one. Regarding the impact of doxorubicin on the focal adhesion complexes, unlike in 2D systems, the data indicated that the drug neither affected beta1 integrin expression nor the state of phosphorylation of FAK and RhoA. This study suggests the lack of antiinvasive effect of doxorubicin in a 3D environment which is generally considered to better mimic the phenotypic behaviour of cells in vivo. Consistent with the previously shown resistance to the cytotoxic effect in a 3D context, our results highlight the importance of the matrix configuration on the tumor cell response to antiinvasive drugs.


A non-death role of the yeast metacaspase: Yca1p alters cell cycle dynamics.
Caspase proteases are a conserved protein family predominantly known for engaging and executing apoptotic cell death. Nevertheless, in higher eukaryotes, caspases also influence a variety of cell behaviors including differentiation, proliferation and growth control. S. cerevisiae expresses a primordial caspase, yca1, and exhibits apoptosis-like death under certain stresses; however, the benefit of a dedicated death program to single cell organisms is controversial. In the absence of a clear rationale to justify the evolutionary retention of a death only pathway, we hypothesize that yca1 also influences non-apoptotic events. We report that genetic ablation and/or catalytic inactivation of Yca1p leads to a longer G1/S transition accompanied by slower growth in fermentation conditions. Downregulation of Yca1p proteolytic activity also results in failure to arrest during nocodazole treatment, indicating that Yca1p participates in the G2/M mitotic checkpoint. 20s proteasome activity and ROS staining of the Delta yca1 strain is indistinguishable from its isogenic control suggesting that putative regulation of the oxidative stress response by Yca1p does not instigate the cell cycle phenotype. Our results demonstrate multiple non-death roles for yca1 in the cell cycle.


Digitized Prenatal Newsletter: Impact on Obstetric Patient Satisfaction and Loyalty.
The high demand for health information from pregnant women has encouraged the creation of an informative program through a weekly digital newsletter. The objective of this study is to evaluate its quality as a digital communication medium, in terms of satisfaction and loyalty to the pregnancy follow-up and delivery service. A cross-sectional, prospective study was carried out, surveying 179 patients by means of an online self-referral questionnaire including variables related to humanization, information needs, perceived accompaniment and satisfaction, as well as factors related to its influence on their decision to remain loyal to the center. A total of 81.2% of the participants showed high levels of satisfaction with the program. Satisfaction among nulliparous patients was significantly lower in several aspects. The resolution of doubts and the perception of peace of mind following the information received was positive for 54.8%. Of the patients in the program, 88.8% finally remained at the center, showing a strong influence of the program on their decision (mean value 75 on 1 to 100 scale). A weekly digital newsletter with specific information reduced the demand for information from pregnant women, generating high levels of satisfaction and positively influencing the decision to remain loyal to the Center.


Physico-chemical modeling of the role of free radicals in photodynamic therapy. IV. Quantitative aspects of photodynamic effects on free radicals generated in cell cultures.
Production and the mechanism of the interactions of free radicals generated by stimulated macrophages in the presence of luminol and a free radical inhibitor was investigated to determine the possibility of using luminol-dependent chemiluminescence for studying photodynamic effects in biology. Earlier measurements have been revisited and additional experiments performed indicating that oxidation products of luminol neither inhibit the in vitro formation of radicals nor quench CL. Simulation based on the mechanism suggested revealed that the likely value for the rate constant of the primary step between luminol and superoxide anion radicals producing luminol radicals is 5x10(2)-1x10(3) M-1s-1. It has been established that the ratio of the concentration of radicals generated by the biological system to that formed by oxidation of luminol exceeds 10(3); that is, the contribution of the latter is negligible and the system is appropriate to measure quantitatively the effect of excited photosensitizers on free radicals.


Culturally Adapting an Internet-Delivered Mindfulness Intervention for Indonesian University Students Experiencing Psychological Distress: Mixed Methods Study.
Psychological distress is prevalent among university students. However, the availability of evidence-based mental health treatment remains limited in many low- and middle-income countries, including Indonesia. Internet-delivered, mindfulness-based interventions that reduce distress have potential for treating university student distress at scale. Unfortunately, evidence-based, internet-delivered mindfulness treatments are not yet available in Indonesia. Cultural adaptation of established evidence-based, internet-delivered mindfulness interventions is needed. In this paper, we describe the process of culturally adapting an Australian internet-delivered mindfulness program (Introduction to Mindfulness) to be relevant and appropriate for treating Indonesian university students' psychological distress. To assist the cultural adaptation process, we used a systematic cultural adaptation framework and a mixed methods approach combining quantitative and qualitative methods. In study 1 (information gathering), we administered an internet-delivered questionnaire to Indonesian university students (n=248) to examine their preferences regarding an internet-delivered mindfulness intervention. In study 2 (preliminary design), a draft program was developed and independently reviewed by Indonesian stakeholders. Stakeholders (n=25) included local Indonesian mindfulness and mental health professionals (n=6) and university students (n=19), who were selected to maximize sample representativeness regarding personal and professional characteristics. To evaluate the initial design and cultural congruence of the internet-delivered mindfulness program in the Indonesian context, we conducted interviews and focus groups with stakeholders. Stakeholders also completed the Cultural Relevance Questionnaire. In study 1, most Indonesian university students (240/248, 96.8%) reported openness to an internet-delivered mindfulness program. Most of interested students (127/240, 52.9%) preferred the length of the program to be 3 to 4 sessions, with 45.8% (110/240) preferring brief lessons taking only 15 to 30 minutes to complete. They (194/240, 80.8%) recommended that the program be accessible both through websites and mobile phones. In study 2, Indonesian stakeholders generally found the internet-delivered program to be highly culturally appropriate in terms of language, concepts, context, treatment goals, and depictions of students' emotional and behavioral experiences. However, stakeholders also recommended some specific adaptations regarding the program's delivery model (eg, combining visual and audio modalities when delivering psychoeducation), cultural components (eg, including more social and spiritual activities), program practicality (eg, including rewards to promote engagement), and design elements (eg, including additional culturally relevant illustrations). Following stakeholder feedback, a new culturally adapted Indonesian internet-delivered mindfulness program called Program Intervensi Mindfulness Daring Mahasiswa Indonesia was created. This study highlights the process and importance of cultural adaptation of an evidence-based mindfulness treatment and demonstrates how this may be achieved for internet-delivered psychotherapy programs. We found that a culturally adapted internet-delivered mindfulness program was relevant for Indonesian students with some adjustments to the programs' content and delivery. Future research is now needed to evaluate the clinical benefit of this program.


Development of attentional networks during childhood and adolescence: A functional MRI study.
Attention ability is one of the most important cognitive functions. It develops mainly during school age. However, the neural basis for the typical development of attentional functions has not been fully investigated. To clarify the development of the aforementioned function and its neural basis, this study examined brain function in children and adolescents during the performance of an attention network test (ANT) using functional magnetic resonance imaging. One hundred and sixty-three volunteers (8-23 years, 80 female) participated in this study. Using a modified version of ANT, we assessed the efficiency of two attentional functions-orienting and executive attention-by measuring how reaction time is affected by spatial cue location and flanker congruency and examined the functional brain areas-attentional networks-associated with two attentional functions. Consistent with the findings of previous studies, the superior parietal lobule, visual association cortex, left precentral gyrus, and supplementary motor area were activated during the orienting attention, while the anterior cingulate cortex, visual association cortex, lateral prefrontal cortex, thalamus, and caudate were activated during the executive attention. Moreover, negative correlations with age were found for activations in the inferior frontal gyrus, dorsomedial prefrontal cortex, and caudate nucleus in the orienting attention, while no correlations with age related to executive attention were found. In conclusion, this study revealed common and distinct features in the neural basis of the attentional functions in children and adolescents compared with that of adults and their developmental changes with age.


Identification of a lower grade muconodular subtype of gastric mucinous cancer.
Until now, survival analysis of gastric mucinous cancers showed either no difference or an even worse prognosis than stage-adjusted non-mucinous tumours. In the pancreas and breast, mucinous cancers showing well-demarcated mucin deposits (muconodular pattern), expansile growth and predominance of MUC2 mucin are known to have a more favourable prognosis. In this study, an attempt was made to separate, among 41 gastric mucinous cancers, a subgroup of tumours with muconodular expansile pattern, possibly predictive of a more favourable outcome. A group of 15 tumours was identified, which were characterised by overwhelming (80-100%) mucinous component, predominance of mucus over tumour cells inside muconodules, moderately aggressive growth of their epithelial component (reduced proliferative rate, moderate anaplasia, lack of angioinvasion and limited lymphoinvasion) and dominant expression of intestinal goblet cell markers, with special reference to MUC2 mucin. Univariate and multivariate survival analysis showed a significantly improved outcome of these lower grade muconodular tumours compared with the remaining mucinous cancers as well as with non-mucinous cancers of cohesive, diffuse (signet-ring cell included) and undifferentiated high-grade types.


Formulation and optimization of dimenhydrinate emulgels for topical delivery using response surface methodology.
Development of dimenhydrinate (DMN) emulgel formulation has been described in this work with enhanced permeation for transdermal delivery of DMN for effective management of motion sickness. Various DMN emulgel formulations were prepared using central composite design in response surface methodology. Propylene glycol and olive oil were used in varying ratios as permeation enhancers along-with carbopol-934 as gelling agent. Prepared formulations were evaluated by physico-chemical properties, stability and Fourier transform infrared spectroscopy (FTIR) studies. In-vitro drug release was studied using cellophane membrane. Formulation F2 showed maximum drug permeation following diffusion-based release mechanism and was used in further studies. Rat skin was used in Franz cell for ex-vivo studies to determine various permeation kinetic parameters. FTIR studies provided no evidence of chemical interaction between DMN and polymers used, whereas molecular docking revealed formation of a stable complex in the presence of aqueous environment with stable intermolecular binding and the complex was well hydrated. No evidence of skin irritation was observed in human volunteers following application of the optimized formulation. Histopathology data of the rat skin showed a decreased proliferation of the lymphocytes whereas monocytes were induced. In conclusion, combination of propylene glycol and olive oil was successfully employed for delivery of DMN through transdermal route with good permeability and prolonged release time that can be highly beneficial in treating motion sickness in unusual circumstances.


New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal.
Various theories try to explain the development and progression of endometriosis, however, no single theory can explain all aspects of this disorder. Gene expression profiling studies might reveal factors that explain variability in disease development and progression, which can serve as specific biomarkers for endometriosis and novel drug development. We have recently showed that the upregulated genes were predominantly clustered in stress and detoxification, providing a mechanistic explanation for the oxidative stress and chronic inflammatory response in endometriosis. This review aims: (1) to analyse the published data, with the aim of identifying pathways consistently regulated by the endometriosis genotype and (2) to summarise the findings of specific genes, which are involved in the process of oxidative stress and inflammation. We identified gene array and proteomics studies whose data were accessible in PubMed. A major finding is the increased expressions of several markers including heat shock protein, S100, fibronectin, and neutrophil elastase, which might be involved in the process of Toll-like receptor (TLR)-dependent sterile inflammation. The study reviews a convergence in the main pathogenic process, where the TLR-mediated inflammation occurs possibly through the endogenous ligands. In conclusion, a circulus vitiosus of both the oxidative stress pathway and the TLR pathways is generated when the process becomes chronic (danger signal spiral).


Bioremediation of pulp and paper mill effluent with Phanerochaete chrysosporium.
The present study reports on the treatment of pulp and paper mill effluent by Phanerochaete chlysosporium and the same has been compared at two different pH, 5.5 and 8.5. At both the pH, colour, COD, lignin content and total phenols of the effluent significantly declined after bioremediation. However, greater decolourisation and reduction in COD, lignin content and total phenols were observed at pH 5.5. Such bioremediated effluent of pulp and paper mill could gainfully be utilized for crop irrigation.


Atrial arrhythmogenesis in obstructive sleep apnea: Therapeutic implications.
The prevalence of sleep disordered breathing like obstructive sleep apnea (OSA) among patients with atrial fibrillation (AF) is 40-50%. OSA reduces success rate of catheter based and pharmacological antiarrhythmic treatment. Additionally, efficient treatment of OSA by continuous positive airway pressure ventilation (CPAP), the first line therapy of OSA, has been shown to improve catheter ablation success rates in AF-patients. A systematic literature search using several databases was performed to review the pathophysiology of obstructive apneas in OSA potentially leading to the development of a substrate for AF and to explain potential mechanisms involved in the clinically observed atrial antiarrhythmic effect of effective CPAP therapy.


A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans.
A mild and general protocol for the Pd(0)-catalyzed heteroannulation of o-bromoanilines and alkynes is described. Application of a Pd(0)/P((t)Bu)3 catalyst system enables the efficient coupling of o-bromoanilines at 60 °C, mitigating deleterious side reactions and enabling access to a broad range of useful unnatural tryptophans. The utility of this new protocol is demonstrated in the highly convergent total synthesis of the bisindole natural product (-)-aspergilazine A.


[A global evaluation of the quality of care in cardiac surgery].
Until now, all reflections about cardiac surgery have been quantitative. Currently, quantitative saturation of cardiac surgery needs in France has been reached or even exceeded in some areas. Consequently, a qualitative approach becomes fundamental: to provide each patient, prior to the operation, with an assessment of his/her vital risk at a specific site; to allow cardiologists to objectively and statistically know the complete results obtained by various surgical teams; to incite improvements among surgical teams; and lastly, to allow the administration to assess services provided to patients. This study concerns 1271 patients consecutively operated on between January 1990 and December 1993 by the very same surgeon and represents the outline of a logical method of controlling clinical results.


LINC00460/DHX9/IGF2BP2 complex promotes colorectal cancer proliferation and metastasis by mediating HMGA1 mRNA stability depending on m6A modification.
Increasing studies have shown that long noncoding RNAs (lncRNAs) are pivotal regulators participating in carcinogenic progression and tumor metastasis in colorectal cancer (CRC). Although lncRNA long intergenic noncoding RNA 460 (LINC00460) has been reported in CRC, the role and molecular mechanism of LINC00460 in CRC progression still requires exploration. The expression levels of LINC00460 were analyzed by using a tissue microarray containing 498 CRC tissues and their corresponding non-tumor adjacent tissues. The correlations between the LINC00460 expression level and clinicopathological features were evaluated. The functional characterization of the role and molecular mechanism of LINC00460 in CRC was investigated through a series of in vitro and in vivo experiments. LINC00460 expression was increased in human CRC, and high LINC00460 expression was correlated with poor five-year overall survival and disease-free survival. LINC00460 overexpression sufficiently induced the epithelial-mesenchymal transition and promoted tumor cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. In addition, LINC00460 enhanced the protein expression of high-mobility group AT-hook 1 (HMGA1) by directly interacting with IGF2BP2 and DHX9 to bind the 3' untranslated region (UTR) of HMGA1 mRNA and increased the stability of HMGA1 mRNA. In addition, the N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC. Finally, it suggested that HMGA1 was essential for LINC00460-induced cell proliferation, migration, and invasion. LINC00460 may be a novel oncogene of CRC through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. LINC00460 can serve as a promising predictive biomarker for the diagnosis and prognosis among patients with CRC.


[Effect of gamma radiation on the concentration of pyruvate and lactate in erythrocytes of healthy men after submaximal physical exercise].
The aim of this work was to study the effect of gamma radiation and submaximal physical exercise on the concentration of final products of anaerobic glycolytic pathway in erythrocytes of healthy men. Twenty one men aged 20-22 were examined. They underwent physical exercise at doses of 2 w/kg body weight for 15 min. Erythrocytes were taken in the rest and after physical exercise and were exposed to gamma radiation (500 Gy doses) from 60Co source. The concentration of pyruvate was estimated by Fermognost tests and the concentration of lactate by Boehringer Mannheim tests. The submaximal physical exercise was found to cause a significantly increased concentration of pyruvate and lactate in the non-radiated and irradiated erythrocytes. Gamma radiation at 500 Gy dose was found to increase concentration of pyruvate in erythrocytes (in the rest and after physical exercise) with simultaneous decrease of lactate concentration.


Differential expression of synapsin in visual neurons of the locust Schistocerca gregaria.
In many taxa, photoreceptors and their second-order neurons operate with graded changes in membrane potential and can release neurotransmitter tonically. A common feature of such neurons in vertebrates is that they have not been found to contain synapsins, a family of proteins that indicate the presence of a reserve pool of synaptic vesicles at synaptic sites. Here, we provide a detailed analysis of synapsin-like immunoreactivity in the compound eye and ocellar photoreceptor cells of the locust Schistocerca gregaria and in some of the second-order neurons. By combining confocal laser scanning microscopy with electron microscopy, we found that photoreceptor cells of both the compound eye and the ocellus lacked synapsin-like immunostaining. In contrast, lamina monopolar cells and large ocellar L interneurons of the lateral ocellus were immunopositive to synapsin. We also identified the output synapses of the photoreceptors and of the L interneurons, and, whereas the photoreceptor synapses lacked immunolabeling, the outputs of the L interneurons were clearly labeled for synapsin. These findings suggest that the photoreceptors and the large second-order neurons of the locust differ in the chemical architecture of their synapses, and we propose that differences in the time course of neurotransmission are the reason for this.


CircularRNA circPARP4 promotes glioblastoma progression through sponging miR-125a-5p and regulating FUT4.
Circular RNA (circRNA) is a widely expressed non-coding RNA element characterized by a covalently closed continuous loop. Emerging evidence suggests important roles of circRNAs in the pathogenesis of human cancers. However, the functions and underlying mechanisms of circRNAs in glioma remain largely unclear. Previously, our studies uncovered a batch of abnormally expressed circRNAs in glioma tissue, among which circPARP4 was significantly upregulated with the top fold change. Here, we focused on the functional investigation toward circPARP4 in glioblastoma progression and looked for insight into its underlying mechanisms. The results confirmed the elevated expression of circPARP4 in glioma and found its association with glioma pathological grade. Gain- and loss-of-function strategies showed that circPARP4 could obviously promote glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistically, in vivo and in vitro studies demonstrated that circPARP4, as a miRNA sponge, directly interacted with miR-125a-5p, which then regulated FUT4 to exert the oncogenic effect on glioma behavior. Our findings illustrate functions of circPARP4 in modulating glioma progression through miR-125a-5p/FUT4 pathway, which provides a novel and potential target for glioma therapy.


Residential facility is "hospital" in group medical policy dispute.
A residential facility that treated preadolescent children suffering from functional nervous disorders was considered to be a "hospital" for purposes of coverage under a group medical insurance policy, despite the fact that it lacked an on-premises surgical facility and did not provide 24-hour nursing services by registered nurses. The insurance company had waived the surgical facility requirement. Additionally, since the policy in question did not contain a definition of "nursing services," there was no requirement that these services be provided 24 hours a day by registered nurses. Thus the insureds were entitled to coverage of the treatment for their son in the residential facility. But a bad faith claim was denied because the insurer's interpretation of its policy was not found to be unreasonable.


Anomalous excitations of atomically crafted quantum magnets.
High-energy resolution spectroscopic studies of quantum magnets proved extremely valuable in accessing magnetodynamics quantities, such as energy barriers, magnetic interactions, and lifetime of excited states. Here, we investigate a previously unexplored flavor of low-energy spin excitations for quantum spins coupled to an electron bath. In sharp contrast to the usual tunneling signature of two steps symmetrically centered around the Fermi level, we find a single step in the conductance. Combining time-dependent and many-body perturbation theories, magnetic field-dependent tunneling spectra are explained as the result of an interplay between weak magnetic anisotropy energy, magnetic interactions, and Stoner-like electron-hole excitations that are strongly dependent on the magnetic states of the nanostructures. The results are rationalized in terms of a noncollinear magnetic ground state and the dominance of ferro- and antiferromagnetic interactions. The atomically crafted nanomagnets offer an appealing model for the exploration of electrically pumped spin systems.