[Dynamic observation of pulmonary ventilation function in workers contacting chromate].
To explore changes of pulmonary ventilation function of chromate exposed workers. Ninety-five chromate exposed workers were used as exposure group, and forty-two workers without chromate exposure as control group. Pulmonary ventilation function was performed two times in the winter of 2010 and 2011 respectively in one chromate manufactured factory in Henan Province. In 2010, pulmonary ventilation function of chromate exposed group compared with the control group, forced vital capacity [FVC, (75.38±15.23) L vs. (83.99±26.52)L], forced expiratory volume in one second [FEV1,(82.13±16.51)L vs.(91.24±30.03)L], FEV1/FVC(112.10±13.23 vs. 116.18±11.32), peak expiratory flow [PEF,(74.31±28.09) L/s vs.(78.13±28.34)L/s], maximal expiratory flow [MEF,(101.23±46.37) L/s vs. (110.02±41.40)L/s], maximum ventilation volume [MVV,(90.82± 16.89)L/min vs. (99.95±22.61)L/min]were significantly decreased(P<0.05). In 2011, pulmonary ventilation function of chromate exposed group compared with the control group, FVC[(72.34±14.18)L vs.(81.01±20.79)L], FEV1[(76.04±16.20)L vs.(86.71±24.53)L], FEV1/FVC(109.10±16.18 vs.114.08±10.79), PEF[(71.35±24.87 )L/s vs.(75.36±20.67)L/s], MEF[(96.51±30.17)L/s vs.(107.11±34.81)L/s], MVV[(84.85±21.22)L/min vs. (96.77±22.63)L/min] were also significantly decreased(P<0.05). 2011 compared with 2010, pulmonary ventilation function of chromate exposed group FEV1[(76.04±16.20)L vs.( 82.13±16.51)L], MEF[(96.51±30.17)L/s vs. (101.23±46.37)L/s], MVV[(84.85±21.22)L/min vs. (90.82±16.89)L/min] were significantly decreased(P<0.05). Comparing the classification and category of pulmonary dysfunction based on FVC, FEV1, FVC/ FEV1, no difference was found for classification between the two groups and the category of pulmonary dysfunction almost belongs to limit type, which did not change with exposed time. Chronic chromate exposure can cause significant effects on pulmonary function of the workers, and the types of work in production can affect the results.


Modulation of the thermoresponsive behavior of poly(N,N-diethylacrylamide) via cyclodextrin host/guest interactions.
The modulation of the cloud point of aqueous poly(N,N-diethylacrylamide) solutions via the formation of supramolecular cyclodextrin complexes with hydrophobic end groups, namely adamantyl, tert-butyl phenyl and azobenzene, synthesized via RAFT polymerization is described. The dependence of the apparent cloud points after cyclodextrin complexation is investigated with respect to the type and quantity of the guest end group, the polymer chain length and the cyclodextrin/end group ratio. Furthermore, the effect is reversed via the addition of guest molecules or via biocompatible enzymatic degradation of the cyclodextrins entire.


Cutaneous metastasis of cecum cancer with MSI-high and BRAFV600E mutation: a case report.
Cutaneous metastases of colorectal cancer (CRC) are rare, occurring in 0.7% to 5% of cancer patients. Furthermore, the molecular subtypes of cutaneous metastasis of CRC are unclear. Here, we present a rare case of cutaneous metastasis of high-frequency microsatellite instability (MSI-high)/BRAFV600E-mutant cecum cancer. A 77-year-old woman presented at the outpatient clinic with a subcutaneous mass on her left back. An excisional biopsy was performed and metastatic cutaneous adenocarcinoma was diagnosed. A computed tomography scan of the thorax and abdomen showed thickening of the cecum wall, the presence of pericolic lymph nodes, multiple masses in the liver, and a single nodule in the right lung. Right colectomy with D2 lymphadenectomy and functional end-to-end anastomosis was performed because of the almost-complete intestinal obstruction. The expression of KRAS wild type, BRAFV600E mutation, and MSI-high was detected in the cecum cancer using molecular pathological examination. She received chemotherapy with XELOX + BEV regimen (capecitabine + oxaliplatin + bevacizumab). After four administrations, a computed tomography scan showed reduction of distant metastases, which suggested partial response. We encountered a rare case of cutaneous metastasis of MSI-high and BRAFV600E-mutant cecum cancer. In the future, it will be necessary to accumulate more cases to identify clinical features and more effective treatments for CRCs with cutaneous metastasis.


The effect of introducing small cavities on the allosteric inhibition of phosphofructokinase from Bacillus stearothermophilus.
The allosteric coupling free energy between ligands fructose-6-phosphate (Fru-6-P) and phospho(enol)pyruvate (PEP) for phosphofructokinase-1 (PFK) from the moderate thermophile, Bacillus stearothermophilus (BsPFK), results from compensating enthalpy and entropy components. In BsPFK the positive coupling free energy that defines inhibition is opposite in sign from the negative enthalpy term and is therefore determined by the larger absolute value of the negative entropy term. Variants of BsPFK were made to determine the effect of adding small cavities to the structure on the allosteric function of the enzyme. The BsPFK Ile → Val (cavity containing) mutants have varied values for the coupling free energy between PEP and Fru-6-P, indicating that the modifications altered the effectiveness of PEP as an inhibitor. Notably, the mutation I153V had a substantial positive impact on the magnitude of inhibition by PEP. Van't Hoff analysis determined that this is the result of decreased entropy-enthalpy compensation with a larger change in the enthalpy term compared to the entropy term.


[Effect of triptolide in improving platelet activation in patients with ankylosing spondylitis by regulating VEGFA,SDF-1,CXCR4 pathway].
The effect of triptolide( TP) on VEGFA,SDF-1,CXCR4 pathway were investigated in vitro to explore the mechanism in improving platelet activation in patients with ankylosing spondylitis( AS). Peripheral blood mononuclear cells( PBMC) were used for the experiment and divided into 4 groups: normal group( NC),model group( MC),triptolide group( TP),and AMD3100 group. The optimal concentration of TP was measured by the MTT method. The expressions of TNF-α,IL-1β,IL-4,IL-10,VEGFA and VEGFR were detected by ELISA. The expressions of SDF-1,CXCR4 and VEGFA were detected by real-time quantitative PCR( RT-qPCR).The expressions of SDF-1,CXCR4,VEGFA and VEGFR were detected by Western blot. The expression levels of CD62 p,CD40 L and PDGFA were detected by immunofluorescence. MTT results showed that medium-dose TP had the strongest inhibitory effect on cells at24 h. The results of ELISA and PCR showed that TP inhibited mRNA expressions of IL-1β,TNF-α,VEGFA,VEGFR and SDF-1,CXCR4 and VEGFA. The results of Western blot indicated that TP inhibited SDF-1,CXCR4 and VEGFA,VEGFR protein expressions; immunofluorescence results indicate that TP can inhibit the expressions of CD62 p,CD40 L,PDGFA. TP may regulate platelet activation by down-regulating SDF-1,CXCR4,VEGFA and VEGFR mRNA expressions,thereby down-regulating IL-1β and TNF-αexpressions,and up-regulating the expressions of IL-4 and IL-10 cytokines.


Inflammatory Bowel Disease in Children.
Crohn's disease and ulcerative colitis remain medically incurable conditions with potentially significant morbidity. The treatment of children with these conditions therefore should seek to reduce or eliminate symptoms, optimize nutritional status, promote normal growth and development, prevent complications, and minimize the potential psychologic effects of chronic illness. Treatment strategies must seek to both induce and maintain clinical remission. For all but the most mildly affected children with Crohn's disease, a combination of nutritional and pharmacologic approaches is optimal. For those with ulcerative colitis, anti-inflammatory medication is necessary. Moderate to severe Crohn's disease acutely responds best to potent immunomodulatory therapy, eg, corticosteroids and infliximab. Either agent must be coupled with 6-mercaptopurine or azathioprine to maintain long-term remission and to minimize toxicity. Particular attention must be paid to limit the growth suppression and other toxic effects of corticosteroids. Elemental or semielemental enteral nutrition also can induce remission effectively, but relapse is common after primary nutritional therapy is discontinued, mandating concomitant pharmacologic therapy with either 6-mercaptopurine or azathioprine. The availability of 6-mercaptopurine/azathioprine metabolite testing allows optimization of immunomodulatory therapy, detection of noncompliance, and avoidance of potentially dangerous toxicity. Mild ulcerative colitis acutely responds to treatment with a 5-aminosalicylate medication. Long-term remission frequently can be maintained with the same medication. Moderate to severe disease activity requires potent immunomodulatory therapy if colectomy is to be avoided. Surgery is a potential cure for patients with ulcerative colitis, although the development of pouchitis after ileal pouch anal anastomosis is common and frequently requires long-term medical management. Surgery provides only palliative relief of complications in those with Crohn's disease. Emerging therapies, especially evolving biologic and probiotic agents, offer hope for better treatments in the years ahead.


The posterior field P of cat auditory cortex: coding of envelope transients.
The posterior field (P) of the cat auditory cortex contains a very high proportion of neurons whose responses change non-monotonically with the sound pressure level (SPL) of tonal stimuli, leading to circumscribed frequency-SPL response areas, and it has therefore been suggested that field P may be specialized for processing of sound intensity. We demonstrate here a great diversity of response areas in field P. Furthermore, by varying tone SPL and rise time, we show that, as in primary auditory cortex (AI), the onset response of a field P neuron is better described as a function of the instantaneous peak pressure (envelope) at the time of response generation than of the steady-state SPL of the stimulus. Such responses could be used to track transients or represent envelopes in more general terms, rather than to code SPL. Compared with AI, field P neurons have relatively long minimum latencies along with a large jitter in spike timing. Tracking would therefore be most effective for slowly varying envelopes, and one function of the inhibition that generates non-monotonicity in field P may be to suppress temporally sluggish responses to rapid transients, such as the onsets of high-SPL, short rise time tones. Field P may thus be specialized for coding slowly varying signals.


T lymphocyte adhesion to human synovial fibroblasts. Role of cytokines and the interaction between intercellular adhesion molecule 1 and CD11a/CD18.
We studied the adhesion of human peripheral blood T lymphocytes to human synovial fibroblasts stimulated with interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), or combinations of these cytokines. T lymphocytes bound poorly to untreated human synovial fibroblasts. IFN gamma treatment resulted in the largest increase in adhesion, followed by TNF alpha and IL-1 beta. Combinations of IFN gamma + TNF alpha and IFN gamma + IL-1 beta had a synergistic effect on intercellular adhesion molecule 1 (ICAM-1) expression and adhesion. The increase in cellular adhesion induced by cytokines correlated with the up-regulation of the number of cells expressing ICAM-1 and the density of antigen/cell. There was no synergistic effect on leukocyte function-associated antigen 3 (LFA-3) or on HLA class I or class II antigen expression. Adhesion was only partially inhibited by anti-ICAM-1, anti-LFA-1, or anti-CD18. These findings suggest the existence of ICAM-1--independent and CD11/CD18-independent adhesion mechanisms. Anti-LFA-3 was completely ineffective as an inhibitor of adhesion. There was no additive or synergistic advantage of using combinations of antibodies to increase the level of inhibition, i.e., anti--ICAM-1 + anti-LFA-3, anti-ICAM-1 + anti-CD18, or anti-ICAM-1 + anti-LFA-1 (CD11a). Our data indicate that proinflammatory cytokines may play a prominent role in the formation and exacerbation of synovial hyperplasia, by regulating the recruitment and retention of T lymphocytes via the up-regulation of adhesion molecules on synovial fibroblasts.


Protein Nutrition and Malnutrition in CKD and ESRD.
Elevated protein catabolism and protein malnutrition are common in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The underlying etiology includes, but is not limited to, metabolic acidosis intestinal dysbiosis; systemic inflammation with activation of complements, endothelin-1 and renin-angiotensin-aldosterone (RAAS) axis; anabolic hormone resistance; energy expenditure elevation; and uremic toxin accumulation. All of these derangements can further worsen kidney function, leading to poor patient outcomes. Many of these CKD-related derangements can be prevented and substantially reversed, representing an area of great potential to improve CKD and ESRD care. This review integrates known information and recent advances in the area of protein nutrition and malnutrition in CKD and ESRD. Management recommendations are summarized. Thorough understanding the pathogenesis and etiology of protein malnutrition in CKD and ESRD patients will undoubtedly facilitate the design and development of more effective strategies to optimize protein nutrition and improve outcomes.


Percutaneous testicular biopsy for indeterminate testicular lesions.
Ultrasound forms an important part of the assessment of the testicle. Nevertheless, there are a number of situations in which clinical and radiological assessment is unable to provide a definitive diagnosis of a testicular lump. In these situations, historically, either open biopsy or orchidectomy has been performed. Ultrasound-guided percutaneous testicular biopsy is an alternative, less invasive method of obtaining histological diagnosis. Here we describe the rationale, technique and potential uses of the technique.


[Amniotic fluid embolism with coagulation disorder--a case report (author's transl)].
A case of amniotic fluid embolism during the delivery of a twin pregnancy is reported. After immediate resuscitation with artificial ventilation the mother and the neonates survived the acute episode. As a result of hyperfibrinolysis with premature separation of the placenta a dramatic postpartum haemorrhage occurred, which could be controlled by Fritsch' manoeuvre. Meanwhile it was possible to restore the coagulation disorder with fresh whole blood, fibrinogen and an antifibrinolytic agent (Aprotinin).


Novel recombinant congenic mouse strain developing arthritis with enthesopathy.
Based on the hypothesis that the complex pathological and immunological manifestations of rheumatoid arthritis (RA) and the related diseases are under the control of multiple gene loci with allelic polymorphism, a recombinant congenic mouse strain was prepared between an MRL/Mp-lpr/lpr (MRL/lpr) strain, which develops arthritis resembling RA, and a non-arthritic strain C3H/HeJ-lpr/lpr (C3H/lpr). In MRL/lpr x (MRL/lpr x C3H/lpr) F1 mice, the mice developing severe arthritis were selected based on joint swelling to further continue intercrosses, and then an McH-lpr/lpr-RA1 (McH/lpr-RA1) strain was established and its histopathological phenotypes of joints and autoimmune traits were analyzed. Arthritis in McH/lpr-RA1 mice developed at a higher incidence by 20 weeks of age, compared with that in the MRL/lpr mice, who had severe synovitis (ankle, 60.3%; knee, 65.1%), and also fibrous and fibrocartilaginous lesions of articular ligamenta resembling enthesopathy (ankle, 79.4%; knee, 38.1%), resulting in ankylosis. The lymphoproliferative disorder was less, and serum levels of IgG and IgG autoantibodies including anti-dsDNA and rheumatoid factor were lower than those of both MRL/lpr and C3H/lpr strains. McH/lpr-RA1 mice may provide a new insight into the study of RA regarding the common genomic spectrum of seronegative RA and enthesopathy.


IL-2 receptor and HLA class II antigens on cerebrospinal fluid cells of patients with multiple sclerosis and other neurological diseases.
The presence of IL-2 receptor and HLA class II antigens as detected by monoclonal antibodies on mononuclear cells from both cerebro-spinal fluid (CSF) and peripheral blood was examined by cytofluorographic analysis in patients with multiple sclerosis (MS) and other neurological diseases. CSF as compared to blood was enriched in cells expressing IL-2 receptor and HLA class II molecules both in MS patients and in other inflammatory diseases of the central nervous system suggesting that activated T-cells concentrate within the central nervous system.


Efficacy and safety of Tian Meng oral liquid for the treatment of insomnia: A protocol for systematic review and meta-analysis.
The incidence of insomnia is very high and seriously affects the lives of its patients. Long-term insomnia can induce other diseases and even cause sudden death. Tian Meng oral liquid is a type of Chinese patent medicine that has been used in the clinical treatment of insomnia and has certain clinical effects. However, its wide application is limited by the lack of evidence-based medical evaluation. Using retrieval strategies, randomized controlled trials on Tian Meng oral liquid for insomnia were obtained from China National Knowledge Infrastructure, WanFang, Chinese Scientific Journals Database PubMed, Embase, and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using RevMan 5.3 and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. This study aims to evaluate the efficacy and safety of Tian Meng oral liquid in the treatment of insomnia and to provide a more reasonable option for clinical medication. Our findings will provide a strong basis for the effectiveness and safety of Tian Meng oral liquid in the treatment of insomnia.


Amino acid concentrations in rumen fluid.
Methods using dialysis or ultrafiltration are described for the collection of extracellular fluid in rumen contents for analysis of amino acids. Marked differences in the concentration of aspartic acid, glutamic acid, and alanine were found in samples of either diffusate or ultrafiltrate and in clarified acidified rumen liquor. Concentrations are given for aspartic acid, glutamic acid, alanine, glycine, gamma-aminobutyric acid, valine, delta-aminovaleric acid, and leucine.


Prognostic significance of pretreatment lymphocyte percentage and age at diagnosis in patients with locally advanced cervical cancer treated with definite radiotherapy.
This study aimed to evaluate the prognostic impact of age at diagnosis, and pretreatment hematologic markers, including lymphocyte percentage and the neutrophil-to-lymphocyte ratio (NLR), in patients with locally advanced cervical cancer (LACC) treated with definitive radiotherapy (RT). A total of 392 patients with LACC (stage IIb to IVa) treated with cisplatin-based concurrent chemoradiotherapy or RT alone between 2001 and 2012 were retrospectively enrolled. Clinical data and pretreatment complete blood counts were extracted from electronic medical records of the patients, and analyzed. Treatment outcomes, progression-free survival (PFS), and overall survival (OS) were evaluated. Low lymphocyte percentage and a high NLR were associated with younger age, advanced stage, larger tumor size, lymph nodes metastasis, and treatment failure. The cut-off value for lymphocyte percentage and NLR was determined using a receiver operating characteristic curve. In univariate analysis, low lymphocyte percentage (≤24%) was associated with poor PFS and OS, while high NLR (>2.8) was significantly associated only with PFS. In multivariate analysis, both lymphocyte percentage (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40-0.85; P=0.005) and NLR (HR, 1.55; 95% CI, 1.07-2.25; P=0.022) had independent prognostic value for PFS. Compared to younger patients (age ≤50 years), older patients (age >60 years) had a lower risk of death. Although the lymphocyte percentage did not remain significant in multivariate analysis for OS, it was predictive of PFS and OS. Thus, lymphocyte percentage is a simple hematologic parameter with a significant prognostic value in patients with LACC treated with definitive RT.


Effective tumor treatment by VEGF siRNA complexed with hydrophobic poly(amino acid)-modified polyethylenimine.
Two copolymers are designed and synthesised for siRNA delivery based on polyethylenimine by grafting hydrophilic acrylamide segments and hydrophobic poly(γ-benzyl L-glutamate). The amphiphilic PEI-PBLG/siRNA complex demonstrates high gene silencing efficiency in the absence or presence of 10 vol% and 50 vol% sera in vitro. The anti-tumor effects in vivo are evaluated in luciferase-bearing mice expressing CT26 tumors. PEI-PBLG/siVEGF complex provides a higher and more sustained suppressive effect by reducing VEGF mRNA expression in the tumors, leading to higher tumor growth inhibition efficacy. Further studies on the potential use of the PEI-PBLG carrier system in mediating the silencing of genes other than VEGF or in other tumor models are recommended.


Should a detailed ultrasound examination of the complete urinary tract be routinely performed in women with suspected pelvic endometriosis?
Is there any benefit to including the routine examination by ultrasound of the bladder, ureters and kidneys of women with endometriosis? The benefit of examination of the complete urinary tract of women with suspected endometriosis is that ureteric endometriosis, with or without hydronephrosis, can be detected which facilitates early intervention to prevent nephropathy. Women with endometriosis can get ureteric obstruction but there is no clear consensus on the correct diagnostic technique. Ultrasound is accurate at detecting women with bladder endometriosis but ureteric involvement has not been assessed previously. This was a prospective observational study, conducted at a teaching hospital over a period of 14 months. A total of 848 women presenting with chronic pelvic pain were included into the study. All women with chronic pelvic pain underwent a detailed transvaginal and transabdominal pelvic ultrasound examination to investigate possible causes of their symptoms. This included a systematic assessment of the urinary bladder, pelvic sections of the ureters and kidneys. The ultrasound findings were compared with findings at surgery and the results of targeted urological imaging and interventions. A total of 848 women presenting with chronic pelvic pain were included into the study. 28/848 women (3.3% 95% CI 2.1-4.5) had evidence of urinary tract abnormalities on initial ultrasound scan. Among these 17/848 (2.0% 95% CI 1.06-2.94) had evidence of urinary tract endometriosis, whilst 11/848 (1.3% 95% CI 0.54-2.06) women had other urinary tract abnormalities. Among women with urinary tract endometriosis 11/17 (65%) had evidence of ureteric involvement, 3/17 (18%) had both ureteric and bladder disease and 3/17 (18%) had bladder disease only. 12/17 (59%) women with urinary tract endometriosis also had evidence of hydronephrosis. The diagnosis of ureteral endometriosis had a sensitivity of 12/13 (92%) (95% CI 63.9-99.8), specificity 151/151 100% (95% CI 97.6-100), PPV 100% (95% CI 73.5-100), NPV 99.3% (95% CI 96.3-99.9%) LR- 0.08 (95% CI 0.01-0.39). The routine examination of the complete urinary tract including the distal ureters is a novel technique that should be evaluated in different populations. Ultrasound is an accurate test to diagnose urinary tract involvement in women with suspected pelvic endometriosis and examination of the complete urinary tract should become an integral part of ultrasound assessment of women with suspected endometriosis.


Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients.
Upshaw-Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura (TTP) due to mutations in the gene that encodes for ADAMTS13 (ADAMTS13), but its clinical signs may be mild or absent during childhood. We have identified 37 patients with USS (24 females, 13 males) belonging to 32 families. The nine women from six families who were diagnosed during their first pregnancy are the focus of this report. Six of the nine women had episodes of thrombocytopenia during childhood misdiagnosed as idiopathic thrombocytopenic purpura. Thrombocytopenia occurred during the second-third trimesters in each of their 15 pregnancies, with 16 babies (one twin pregnancy), often followed by TTP. Of 15 pregnancies, eight babies were stillborn or died soon after birth, and the remaining seven were all premature except one, who was born naturally following plasma infusions to the mother that had started at 8 weeks' gestation. All nine USS women had severely deficient ADAMTS13 activity. ADAMTS13 analyses demonstrated that eight women were compound heterozygotes of Y304C/G525D (2 siblings), R125VfsX6/Q1302X (2 siblings), R193W/R349C (2 siblings), I178T/Q929X, and R193W/A606P; one woman was homozygous for R193W. Only the R193W mutation has been previously reported. These observations emphasize the importance of measuring ADAMTS13 activity in the evaluation of thrombocytopenia during childhood and pregnancy.


Effects of isotretinoin on the olfactory function in patients with acne.
Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell.


Alarm reaction of the top smelt, Atherinops affinis: reexamination.
We did not observe the reported alarm reaction of the top smelt Atherinops affinis (Ayres) when presented with a methanol extract of whole top smelt; we interpret the reaction as an experimental artifact. Rather, a methanol extract of top smelt is an attractant, as is methanol extract of shrimp.


Plant speciation in continental island floras as exemplified by Nigella in the Aegean Archipelago.
Continental shelf island systems, created by rising sea levels, provide a premier setting for studying the effects of geographical isolation on non-adaptive radiation and allopatric speciation brought about by genetic drift. The Aegean Archipelago forms a highly fragmented complex of mostly continental shelf islands that have become disconnected from each other and the mainland in relatively recent geological times (ca <5.2 Ma). These ecologically fairly homogenous islands thus provide a suitable biogeographic context for assessing the relative influences of past range fragmentation, colonization, gene flow and drift on taxon diversification. Indeed, recent molecular biogeographic studies on the Aegean Nigella arvensis complex, combining phylogenetic, phylogeographic and population level approaches, exemplify the importance of allopatry and genetic drift coupled with restricted gene flow in driving plant speciation in this continental archipelago at different temporal and spatial scales. While the recent (Late Pleistocene) radiation of Aegean Nigella, as well as possible instances of incipient speciation (in the Cyclades), is shown to be strongly conditioned by (palaeo)geographic factors (including changes in sea level), shifts in breeding system (selfing) and associated isolating mechanisms have also contributed to this radiation. By contrast, founder event speciation has probably played only a minor role, perhaps reflecting a migratory situation typical for continental archipelagos characterized by niche pre-emption because of a long established resident flora. Overall, surveys of neutral molecular markers in Aegean Nigella have so far revealed population genetic processes that conform remarkably well to predictions raised by genetic drift theory. The challenge is now to gain more direct insights into the relative importance of the role of genetic drift, as opposed to natural selection, in the phenotypic and reproductive divergence among these Aegean plant species.


Research on automatic classification and detection of chicken parts based on deep learning algorithm.
Accurate classification and identification of chicken parts are critical to improve the productivity and processing speed in poultry processing plants. However, the overlapping of chicken parts has an impact on the effectiveness of the identification process. To solve this issue, this study proposed a real-time classification and detection method for chicken parts, utilizing YOLOV4 deep learning. The method can identify segmented chicken parts on the assembly line in real time and accurately, thus improving the efficiency of poultry processing. First, 600 images containing multiple chicken part samples were collected to build a chicken part dataset after using the image broadening technique, and then the dataset was divided according to the 6:2:2 division principle, with 1200 images as the training set, 400 images as the test set, and 400 images as the validation set. Second, we utilized the single-stage target detector YOLO to predict and calculate the chicken part images, obtaining the categories and positions of the chicken leg, chicken wing, and chicken breast in the image. This allowed us to achieve real-time classification and detection of chicken parts. This approach enabled real-time and efficient classification and detection of chicken parts. Finally, the mean average precision (mAP) and the processing time per image were utilized as key metrics to evaluate the effectiveness of the model. In addition, four other target detection algorithms were introduced for comparison with YOLOV4-CSPDarknet53 in this study, which include YOLOV3-Darknet53, YOLOV3-MobileNetv3, SSD-MobileNetv3, and SSD-VGG16. A comprehensive comparison test was conducted to assess the classification and detection performance of these models for chicken parts. Finally, for the chicken part dataset, the mAP of the YOLOV4-CSPDarknet53 model was 98.86% on a single image with an inference speed of 22.2 ms, which was higher than the other four models of YOLOV3-Darknet53, YOLOV3-MobileNetv3, SSD-MobileNetv3, and SSD-VGG16 mAP by 3.27%, 3.78%, 6.91%, and 6.13%, respectively. The average detection time was reduced by 13, 1.9, 6.2, and 20.3 ms, respectively. In summary, the chicken part classification and detection method proposed in this study offers numerous benefits, including the ability to detect multiple chicken parts simultaneously, as well as delivering high levels of accuracy and speed. Furthermore, this approach effectively addresses the issue of accurately identifying individual chicken parts in the presence of occlusion, thereby reducing waste on the assembly line. PRACTICAL APPLICATION: The aim of this study is to offer visual technical assistance in minimizing wastage and resource depletion during the sorting and cutting of chicken parts in poultry production and processing facilities. Furthermore, considering the diverse demands and preferences regarding chicken parts, this research can facilitate product processing that caters specifically to consumer preferences.


[Simulation Analysis of the Impact of COVID-19 Pandemic Control on Air Quality in Henan Province based on Machine Learning Algorithm].
To reduce the risks of COVID-19 on society and the health of the general public, necessary prevention and control measures were implemented throughout China in 2020. Consequently, air quality was greatly improved due to lower emissions. However, the improvement of air quality could also be closely related to meteorological conditions. During quarantine (January 27 to February, 2020), reductions were observed in the concentration of all air pollutants in Henan Province (PM2.5, PM10, SO2, CO, and NO2 decreased by 36.89%, 34.18%, 19.43%, 29.85%, and 58.51%, respectively) relative to measurements taken from January 1 to 26, 2020. The only exception was for the concentration of O3, which increased by 69.64%. This study evaluates the importance of meteorological conditions in air pollution, through simulation with a long-and-short-term memory network (LSTM) and a machine learning algorithm. Results show that meteorological conditions play a crucial role in air pollutant formation. Given favorable meteorological factors, the concentrations of pollutants could be reduced by 15%-30%, while the reduction due to anthropogenic emission control ranges from 6%-40%. During the epidemic, meteorological conditions and human emissions accounted for 34.84% and 34.81% of the increase in O3 concentration, respectively. The results show that primary pollutant concentrations are more sensitive to the intensity of anthropogenic emissions. However, secondary pollutants are more dependent on meteorological factors. Furthermore, a nonlinear relationship has been identified between O3 concentration and to emission intensity. Further investigation into the causes of the rise in O3 concentration is necessary to gain a greater understanding and better control of particulate matter and O3 pollution.


Effects of recombinant human interferons on rheumatoid arthritis B lymphocytes activated by Epstein-Barr virus.
We evaluated the effects of all 3 classes of recombinant human interferon (IFN) on Epstein-Barr virus (EBV) infection of purified B lymphocytes from patients with rheumatoid arthritis (RA). After EBV infection, RA B cells secreted more IgM and significantly more IgM rheumatoid factor (RF) than normals. Spontaneous (no EBV) proliferation, IgM, and IgM RF were also higher in RA. All 3 types of IFN inhibited dose dependently EBV induced B cell activation. In RA, however, higher doses of each class of IFN were necessary to obtain 50% inhibition. IFN gamma was most potent in normals and RA. Four IgM RF production IFN gamma was significantly more potent than IFN alpha and IFN beta in reducing the spontaneous activation of RA B cells, and a similar trend was seen in B cell proliferation. These findings are discussed in the context of ongoing clinical trials with IFN gamma in RA.


Transvenous electrical cardioversion of equine atrial fibrillation: technical considerations.
Conventional treatment of equine atrial fibrillation (AF) involves administration of quinidine salts. Most uncomplicated cases respond to treatment, but pharmacologic cardioversion involves a range of adverse effects, and some horses are unable to tolerate medication. A study was undertaken to develop transvenous electrical cardioversion (TVEC) as an alternative treatment. Safety issues and catheter placement techniques with catheter-integrated cardioversion electrodes were investigated, and responses to shock application were evaluated. After the premortem catheterization of elective-euthanasia horses, no tissue abnormalities were detected at postmortem examination. To evaluate the response to the application of shocks and appropriate electrode positions, an electrical cardioversion of research horses in chronic AF was then attempted. After catheterization of the right atrium (RA) and pulmonary artery through the right jugular vein, horses were placed under general anesthesia. Biphasic, truncated exponential shock waves were delivered at incremental energies until cardioversion was achieved or until a maximum energy of 300 J was reached. Five treatment events were applied to 3 horses, with cardioversion achieved in one of the treatment events. No adverse effects of cardioversion attempts or general anesthesia were observed. The procedure was then applied to 8 client-owned horses, with cardioversion achieved in 7. No adverse responses to appropriately delivered shocks were observed. No antiarrhythmic medications were administered to any horse at any stage. Catheter design and placement technique evolved throughout the study, with combined ultrasonography and pressure guidance proving most effective in achieving appropriate electrode placement. Results suggest TVEC, as applied in the present study, is a safe, effective, and realistic therapeutic option for equine AF.


[Antiviral action of swine leukocyte interferon in mouse experiments].
Swine leukocytes had previously been found to produce interferon which has an antiviral effect not only in swine cells but also in human cells. Preliminary experiments in tissue cultures showed the culture of primarily trypsinized mouse embryo fibroblasts to be as sensitive to swine interferon as human diploid cells. The experiment studying the antiviral effect of swine leukocyte interferon in the animals demonstrated it to protect mice against the pathogenic A/Aishi/68 (H3N2) strain; with a reduction of virus doses to 10 the protective effect of swine interferon increased 2-fold as compared with the experiments using 100-1000 virus doses. Inhibition of virus reproduction in lung tissues of experimental mice inoculated with A/Moscow/23/78 (H1N1), A/Wisconsin/19/67 (Hsw1N1) and A/Aishi/68 (H3N2) strains as compared with the controls. The experimental results suggest that the swine interferon produces the antiviral effect both in tissue culture and experimental animals.


Crystal structure of a type-II cohesin module from the Bacteroides cellulosolvens cellulosome reveals novel and distinctive secondary structural elements.
The incorporation of enzymes into the multi-enzyme cellulosome complex and its anchoring to the bacterial cell surface are dictated by a set of binding interactions between two complementary protein modules: the cohesin and the dockerin. In this work, the X-ray crystal structure of a type-II cohesin from scaffoldin A of Bacteroides cellulosolvens has been determined to a resolution of 1.6 angstroms using molecular replacement. The type-II B. cellulosolvens cohesin (Bc-cohesin-II) is the first detailed description of a crystal structure for a type-II cohesin, and its features were compared with the known type-I cohesins from Clostridium thermocellum and Clostridium cellulolyticum (Ct-cohesin-I and Cc-cohesin-I, respectively). The overall jelly-roll topology of the type-II Bc-cohesin is very similar to that observed for the type-I cohesins with three additional secondary structures: an alpha-helix and two "beta-flaps" that disrupt the normal course of a beta-strand. In addition, beta-strand 5 is elevated by approximately 4 angstroms on the surface of the molecule, relative to the type-I Ct and Cc-cohesins. Like its type-I analogue, the hydrophobic/aromatic core of Bc-cohesin-II comprises an upper and lower core, but an additional aromatic patch and conserved tryptophan at the crown of the molecule serves to stabilize the alpha-helix of the type-II cohesin. Comparison of Bc-cohesin-II with the known type-I cohesin-dockerin heterodimer suggests that each of the additional secondary structural elements assumes a flanking position relative to the putative dockerin-binding surface. The raised ridge formed by beta-strand 5 confers additional distinctive topographic features to the proposed binding interface that collectively distinguish between the type-II and type-I cohesins.


Candida albicans endocarditis with giant vegetation from an implantable cardioverter-defibrillator lead.
Endocarditis is a potentially lethal complication of implantation of a cardioverter-defibrillator (ICD). We report the case of a 62-year-old male with candidemia and vegetation from a large implantable ICD lead that could not be extracted percutaneously. The ICD system was completely and successfully removed through pocket re-exploration and sternotomy with cardiopulmonary bypass. Although the patient was considered at high risk from thrombocytopenia, systemic infection, and symptomatic heart failure with a very low ejection fraction, the surgical procedure used to remove his ICD provided a good clinical outcome. An early and aggressive combination of surgical and medical therapy is effective for the removal of an ICD causing endocarditis, and reimplantation of the device is safe when guided by principles for preventing infection.


Differences of Eu(III) and Cm(III) chemistry in ionic liquids: investigations by TRLFS.
In this study the coordination structure and chemistry of Eu(III) and Cm(III) in the ionic liquid C(4)mimTf(2)N (1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) was investigated by time-resolved laser fluorescence spectroscopy (TRLFS). The dissolution of 1 x 10(-2) M Eu(CF(3)SO(3))(3) and 1 x 10(-7) M Cm(ClO(4))(3) in C(4)mimTf(2)N leads to the formation of two species for each cation with fluorescence emission lifetimes of 2.5 +/- 0.2 ms and 1.0 +/- 0.3 ms for the Eu-species and 1.0 +/- 0.3 ms and 300.0 +/- 50 micros for the Cm-species. The interpretation of the TRLFS data indicates a comparable coordination for both the lanthanide and actinide cation in this ionic liquid. The quenching influence of Cu(II) on the fluorescence emission of Eu(III) and Cm(III) was also measured by TRLFS. While Cu(ii) does not quench the Cm(III) fluorescence emission in C(4)mimTf(2)N the Eu(III) fluorescence emission lifetime for both Eu-species in C(4)mimTf(2)N decreases with increasing Cu(II) concentration. Stern-Volmer constants were calculated (k(SV) = 1.54 x 10(6) M(-1) s(-1) and k(SV) = 2.70 x 10(6) M(-1)). By contrast, the interaction of Cu(II) with Eu(III) and Cm(III) in water leads to a quenching of both the lanthanide and actinide fluorescence. The calculated Stern-Volmer constants are 1.20 x 10(4) M(-1) s(-1) for Eu(III) and 1.27 x 10(4) M(-1) s(-1) for Cm(III). The investigations show, while the chemistry of trivalent lanthanides and actinides is similar in an aqueous system it is dramatically different in ionic liquids. This difference in chemical behavior may provide the opportunity for a separation of lanthanides and actinides with regard to the reprocessing of nuclear fuel.


Promoter and Terminator Discovery and Engineering.
Control of gene expression is crucial to optimize metabolic pathways and synthetic gene networks. Promoters and terminators are stretches of DNA upstream and downstream (respectively) of genes that control both the rate at which the gene is transcribed and the rate at which mRNA is degraded. As a result, both of these elements control net protein expression from a synthetic construct. Thus, it is highly important to discover and engineer promoters and terminators with desired characteristics. This chapter highlights various approaches taken to catalogue these important synthetic elements. Specifically, early strategies have focused largely on semi-rational techniques such as saturation mutagenesis to diversify native promoters and terminators. Next, in an effort to reduce the length of the synthetic biology design cycle, efforts in the field have turned towards the rational design of synthetic promoters and terminators. In this vein, we cover recently developed methods such as hybrid engineering, high throughput characterization, and thermodynamic modeling which allow finer control in the rational design of novel promoters and terminators. Emphasis is placed on the methodologies used and this chapter showcases the utility of these methods across multiple host organisms.


Plasma and platelet concentration and platelet uptake of serotonin in normal and pre-eclamptic pregnancies.
Pharmacologic and methodologic advances over the last decade have resulted in a body of information implicating serotonin as a mediator in the genesis of pre-eclamptic hypertension. Platelets contain the largest storage of serotonin in peripheral blood and have the ability to take up this amine from surroundings, store and release it by several mechanisms. Plasma and platelet serotonin concentrations and platelet serotonin uptake have been measured in 8 non-pregnant women, 12 normal pregnant women and 8 women with severe pre-eclampsia. Plasma serotonin concentration was significantly higher in severely preeclamptic women, compared with age and gestation matched normal pregnant women. In addition, plasma serotonin concentration was directly related to systolic and diastolic blood pressure with severity of the syndrome. Furthermore, platelet serotonin concentration in women with pre-eclampsia was significantly higher than in non-pregnant controls, but it was not significantly different from the normal pregnant women. Moreover, serotonin is effectively taken up by platelets through a saturable transport process. The calculated apparent Km for serotonin uptake process did not differ significantly among non-pregnant women, normal pregnant women and women with pre-eclampsia. However, Vmax values were significantly higher in women with pre-eclampsia than in the normotensive pregnant women. As the actions of serotonin in the periphery could be terminated primarily by active uptake system by platelets and placenta, significant alterations in the rate of transport could result in physiologically significant changes in serotonin levels. These data raise the possibility that abnormal regulation of transporter function is involved in the etiology of pre-eclampsia.


Limitations in equivalence of alternate subtests for Russell's Revision of the Wechsler Memory Scale: causes and solutions.
Reasons for limited equivalence of Form II of the Wechsler Memory Scale (WMS-II) Figural Memory Subtest as an alternate form for the Russell's Revision of the Wechsler Memory Scale (RWMS) Figural Memory Subtest were investigated. Thirty college students rated figural stimuli from RWMS and WMS-II on dimensions related to memory. Raters judged figural stimuli from RWMS to be less memorable, more complex, and more difficult to label verbally. Forms can be made more equivalent by either changes in scoring or the interchanging of stimuli across forms.


Antiestrogen therapy of breast cancer.
Studies in vitro and in animal models have helped define the mechanism of action of antiestrogens and the differences in the physical properties of the various antiestrogens. Tamoxifen is the most widely studied antiestrogen. A review of 45 separate studies has shown a response rate to tamoxifen in advanced breast cancer that varies between 14% and 57%, with an overall response rate of 34%; prior therapy strongly influenced response rate. Menopausal status did not seem to influence response, and no dose-response relationship has been documented. Patients with estrogen-receptor-positive tumors are more likely to respond than those with estrogen-receptor-negative disease. Tamoxifen has been shown to be an unusually safe and well-tolerated drug. Studies of antiestrogens as adjuvants to local therapy of early breast cancer have generally produced encouraging results. More studies are needed, however, in order to define those subsets of patients who are most likely to benefit from adjuvant therapy with tamoxifen and to determine the most effective regimens.


Wrestling with uncertainty after mild traumatic brain injury: a mixed methods study.
Purpose: Our objective was to explore the intersection between mild traumatic brain injury (MTBI) recovery experiences and injury understandings, using both quantitative and qualitative methods.Materials and Methods: The quantitative component was a descriptive case-control study comparing participants (n = 76) who had recovered or not recovered after an MTBI, across demographic and psychological variables. A subset of participants (n = 10) participated in a semi-structured interview to explore experiences of recovery in more detail. We followed threads across the datasets to integrate findings from component methods.Results: The quantitative analyses revealed differences between the two groups in terms of injury recovery understandings and expectations. The qualitative analyses suggested that achieving consistency across information sources was important. By tracing threads back and forth between the component datasets, we identified a super-ordinate meta-theme that captured participants' experiences of wrestling with uncertainty about their recovery and the impacts in terms of heightened anxiety, confusion, and feelings of invalidation.Conclusion: The effectiveness of psychoeducation and reassurance after MTBI may be optimized when content is tailored to the individual. Clinicians are urged to attend both to the subjective interpretations patients make of information gained from formal and informal, internal and external sources, and where information across these sources conflicts and creates uncertainty.Implications for rehabilitationEffectiveness of psychoeducation and reassurance after injury may be optimized when content is tailored to the individual rather than being generic.Effectiveness of such interventions may also be optimized by understanding the subjective interpretations individuals make of injury knowledge gleaned from formal and informal, internal and external sources.Conflicting information from such multiple sources may create uncertainty with associated increased distress as an individual negotiates their recovery from injury. Attending to this uncertainty may be a helpful target for treatment.


Methods for the Comparison of Differential Item Functioning across Assessments.
An important aspect of the educational and psychological evaluation of individuals is the selection of scales with appropriate evidence of reliability and validity for inferences and uses of the scores for the population of interest. One key aspect of validity is the degree to which a scale fairly assesses the construct(s) of interest for members of different subgroups within the population. Typically, this issue is addressed statistically through assessment of differential item functioning (DIF) of individual items, or differential test functioning (DTF) of sets of items within the same measure. When selecting an assessment to use for a given application (e.g., measuring intelligence), or which form of an assessment to use for a test administration, researchers need to consider the extent to which the scales work with all members of the population. Little research has examined methods for comparing the amount or magnitude of DIF/DTF present in two or more assessments when deciding which assessment to use. The current study made use of 7 different statistics for this purpose, in the context of intelligence testing. Results demonstrate that by using a variety of effect sizes, the researcher can gain insights into not only which scales may contain the least amount of DTF, but also how they differ with regard to the way in which the DTF manifests itself.


A dynamic ancestral graph model and GPU-based simulation of a community based on metagenomic sampling.
In this paper, we present an ancestral graph model of the evolution of a guild in an ecological community. The model is based on a metagenomic sampling design in that a random sample is taken at the community, as opposed the taxon, level and species are discovered by genetic sequencing. The specific implementation of the model envisions an ecological guild that was founded by colonization at some point in the past that then potentially undergoes diversification by natural selection. Within the graph, species emerge and evolve through the diversification process and their densities in the graph are dynamic and governed by both ecological drift and random genetic drift, as well as differential viability. We employ the 3% sequence divergence rule at a marker locus to identify operational taxonomic units. We then explore approaches to see whether there are indirect signals of the diversification process, including population genetic and ecological approaches. In terms of population genetics, we study the joint site frequency spectrum of OTUs, as well its associated statistics. In terms of ecology, we study the species (or OTU) abundance distribution. For both, we observe deviations from neutrality, which indicates that there may be signals of diversifying selection in metagenomic studies under certain conditions. The model is available as a GPU-based computer program in C/C++ and using OpenCL, with the long-term goal of adding functionality iteratively to model large-scale eco-evolutionary processes for metagenomic data.


Edendale Hospital, Pietermaritzburg. The first twenty-one years.
Edendale Hospital celebrates its twenty-first anniversary in 1975. Among non-teaching hospitals it has led the field in training and advancement of Black nurses and it has pioneered the employment of full-time specialists. It claims to have the first intensive care unit, the first central sterilising department, and the first postoperative recovery room in Southern Africa. Aspects of Edendale's early history are recorded.


Colloidal gold markers and probes for routine application in microscopy.
Colloidal gold can be used as an electron-dense cytochemical probe for direct or indirect labelling techniques. Gold markers can be prepared in a size range of 5-150 nm, and show size-dependent shape characteristics and absorption spectra. Size and shape distribution increases with mean particle diameter, with appreciable overlapping between populations of different mean size. Using radio isotope-binding assays, spectrophotometric analysis and an innovative rapid microtitration technique, the effect of pH, ionic strength and protein concentration on gold-protein interaction has been studied. Efficient adsorption of protein to gold occurs at, or near, the pI of the protein. The amount of protein needed to effect stabilization is both a function of pH and of ionic strength, but does not reflect the amount of protein binding for all proteins. There is evidence for multilamellar adsorption of proteins to gold, which is discussed in context of the bioactivity, and stability of the probe. A working protocol for the routine reproducible manufacture of protein-gold probes is given, making use of the microtitration assay.


Monoclonals and allergy. A review, with experimental contribution.
The role of monoclonal antibodies in allergy has been explored. First the status of art of monoclonal research in general is reviewed, by outlining a monoclonals identikit and the relevant technologies employed for their development. The attention is then focused on the present impact of monoclonals in the allergological field, first considering a general outline, and then the important steps of standardization of monoclonal antibodies. A comprehensive hint is made concerning the monitoring of immunotherapy, with future extrapolations on developing anti-idiotype vaccines, of which same examples can already be found in the infectious field, thus leaving the way open in allergy as well. A second section deals with the experimental contribution of the Authors, with the description of the preparation of the allergenic extracts of D.F., with details of the relevant steps (rabbit immunization; extract characterization; techniques used for monoclonal screening and characterization). The results obtained are discussed in relation to the techniques employed, weighing the reciprocal advantages and drawbacks.


A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis.
Metabonomic/metabolomic studies can involve the analysis of large numbers of samples for the detection of biomarkers and confidence in the analytical data, generated by methods such as GC and HPLC-MS, requires active measures on the part of the analyst. However, quality control for complex multi-component samples such as biofluids, where many of the components of interest in the sample are unknown prior to analysis, poses significant problems. Here the repeat analysis of a pooled sample throughout the run, thereby enabling the analysis to be monitored and controlled using targeted inspection of the data and pattern recognition, is advocated as a pragmatic solution to this problem.


Microtechnology: meet neurobiology.
The field of neuroscience has always been attractive to engineers. Neurons and their connections, like tiny circuit elements, process and transmit information in a dramatic way that is intimately curious to researchers in the computer science and engineering fields. Of particular interest has been the recent push in applying microtechnology to the field of neuroscience. This review is meant to provide an overview of some of the subtle nuances of the nervous system and outline recent advances in lab on a chip applications in neurobiology. It also aims to highlight some of the challenges the field faces in the hopes of encouraging new engineering researchers to collaborate with neurobiologists to help advance our basic understanding of the nervous system and create novel applications based on neuroengineering principles.


Natural soluble epoxide hydrolase inhibitors from Inula helenium and their interactions with soluble epoxide hydrolase.
The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium were isolated to obtain eight compounds, including 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC50) from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. The inhibition kinetics suggested that 4H-tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constant (Ki) values of 7.02 and 6.57 μM, respectively, and linoleic acid (3) was a competitive type inhibitor with a Ki values of 3.52 μM. The potential interactions of 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524.


Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors.
Skp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 36/64 (56.3%) of non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting molecules including a natural compound 6-O-angeloylplenolin (6-OAP). 6-OAP bound Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and β-TRCP, and accumulation of their substrates Cyclin B1, P27 and E-Cadherin. 6-OAP induced prometaphase arrest and exerted potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and Skp1 inhibitor inactivates crucial oncogenic E3 ligases and exhibits significant therapeutic potentials.


Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress.
Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress.


Semicrystalline Polymer Binary-Phase Structure Templated Quasi-Block Graft Copolymers.
Herein, we report a simple strategy to synthesize quasi-block graft copolymers using the binary phase structure of semicrystalline polymers as the template. An unsaturated ionic liquid, 1-vinyl-3-butylimidazolium bis (trifluoromethylsulfonyl) imide ([VBIm] [TFSI]), is thermodynamically miscible with poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-co-HFP)) in solution. The solidification of P(VDF-co-HFP)/[VBIm] [TFSI] blend leads to the expelling of ILs from the crystalline region and the ILs are only located in the amorphous region. The electron-beam irradiation (EBI) at the solid state of the blends results in the locally grafting of the ILs onto the polymer blocks in the amorphous region, while the EBI does not affect the chemical structure of the crystalline region. Therefore, the quasi-block graft copolymers were achieved with IL-grafted blocks segregated by the unmodified blocks. The achieved block copolymers can be microphase separated into the various nanostructures, as the block copolymers with well-defined structure, upon varying the grafting ratios. The microphase separated quasi-block grafted copolymers exhibit excellent mechanical properties and good electrical properties. The elongation at break is 480% and the stress at break is as high as 30 MPa for the sample with the lamellar-like structure having the grafting ratio of 45.4 wt%.


Comparison of forgiveness and anger-reduction group treatments: a randomized controlled trial.
Interventions to promote forgiveness are effective. However, in what ways and in comparison to what other treatments is still unresolved. College students (n=112) who had been hurt in the past and struggled to overcome their negative experiences of it participated in this study. They were randomly assigned to one of two treatments, one focused on promoting forgiveness and one focused on reducing anger for past hurts, or a waiting list control. Treatment consisted of six 90-minute sessions held in small groups led by one facilitator over the course of 3 weeks. Results of three-level (time within participants within groups) hierarchical linear modeling indicated that the forgiveness treatment (n=41) resulted in greater reductions in hostility and psychological symptoms and more empathy for the offender than the alternative treatment (n=39) and the waitlist (n=32). Participants in both treatment conditions reported greater reductions in desires for revenge than those in the waitlist condition. All participants reported a significant reduction in rumination about the offense. Clinical significance testing mirrored these results. These findings support forgiveness-promoting treatments as effective for reducing psychological symptoms and achieving forgiveness, and suggest that they may be more effective than other types of treatments.


Folic acid decorated chitosan-coated solid lipid nanoparticles for the oral treatment of rheumatoid arthritis.
Background: Systemic treatment of rheumatoid arthritis has been accompanied with several side effects. This study attempts to reduce leflunomide systemic side effects besides increasing its joint healing outcomes via formulation of layer-by-layer coated, leflunomide-loaded solid lipid nanoparticles (SLNs). Methods: SLNs were coated with chitosan (CS) followed by folic acid (FA). FA-CS-SLNs were about 284.9 nm and carried negative surface charge. Results & conclusion: FA-CS-SLNs showed sustained release profile for 168 h. Results of oral administration of FA-CS-SLNs in rats with adjuvant-induced arthritis revealed improved joint healing and reduced hepatotoxicity compared with leflunomide suspension. This may be attributed to the ability of FA-CS-SLNs to actively target FA receptors that are overexpressed in inflamed rheumatic joints in addition to innate joint healing properties of CS.


Glasgow prognostic score predicts therapeutic outcome after hepatic resection for hepatocellular carcinoma.
Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS), predicts cancer-specific survival in various cancer types. The aim of this study was to evaluate the significance of the GPS in the therapeutic outcome of the patient following surgical resection for hepatocellular carcinoma. In total, 144 patients underwent surgical resection for hepatocellular carcinoma. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10). Retrospectively, the relationship between patient characteristics including GPS, disease-free as well as overall survival were investigated. In disease-free survival, GPS 2 (P=0.019), with a tumor number ≥3 (P=0.004), and positive portal or venous invasion (P=0.034) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, GPS 1 (P=0.042), GPS 2 (P<0.001) and positive portal or venous invasion (P<0.001) were independent predictors of poor patient outcome according to multivariate analysis. To conclude, the GPS in patients with hepatocellular carcinoma is an independent prognostic predictor after hepatic resection.


Glial progenitor cells of the nerve fiber layer of the olfactory bulb: effect of astrocyte growth media.
There are two morphologically distinct types of glial cells (i.e., ensheathing cells and astrocytes) in the nerve fiber layer (NFL) of the adult mammalian olfactory bulb. Ensheathing cells provide ensheathment for olfactory axons, whereas astrocytes occupy the interfascicular spaces of the olfactory NFL. During embryonic development, however, only one type of glial cell is found in this layer of the olfactory bulb, namely, the ensheathing cell. Even though ensheathing cells take up residence within the CNS, they are actually derived from the olfactory placode. Far less is known about the developmental origin of interfascicular astrocytes, which arise either from the glial progenitor cells that give rise to ensheathing cells or from astrocyte precursor cells that migrate into the NFL from deeper layers of the bulb primordium. In the present study, enriched populations of ensheathing cells were grown in vitro in media known to promote the growth and differentiation of astrocytes to determine whether ensheathing cell progenitors could differentiate into astrocytes. These media failed to induce the appearance of astrocytes in the ensheathing cell cultures. It was concluded that the astrocytes of the NFL most likely arise from progenitor cells that migrate into this layer from deeper parts of the developing bulb.


Lessons in nonhuman primate models for AIDS vaccine research: from minefields to milestones.
Nonhuman primate (NHP) disease models for AIDS have made important contributions to the search for effective vaccines for AIDS. Viral diversity, persistence, capacity for immune evasion, and safety considerations have limited development of conventional approaches using killed or attenuated vaccines, necessitating the development of novel approaches. Here we highlight the knowledge gained and lessons learned in testing vaccine concepts in different virus/NHP host combinations.


A multicenter survey of re-treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan.
This study aimed to clarify the factors associated the efficacy of re-treatment with pegylated interferon (PEG IFN) plus ribavirin combination therapy for patients with chronic hepatitis C who had failed to respond to previous treatment. One hundred and forty-three patients who had previously shown relapse (n = 79), non-response (n = 34) or intolerance (n = 30) to PEG IFN plus ribavirin were re-treated with PEG IFN plus ribavirin. Twenty-five patients with intolerance to previous treatment completed re-treatment and the sustained virological response (SVR) rates were 55% and 80% for hepatitis C virus (HCV) genotype 1 and 2, respectively. On re-treatment of the 113 patients who completed the previous treatment, the SVR rates were 48% and 63% for genotype 1 and 2, respectively. Relapse after previous treatment and a low baseline HCV RNA level on re-treatment were associated with SVR in genotype 1 (P < 0.001). Patients with the interleukin-28B major genotype responded significantly better and earlier to re-treatment, but the difference in the SVR rate did not reach a significant level between the major and minor genotypes (P = 0.09). Extended treatment of 72 weeks raised the SVR rate among the patients who attained complete early virological response but not rapid virological response with re-treatment (72 weeks, 73%, 16/22, vs 48 weeks, 38%, 5/13, P < 0.05). Relapse after previous treatment and a low baseline HCV RNA level have predictive values for a favorable response of PEG IFN plus ribavirin re-treatment for HCV genotype 1 patients. Re-treatment for 72 weeks may lead to clinical improvement for genotype 1 patients with complete early virological response and without rapid virological response on re-treatment.


Caveolin-1 promotes Ewing sarcoma metastasis regulating MMP-9 expression through MAPK/ERK pathway.
Ewing sarcoma (ES) is a bone and soft tissue sarcoma affecting mostly children and young adults. Caveolin-1 (CAV1) is a well-known target of EWS/FLI1, the main driver of ES, with an oncogenic role in ES. We have previously described how CAV1 is able to induce metastasis in ES via matrix metalloproteinase-9 (MMP-9). In the present study we showed how CAV1 silencing in ES reduced MEK1/2 and ERK1/2 phosphorylation. Accordingly, chemical inhibition of MEK1/2 resulted in reduction in MMP-9 expression and activity that correlated with reduced migration and invasion. IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) silencing reduced MEK1/2 and ERK1/2 phosphorylation and MMP-9 expression. Furthermore, IQGAP1 silenced cells showed a marked decrease in their migratory and invasive capacity. We demonstrated that CAV1 and IQGAP1 localize in close proximity at the cellular edge, thus IQGAP1 could be the connecting node between CAV1 and MEK/ERK in ES metastatic phenotype. Analysis of the phosphorylation profile of CAV1-silenced cells showed a decrease of p-ribosomal protein S6 (RPS6). RPS6 can be phosphorylated by p90 ribosomal S6 kinases (RSK) proteins. CAV1-silenced cells showed reduced levels of p-RSK1 and treatment with U0126 provoked the same effect. Despite not affecting ERK1/2 and RPS6 phosphorylation status neither MMP-9 expression nor activity, RSK1 silencing resulted in a reduced migratory and invasive capacity in vitro and reduced incidence of metastases in vivo in a novel orthotopic model. The present work provides new insights into CAV1-driven metastatic process in ES unveiling novel key nodes.


Management of retinal detachments secondary to cytomegalovirus retinitis.
Nine patients with acquired immune deficiency syndrome underwent surgery for rhegmatogenous retinal detachments related to cytomegalovirus (CMV) retinitis. The patients were followed for at least 6 months or until death. Two patients with localized peripheral detachments for 3 to 4 clock hours or less initially underwent laser retinopexy. Although in both cases the treatment ultimately failed, one patient maintained 20/20 vision for 5 months. In four patients in whom the retinal detachment was more extensive but could be explained on the basis of a single or multiple well-defined peripheral break(s), a scleral buckle procedure was performed, with anatomic success in three, two of whom maintained 20/40 vision for 7 and 8 months. Six patients with retinal detachments associated with multiple atrophic holes that were not amenable to scleral buckling were treated with pars plana vitrectomy, air-fluid exchange and endolaser, with anatomic success in three; the visual acuity ranged from 20/30 to 20/400. One patient with failed pars plana vitrectomy underwent repeat vitrectomy with long-term internal tamponade by silicone oil, and he regained hand movements vision. We suggest a graduated approach to the management of retinal detachments secondary to CMV retinitis tailored to each patient based on the number and location of the retinal breaks, the extent of the detachment, the extent of necrotic retina and the overall health of the patient.


Microbiology, genomics, and clinical significance of the Pseudomonas fluorescens species complex, an unappreciated colonizer of humans.
Pseudomonas fluorescens is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it at low levels in the indigenous microbiota of various body sites. With recent advances in comparative genomics, many isolates originally identified as the "species" P. fluorescens are now being reclassified as novel Pseudomonas species within the P. fluorescens "species complex." Although most widely studied for its role in the soil and the rhizosphere, P. fluorescens possesses a number of functional traits that provide it with the capability to grow and thrive in mammalian hosts. While significantly less virulent than P. aeruginosa, P. fluorescens can cause bacteremia in humans, with most reported cases being attributable either to transfusion of contaminated blood products or to use of contaminated equipment associated with intravenous infusions. Although not suspected of being an etiologic agent of pulmonary disease, there are a number of reports identifying it in respiratory samples. There is also an intriguing association between P. fluorescens and human disease, in that approximately 50% of Crohn's disease patients develop serum antibodies to P. fluorescens. Altogether, these reports are beginning to highlight a far more common, intriguing, and potentially complex association between humans and P. fluorescens during health and disease.


Signal transduction pathways involved in the platelet aggregation induced by a D-49 phospholipase A2 isolated from Bothrops jararacussu snake venom.
Bothropstoxin-II (Bthtx-II), an Asp-49 phospholipase A(2) (D-PLA(2)) isolated from Bothrops jararacussu snake venom is able to induce platelet aggregation in a concentration-dependent manner. This effect was not due to the release of ADP from platelets since the aggregation was not suppressed by ADP scavenger systems. PMSF and PPACK were unable to inhibit Bthtx-II-induced platelet aggregation. Thus, a thrombin-like proaggregating activity of Bthtx-II can be excluded as its mechanism of action. On the other hand, indomethacin at low concentrations inhibited more markedly the ATP-release reaction than the aggregation induced by Bthtx-II, indicating that generation of cyclooxigenase products is not the most important event for the platelet aggregation reaction. It was also found that staurosporine and genistein suppressed both platelet aggregation and ATP-release reactions, but not the platelet shape-change induced by Bthtx-II. Substances that either directly activates adenylyl cyclase enzyme (forskolin and PGE(1)) or cell-permeant increasing agents (dibutyril-cAMP) inhibited in a concentration-dependent fashion, the platelet aggregation effects induced by the protein. It is concluded that Bthtx-II induces platelet aggregation and secretion through multiple signal transduction pathways.


Research Progress on 18F-Labeled Agents for Imaging of Myocardial Perfusion with Positron Emission Tomography.
Coronary artery disease (CAD) is the leading cause of death in the world. Myocardial perfusion imaging (MPI) plays a significant role in non-invasive diagnosis and prognosis of CAD. However, neither single-photon emission computed tomography nor positron emission tomography clinical MPI agents can absolutely satisfy the demands of clinical practice. In the past decades, tremendous developments happened in the field of 18F-labeled MPI tracers. This review summarizes the current state of 18F-labeled MPI tracers, basic research data of those tracers, and the future direction of MPI tracer research.


[The economic cost of avoidable mortality in Cartagena, Colombia, 2000-2005].
Evaluating the economic cost of loss of human capital produced by preventable deaths in Cartagena, 2000-2005, from estimating years of potential life lost (YPLL) and the percentage of years of potential productive life lost (YPPLL). This was a mixed ecological study, using 2000-2005 time series. Mortality data was taken from the Colombian National Administrative Department of Statistics (DANE) records. Cases of preventable death were classified according to Taucher's guidelines. YPLL and YPPLL were used as indicators. Deaths were adjusted by adopting WHO-recommended Bennett-Horiuchi methodology for accounting for underreporting. Two scenarios were assumed: a minimum or flat scenario and an upper or roof scenario. Once YPLL for each annual period had been established, they were multiplied by minimum income according to scenario. Epidat 3.0 software was used for analysing the database. There were 20,723 preventable deaths (adjusted for underreporting). One out of every three preventable deaths which occurred in Cartagena could have been averted by early diagnosis and medical treatment, according to Taucher. Violent deaths are the kind of avoidable deaths which produce higher costs according to the information processing (IPC) model adopted in this study. Reducing preventable deaths by early diagnosis and medical treatment would cause a significant reduction in avoidable mortality.


The biological role of protease-activated receptors in angiology. The present view.
The mechanism of initiation and growth of a thrombus in atherosclerotic arteries, although investigated extensively, has not been sufficiently elucidated. Understanding the molecular mechanisms that lead to stroke, unstable angina and myocardial infarction is of paramount importance. Protease-activated receptors (PARs) belong to a recently discovered and so far not fully characterized family of transmembrane proteins, which are involved in the initiation growth of thrombi in atherosclerotic arteries. PARs are a G-protein-coupled family of receptors which mediate a cellular function with the aid of enzymes. All of them have identical structural organization and are activated by a very similar mechanism. The enzyme (serine protease) cleaves an extracellular amino-terminal fragment of the receptor in order to unmask a new amino-terminal, 5-6 residues of which serve as the tethering ligand, able to activate its maternal receptor. According to the most recently published reports, in eukaryotic organisms there are 5 different PARs: from PAR 1 to PAR 4 found in human organisms and PAR 5 discovered as a 14-3-3 protein, identified firstly in C. elegans and Drosophila melanogaster. Up to now numerous experiments have been conducted with the aim to understand more precisely the mechanisms of PARs activation and activity. The present paper summarizes the most important and most recently published reports concerning this problem, which seems to be most relevant in angiology.


PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (<5%), moderate (10-24%), or diffuse (50-100%). The percentage of membranous carcinoma cell PD-L1 labeling was also recorded, with <5% considered negative. All lobular carcinomas contained PD-L1+ tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8+ T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1+ lobular breast carcinomas had higher numbers of PD-L1+ tumor-infiltrating lymphocytes (63%) than PD-L1- lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1+ tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.


Body fluid volume and nutritional status in hemodialysis: vector bioelectric impedance analysis.
Protein-energy malnutrition and hypervolemia are major causes of morbidity and mortality in patients on chronic hemodialysis (CHD). The methods used to evaluate nutritional status and volume status remain controversial. Vector bioelectric impedance analysis (vector- BIA) has recently been developed to assess both nutritional status and tissue hydration. The purpose of the study was to assess the nutritional status and volume status of patients on CHD with conventional nutritional assessment methods and with vector-BIA and then to compare the resulting findings. 76 Mexican patients on CHD were studied. Nutritional status and body composition were assessed with anthropometry, biochemical variables, and the modified Bilbrey nutritional index (mBNI), the results were compared with both conventional BIA and vector-BIA. The BNI was used to determine the number of patients with normal nutritional status (n = 27, 35.5%), and mild (n = 31, 40.8%), moderate (n = 10, 13.2%) and severe malnutrition (n = 8, 10.5%). Patients displayed shorter vectors with smaller phase angles or with an overhydration vectorial pattern before the initiation of their hemodialysis session. There was general improvement to normal hydration status post-dialysis (p < 0.05); however, 28% remained overhydrated as assessed by vector-BIA. The vector-BIA results showed that worse malnutrition status was associated with greater volume overload (p < 0.05). Diabetes mellitus (DM) was associated with shorter vectors with smaller phase angles (a vectorial pattern of overhydration and cachexia) (p < 0.05). Patients with lower serum creatinine presented with shorter vectors and smaller phase angles (vectorial patterns of malnutrition and/or overhydration) (p < 0.05). In women, lower serum albumin (< 3.4 g/dl) correlated with greater overhydration and malnutrition (p < 0.05). In this population, the vector-BIA showed that 28% of the population remained overhydrated after their hemodialysis session. Diabetics and those with moderate or severe malnutrition were more overhydrated, which is a condition that may be associated with increased cardiovascular morbidity. Because nutritional and volume status are important factors associated with morbidity and mortality in CHD patients, we focused on optimizing the use of existing methods. Our studies suggest that vector-BIA offers a comprehensive and reliable reproducible means of assessing both volume and masses at the bedside and can complement the traditional methods.


Deprotonative magnesation and cadmation of [1,2,3]triazolo[1,5-a]pyridines.
[1,2,3]Triazolo[1,5-a]pyridine and 3-substituted derivatives were regioselectively metalated at the 7 position using either Bu3MgLi or (TMP)3CdLi, the former at -10 degrees C and the latter at room temperature. The lithium arylmagnesates (R = H, Me, Ph) proved to react with iodine (34-75%) or 3,4,5-trimethoxybenzaldehyde (32-51%). Attempts to obtain the cross-coupling products using 2-bromopyridine under palladium catalysis failed, a result attributed to the low stability of these compounds. The corresponding lithium arylzincates reacted in 17-60% yield under the same reaction conditions. The lithium arylcadmates were either trapped with iodine (38-76%, R = H, Me, Ph, CN, 2-thienyl) or involved in palladium-catalyzed cross-coupling reactions with 2-bromopyridine (26-67%, R = H, Me, Ph). For R = 2-pyridyl, 3-(6-iodo-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridine was isolated in 73% yield. (TMP)3CdLi also proved suitable for the clean dideprotonation of two substrates (R = H, 2-thienyl), a result demonstrated by quenching with iodine (66-75%).


A descriptive exploration of the geographic and sociodemographic concentration of firearm homicide in the United States, 2004-2018.
This study examined the population-based incidence of firearm homicide in the United States to identify geographic concentrations and to determine whether such concentrations have changed over time. It further examined the simultaneous associations of urbanization, poverty, and ethnicity/race with firearm homicide incidence. Using county-level data from the National Vital Statistics System and the U.S. Census Bureau for the years 2004-2018, the findings show geographic patterns not commonly recognized, including several lengthy and continuous corridors with a high incidence of firearm homicide, traversing both metro and non-metro areas. While the data clearly show a strongly disproportionate concentration of firearm homicide incidence in a subset of the population defined by geography, they do not suggest increasing concentration over time. The study findings also generally indicate increasing firearm homicide incidence with increasing levels of surrounding poverty, a phenomenon observed for both metro and non-metro areas.


Chemical methylation of RNA and DNA viral genomes as a probe of in situ structure.
We used [methyl-(3)H] dimethyl sulfate to probe the genome structures of several RNA and DNA viruses. We compared sites of modification in nucleic acids that were methylated chemically before and after extraction from purified virions. With both single-stranded and double-stranded substrates alkylation occurred mainly at the N7 position of guanine. However, adenine N1 atoms were differentially accessible in single-stranded RNA and DNA. For example, the ratios of 1-methyladenosine to 7-methylguanosine for reovirus mRNA and deproteinized genome RNA were 0.43 and 0.03, respectively. Members of the Reoviridae methylated in situ yielded RNAs with ratios of 0.04 to 0.08, indicating that the intravirion genomes were double stranded. We obtained ratios of 0.26 and 0.35 for the RNAs of dimethyl sulfate-treated brome mosaic and avian sarcoma virions, respectively, which was consistent with partial protection of adenine N1 sites by structural proteins or genome conformation or both. The ratios of 1-methyladenosine to 7-methylguanosine for vaccinia virus DNAs methylated in situ (0.10) and after phenol extraction (0.14) were less than the ratios for phiX174 and M13 DNAs (0.39 to 0.64) but considerably greater than the ratio observed with adenovirus DNA (0.002 to 0.02). The presence of a single-stranded region(s) in the vaccinia virus genome was confirmed by S1 nuclease digestion of [methyl-(3)H] DNA; the released radiolabeled fraction had a ratio of 0.41, compared with 0.025 for the residual duplex DNA. In addition to the structure-dependent accessibility of adenine N1, methylation of adenine N3 was severalfold lower in the intravirion genomes of vaccinia virus, phiX174, and adenovirus than in the corresponding extracted DNAs. Chemical methylation of virions and subviral particles should be useful for in situ analyses of specific regions of RNA and DNA genomes, such as the sites of protein binding during virus maturation.


[Total hip arthroplasty in patients with cerebral vascular event. Case report].
Associated neurological disorders pose a challenge hip joint reconstruction. The imbalance and poor muscle tone predispose to dislocation and loosening of the prosthesis. The following is the case of a 67 years old patient with a hemorrhagic cerebral vascular event with a secondary left hemiparesis. Ten years later had a femoral neck fracture on the affected side. Initially she was treated with conservative management resulting in pain and discapacity, valued with WOMAC scale as 12 points. Two years later was treated with total hip arthroplasty with large diameter femoral head. We present the follow up of 41 months, asymptomatic, walking using a cane and a WOMAC score of 41, with no signs of radiological loosening or dislocation. There is no experience documented in neurological disorders associated with hip diseases that requires a total hip arthroplasty. Loosening of the implants, dislocation and heterotopic ossification has been described as complications of the procedure. Large heads in total hip arthroplasty and a correct surgical technique associated with a multidisciplinary management in patients with neurological disorders offers an opportunity as a treatment in patient with hip disorders.


Effects of fenofibrate and xuezhikang on high-fat diet-induced non-alcoholic fatty liver disease.
1. Fenofibrate and xuezhikang are two types of drugs widely used in the treatment of dyslipidaemia in China. The main purpose of present study was to test the efficacies and explore the potential mechanisms of action of the two lipid-lowering agents on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD). 2. Rats were randomly divided into four groups, with eight rats per group. One group was given normal diet, whereas the other three groups were fed a high-fat diet. Forty-two days later, two of the high-fat diet-fed groups were administered fenofibrate (100 mg/kg, p.o.) and xuezhikang (300 mg/kg, p.o.) for another 42 consecutive days. The other two groups were administered placebo (saline) by gavage. 3. Typical pathological symptoms of NAFLD occurred in the high-fat diet groups. Fenofibrate and xuezhikang treatment markedly improved NAFLD, ameliorating dyslipidaemia and fat accumulation in the liver, improving insulin resistance and ameliorating oxidative stress. Hepatic steatosis, necro-inflammation and collagen deposition were lessened in the drug-treated groups. However, both xuezhikang and fenofibrate failed to reverse hepatomegaly and fenofibrate even aggravated it. Xuezhikang reversed aminotransferase abnormalities, but fenofibrate had less of an effect. 4. The common therapeutic mechanism of action of fenofibate and xuezhikang likely involves inhibition of the hepatic expression of tumour necrosis factor-alpha. Fenofibrate upregulated mRNA levels of peroxisome proliferator-activated receptor (PPAR) alpha in the liver, whereas xuezhikang had no effect on the hepatic expression of PPARalpha and this may explain, in part, their different effects on the NAFLD rats. 5. The results suggest that fenofibrate and xuezhikang may have potential clinical application in the treatment of NAFLD. However, the side-effects of fenofibrate and the underlying constituents of xuezhikang need to be determined and investigated further.


Early Increase in Cortical T2 Relaxation Is a Prognostic Biomarker for the Evolution of Severe Cortical Damage, but Not for Epileptogenesis, after Experimental Traumatic Brain Injury.
Prognostic biomarkers for post-injury outcome are necessary for the development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI). We hypothesized that T2 relaxation magnetic resonance imaging (MRI) predicts the progression of perilesional cortical pathology and epileptogenesis. The EPITARGET animal cohort used for MRI analysis included 120 adult male Sprague-Dawley rats with TBI induced by lateral fluid-percussion injury and 24 sham-operated controls. T2 MRI was performed at days 2, 7, and 21 post-TBI. The lesioned cortex was outlined, and the T2 value of each imaging voxel within the lesion area was scored using a five-grade pathology classification. Analysis of 1-month video-electroencephalography recordings initiated 5 months post-TBI indicated that 27% (31 of 114) of the animals with TBI developed epilepsy. Multiple linear regression analysis indicated that T2-based classification of lesion volume at day 2 and day 7 post-TBI explained the necrotic lesion volume with greatly increased T2 (>102 ms) at day 21 post-TBI (F(13,103) = 52.5; p < 0.001; R2 = 0.87; adjusted R2 = 0.85). The volume of moderately increased (78-102 ms) T2 at day 7 post-TBI predicted the evolution of large (>12 mm3) cortical lesions (area under the curve, 0.92; p < 0.001; cutoff, 1.9 mm3; false positive rate, 0.10; true positive rate, 0.62). Logistic regression analysis, however, showed that the different severities of T2 lesion volumes at days 2, 7, and 21 post-TBI did not explain the development of epilepsy (χ2(18,95) = 18.4; p = 0.427). In addition, the location of the T2 abnormality within the cortex did not correlate with epileptogenesis. A single measurement of T2 relaxation MRI in the acute post-TBI phase is useful for identifying post-TBI subjects at highest risk of developing large cortical lesions, and thus, in the greatest need of neuroprotective therapies after TBI, but not the development of post-traumatic epilepsy.


Successful management of a large pulmonary cement embolus after percutaneous vertebroplasty: a case report.
Percutaneous vertebroplasty is increasingly used for the treatment of vertebral compression fractures. Local leakage of polymethylmethacrylate cement into the perivertebral space is a common complication, but important systemic effects have rarely been reported. The authors describe the case of a 52-year-old patient with central pulmonary embolism after percutaneous vertebroplasty of the eleventh thoracic vertebral body. The large cement embolus was removed from the right pulmonary artery with a hybrid technique combining an interventional catheter procedure with an open heart operation. The patient made an uneventful recovery. The authors review how appropriate arthroplasty techniques might minimize the risk of this dreadful complication.