Characterization of a novel antioxidant peptide from feather keratin hydrolysates.
Feather hydrolysates were obtained through submerged cultivation of 50 g/L feathers with Chryseobacterium sp. kr6. Culture supernatants, displaying antioxidant properties, as evaluated by the 2,2'-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical scavenging method, were partially purified by gel-filtration chromatography. Fractions showing scavenging activity were pooled, lyophilized and tested at different concentrations (0.1-1.0 mg/mL) by the total reactive antioxidant potential (TRAP) method, showing promising antioxidant capacities. Antioxidant activities of the partially purified feather hydrolysate (PPFH; 24.5 μg) were demonstrated by its ability to scavenge hydroxyl radicals and to inhibit lipid peroxidation. In addition, PPFH (0.24-24.5 μg) was found to reduce ferric ion (Fe3+), but did not display Fe2+-chelating activity. Thus, the main antioxidant activities could be related to the donation of hydrogen atoms, electron transfer and scavenging of hydroxyl radicals. PPFH was analyzed by mass spectrometry and five peptides were identified and chemically synthesized. The antioxidant activity of one peptide LPGPILSSFPQ was confirmed by ABTS and TRAP. The structure of this keratin-derived bioactive peptide has not been previously described.


Efficacy of a decision support intervention for reducing decisional conflict in patients with elevated serum prostate-specific antigen: A randomized controlled trial.
The study purpose is to test the efficacy of a decision support intervention for reducing decisional conflict, increasing prostate biopsy knowledge, and enhancing decision self-efficacy in patients with elevated serum prostate-specific antigen. The study is based on a randomized pre-post test design. A convenience sample of men with elevated prostate-specific antigen was recruited and 1:1 randomized to the intervention and control groups. The intervention group received the decision support intervention and the control group received health education. Data were collected at the baseline and post-test by using self-reported questionnaires, including the Prostate Biopsy Knowledge Scale, the Decision Self-Efficacy Scale, the Decisional Conflict Scale, and questions regarding the prostate biopsy decision (post-test only). Data on prostate-specific antigen levels were collected from the patients' medical records. A total of 110 patients participated in the study. At baseline, the intervention group had significantly higher knowledge scores than the control group. The analysis of the covariance model with the baseline score as a covariate was used to analyze the intervention effect. After controlling for the baseline scores, the mean differences (95% CI) between the two groups were 11.75 (11.17-12.32), 76.45 (72.52-80.37), and -23.53 (-26.31-20.20) for knowledge, decision self-efficacy, and decisional conflict, respectively. The between-group difference in willingness to accept prostate biopsy at the post-test was not statistically significant (χ2= 1.704). The decision support intervention significantly reduced patients' decisional conflict while improving their knowledge and self-efficacy. However, the intervention did not affect patients' biopsy decision.


"I don't need people to tell me I'm pretty on social media:" A qualitative study of social media and body image in early adolescent girls.
Social media appear to contribute to body dissatisfaction in adolescents, although few empirical studies exist. This study used six focus groups (total N=38) to explore relations between social media use and body image in early adolescent girls (ages 12-14). Thematic analysis identified patterns in the data. In this sample, social media use was high. Girls endorsed some appearance concerns and social comparison, particularly with peers. However, they displayed high media literacy, appreciation of differences, and confidence, strategies that appeared helpful in mitigating the potential negative association between social media exposure and body image. Girls reported these characteristics were nurtured by positive parental influence and a supportive school environment. Results support an ecological approach to the prevention of body dissatisfaction. Although peer influence strengthens throughout adolescence, current findings suggest that parents and the school environment are associated with girls' attitudes and behaviors regarding social media and body image.


When pigs fly: emotional support animals, service dogs and the politics of legitimacy across species boundaries.
This paper probes the distinction between the so-called emotional support animals (ESAs), a term that is specific to the USA and that has recently been the subject of significant media attention, and service animals. The attention devoted to ESAs has largely taken on the form of jokes and critical comments related to the absurdity of the 'political correctness' that makes it possible for pigs to fly in the passenger cabin of airplanes and llamas to accompany their owners on trips to the supermarket. Much criticism is meted out, also from within the disability community, against animal guardians who try to 'pass their animals off' as service dogs and ESAs, with a call for the establishment of clear-cut criteria for the definition of ESAs and service animals. The paper's methodology is an analysis of the media accounts of legitimate and illegitimate service animals; an analysis that reveals how the boundary between legitimate and illegitimate is constructed through the building blocks of these stories. ESAs are something of a limit case that points to the cultural paradoxes that govern Americans' relationships with companion animals and with concepts of disability. The paper also argues that the insistence on establishing firm boundaries between 'legitimate' service animals and ESAs actually fosters a politics of suspicion, which can easily slip into suspicion directed at the human handlers of the animals.


Feedback regulation of pancreatic secretion by peptide YY.
The present status of our understanding of the feedback regulation of pancreatic secretion by peptide YY (PYY) released from the distal intestine is reviewed. Exocrine pancreatic secretion is primarily controlled by the cephalic (the vagus nerve), gastric (acid and pepsin secretion, and nutrients delivered into the duodenum by gastric emptying), and intestinal (secretin and CCK) mechanisms. PYY acts on the multiple sites in the brain and gut, and inhibits pancreatic secretion by regulating these primary control mechanisms. The involvement of Y(1) and Y(2) receptors has been suggested in the regulation of pancreatic secretion. However, it remains to be studied which site of action or receptor subtype is physiologically most important for this regulation.


Utility of a rapid assay for prostaglandin E-major urinary metabolite as a biomarker in pediatric ulcerative colitis.
Prostaglandin E-major urinary metabolite (PGE-MUM) is a urinary biomarker reflecting ulcerative colitis (UC) activity. This prospective observational study aimed to evaluate the usefulness of PGE-MUM via rapid chemiluminescent enzyme immunoassay in detecting endoscopic remission (ER) and histologic remission (HR) in pediatric UC (6-16 years) in comparison with fecal calprotectin (FCP). ER and HR were defined as Mayo endoscopic score (MES) of 0 and Matts' histological grades (Matts) of 1 or 2, respectively. A total of 104 UC and 39 functional gastrointestinal disorder (FGID) were analyzed. PGE-MUM levels were significantly higher in the UC group than in the FGID group (P < 0.001). FCP levels were significantly elevated in the group without ER and HR than in the group with ER and HR (P < 0.001 and P = 0.001), whereas PGE-MUM levels were significantly higher in the group without ER compared to the group with ER (P < 0.001). No significant differences were noted in the AUCs for PGE-MUM and FCP in detecting ER and HR. Although PGE-MUM was inferior to FCP for the detection of HR, it might have the potential for application as a biomarker of endoscopic activity in pediatric UC owing to its noninvasive and rapid method.


Selective introduction of TMS groups in tryptamines: preparation of N1-TMS derivatives of tryptamines.
Indolethylamines (tryptamines) with a primary animofunction react with Regisil under controlled conditions to yield a mono TMS derivative. Mass spectrometry to these derivatives shows that the TMS group is substituted on the indolic nitrogen (N1) and not the primary amino nitrogen. This is confirmed by converting these compounds to their isothiocyanate derivatives. The GC and GC-MS data of some typical compounds are presented.


Selective Targeted Drug Delivery Mechanism via Molecular Imprinted Polymers in Cancer Therapeutics.
Artificial receptor-like structures such as molecular imprinted polymers (MIPs) are biomimetic molecules are used to replicate target specific antibody-antigen mechanism. In MIPs, selective binding of template molecule can be significantly correlated with lock and key mechanism, which play a major role in the drug delivery mechanism. The MIPs are biocompatible with high efficiency and are considered in several drug delivery and biosensor applications besides continuous and controlled drug release leading to better therapeutics. There is a need to explore the potential synthetic methods to improve MIPs with respect to the imprinting capacity in cancer therapeutics. In this review, we focus on MIPs as drug delivery mechanism in cancer and the challenges related to their synthesis and applications.


Maternal immune response in the placenta of sheep during recrudescence of natural congenital infection of Neospora caninum.
In order to gain further insight into the pathogenesis and transmission of ovine neosporosis, the serological response of 13 naturally infected pregnant sheep was monitored. All sheep were euthanized upon the detection of a sharp increase in the level of specific antibodies against N. caninum in order to study the maternal immune response after the recrudescence of a chronic infection. Ten sheep were euthanized between 84 and 118 days of gestation, whereas the three remaining and three control not infected, pregnant sheep were euthanized at 135 days of gestation after no sharp increase in antibodies was detected. Vertical transmission was confirmed in 11 sheep by detection of N. caninum-DNA in at least one fetus, confirming recrudescence. Not all of fetuses showed pathologic microscopic lesions, however, multifocal non-purulent encephalitis was the main finding. Furthermore, nine out of the 11 vertical transmission positive sheep had lesions in placentomes (mainly multifocal necrotic foci), and the parasite was detected in eight out of 11 placentas by PCR and/or immunohistochemestry. The placentomes from sheep that suffered recrudescence showed an increased number of T lymphocytes CD3+ (CD4/CD8 < 1) and macrophages (MHC-II+), assessed by immunohistochemestry, together with an up-regulation of IFN-γ, IL-10, IL-4, TNFα, IL-2 and IL-18. IL-17 was only upregulated in the three infected sheep that did not have a sharp increase in antibody levels. In the sheep that showed fetal death at the time of euthanasia (n = 3) the placental microscopic lesions were more severe, the inflammatory infiltrate was higher, and the upregulation of cytokines was greater than in those sheep carrying viable fetuses. This study suggests that, similarly to bovine neosporosis, the time of gestation when recrudescence occurs determines the viability of the fetuses and, thus, seems to be related to the severity of lesions and immune response in the placenta. These results suggest that there might be a correlation, either as cause or as a consequence, between protection against vertical transmission of the parasite and a milder maternal serological response together with a high level of transcription of IL-17 in the placenta.


Nutrition and skin. Collagen integrity: a dominant role for amino acids.
The skin is an important organ, and the need for attention to its metabolic requirements is often underestimated by professionals involved with its integrity and beauty. Amino acids are the indispensable nutritional basis for the maintenance of its integrity. The skin has very peculiar amino acid needs, which should be acknowledged and supplied if necessary.


The detection of porphyria in photosensitive patients.
The biochemical diversity of the various porphyris often leads to incomplete investigation of photosensitive patients and porphyria may be excluded wrongly on the basis of normal urinary porphyrins alone. Establishing a biochemical referral centre for photosensitive patients suspected of having porphyria led to the diagnosis of 5 cases of porphyria cutanea tarda (PCT) and 2 cases of erythropoietic protoporphyria (EPP) among 34 patients referred by dermatologists over a period of 12 months. Iron overload was conformed in 3 the PCT patients by plasma ferritin assay. Studies on the available families of the two EPP patients revealed elevated red cell protoporphyrin levels in several clinically asymptomatic relatives.


Modulation of aggregation and structural polymorphisms of β-amyloid fibrils in cellular environments by pyroglutamate-3 variant cross-seeding.
Amyloidogenic deposition of β-amyloid (Aβ) peptides in human brain involves not only the wild-type Aβ (wt-Aβ) sequences, but also posttranslationally modified Aβ (PTM-Aβ) variants. Recent studies hypothesizes that the PTM-Aβ variants may trigger the deposition of wt-Aβ, which underlies the pathology of Sporadic Alzheimer's disease. Among PTM-Aβ variants, the pyroglutamate-3-Aβ (pyroE3-Aβ) has attracted much attention because of their significant abundances and broad distributions in senile plaques and dispersible and soluble oligomers. pyroE3-specific antibodies are being tested as potential anti-Aβ drugs in clinical trials. However, evidence that support the triggering effect of pyroE3-Aβ on wt-Aβ in cells remain lacking, which diminishes its pathological relevance. We show here that cross-seeding with pyroE3-Aβ40 leads to accelerated extracellular and intracellular aggregation of wt-Aβ40 in different neuronal cells. Cytotoxicity levels are elevated through the cross-seeded aggregation, comparing with the self-seeded aggregation of wt-Aβ40 or the static presence of pyroE3-Aβ40 seeds. For the extracellular deposition in mouse neuroblastoma Neuro2a (N2a) cells, the cytotoxicity elevation correlates positively with the seeding efficiency. Besides aggregation rates, cross-seeding with pyroE3-Aβ40 also modulates the molecular level structural polymorphisms of the resultant wt-Aβ40 fibrils. Using solid-state nuclear magnetic resonance (ssNMR) spectroscopy, we identified key structural differences between the parent pyroE3/ΔE3 and wt-Aβ40 fibrils within their fibrillar cores. Structural propagation from seeds to daughter fibrils is demonstrated to be more pronounced in the extracellular seeding in N2a cells by comparing the ssNMR spectra from different seeded wt-Aβ40 fibrils, but less significant in the intracellular seeding process in human neuroblastoma SH-SY5Y cells.


The Value of Chinese Thyroid Imaging Report and Data System Combined With Contrast-Enhanced Ultrasound Scoring in Differential Diagnosis of Benign and Malignant Thyroid Nodules.
To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P < .001), respectively. The CEUS feature of mild enhancement in the arterial phase and rapid wash-out pattern are suggestive of malignancy and isochronous wash-out pattern is suggestive of benignity. The C-TIRADS + CEUS score has a higher value for distinguishing benign from malignant thyroid nodules than the C-TIRADS score alone.


Dapagliflozin as an adjunct therapy to insulin in the treatment of patients with type 1 diabetes mellitus.
We have evaluated the efficacy of dapagliflozin in patients with type 1 diabetes mellitus (DM1) without adequate control. We expected that adding dapagliflozin to this population on top of their base treatment would lower their HbA1c levels. We conducted a pragmatic, open, 24-week study of treatment with 10 mg of oral dapagliflozin in patients with DM1 and chronic hyperglycemia. We evaluated glycemic control, lipid profile, weight, and insulin dose. Safety was assessed by adverse event reporting. Fasting glucose levels decreased from 176.42 ± 45.33 mg/dL to 139.67 ± 44.42 mg/dL (p = 0.05); although no significant valued was reached, postprandial glucose showed a decreased tendency from 230.25 ± 52.06 mg/dL to 193.83 ± 45.43 mg/dL (p = 0.08). The hemoglobin A1C (HbA1C) level decreased from 9.18 ± 1.02 (77 ± 11.1 mmol/mol) to 8.05 ± 1.09 % (64 ± 11.9 mmol/mol) (p = 0.0156); total cholesterol decreased from 299 ± 12 to 199 ± 7 mg/dL (p = 0.02); triglycerides decreased from 184 ± 15 to 160 ± 11 mg/dL (p = 0.0002), HDL-C decreased from 40 ± 17 to 42 ± 9 mg/dL (p = 0.54); and LDL-C decreased from 187 ± 19 to 170 ± 21 mg/dL (p = 0.049). No adverse events were reported. The beneficial effects of SGLT2 inhibitors on metabolic control and their safety after a 24-week open study demonstrate their potential indication as an adjunctive treatment with insulin in patients with DM1; however, long-term clinical trials should be considered.


Reactions of 7- and 9-aminoadenines with 2,4-pentanedione. Formation of new ring systems, pyridazino[6,1-f]purine and pyridazino[1,6-e]purine.
Reactions of 7-aminoadenines with 2,4-pentanedione yielded pyridazino[6,1-f]purines and 5-pyrazolylpyrimidines. The structure of the latter was identified by X-ray analysis. Reaction of 9-amino-N6-methyladenine with 2,4-pentanedione gave pyridazino[1,6-e]purine and Schiff base products. Possible reaction mechanisms are discussed.


Hyphenated techniques for the analysis of heparin and heparan sulfate.
The elucidation of the structure of glycosaminoglycan has proven to be challenging for analytical chemists. Molecules of glycosaminoglycan have a high negative charge and are polydisperse and microheterogeneous, thus requiring the application of multiple analytical techniques and methods. Heparin and heparan sulfate are the most structurally complex of the glycosaminoglycans and are widely distributed in nature. They play critical roles in physiological and pathophysiological processes through their interaction with heparin-binding proteins. Moreover, heparin and low-molecular weight heparin are currently used as pharmaceutical drugs to control blood coagulation. In 2008, the health crisis resulting from the contamination of pharmaceutical heparin led to considerable attention regarding their analysis and structural characterization. Modern analytical techniques, including high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, and nuclear magnetic resonance spectroscopy, played critical roles in this effort. A successful combination of separation and spectral techniques will clearly provide a critical advantage in the future analysis of heparin and heparan sulfate. This review focuses on recent efforts to develop hyphenated techniques for the analysis of heparin and heparan sulfate.


Experiences with the measurement of inhibitory activity of urine and crystallisation inhibitors by different techniques.
The effect of urine, pyrophosphate (PPi), citrate and diphosphonate on the formation, the growth rate or the aggregation of calcium oxalate or calcium phosphate crystals was measured by 4 different methods. The degree of supersaturation and the area of crystal surface present in the test systems were found to be limiting factors for the action of inhibitors. Citrate and PPi proved to be important urinary inhibitors of the growth of calcium oxalate crystals. Comparison between stone formers and healthy controls revealed a significant lack of PPi in urine of male patients. The inhibitory effect of PPi in urine of healthy people was enhanced by unknown factors. This enhancement could not be found in about 60% of the stone patients. Problems relating to measurement and clinical importance of inhibitors are discussed.


The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.
Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.


Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product.
The adenovirus E1A gene product, the simian virus 40 large tumor antigen, and the human papillomavirus E7 protein share a short amino acid sequence that constitutes a domain required for the transforming activity of these proteins. These sequences are also required for these proteins to bind to the retinoblastoma gene product (pRb). Recent experiments have shown that E1A can dissociate complexes containing the transcription factor E2F bound to pRb, dependent on this conserved sequence element. We now show that the E7 protein and the simian virus 40 large tumor antigen can dissociate the E2F-pRb complex, dependent on this conserved sequence element. We also find that the E2F-pRb complex is absent in various human cervical carcinoma cell lines that either express the E7 protein or harbor an RB1 mutation, suggesting that the loss of the E2F-pRb interaction may be an important aspect in human cervical carcinogenesis. We suggest that the ability of E1A, the simian virus 40 large tumor antigen, and E7 to dissociate the E2F-pRb complex may be a common activity of these viral proteins that has evolved to stimulate quiescent cells into a proliferating state so that viral replication can proceed efficiently. In circumstances in which a lytic infection does not proceed, the consequence of this action may be to initiate the oncogenic process in a manner analogous to the mutation of the RB1 gene.


[Retrospective study of 56 congenital diaphragmatic hernias. Prognostic factors, therapeutic deductions].
Fifty-six neonates were treated for congenital diaphragmatic hernia (48 left and 8 right) in our intensive care unit from 1972 to 1980. Because of the high mortality, we studied the factors which could predict the outcome. Early onset of symptoms (before the 2nd hour of life) and low post-ductal shunt (PAO2/FiO2 less then 15) after the 3rd postoperative hour appear to be signs of poor prognosis. Our present attitude is early surgical procedure, controlled ventilation with a FiO2 1 with Pancuronium, prevention of pneumothorax and different use of pulmonary arterial vasodilatators.


Analysis of transcriptional profiles and functional clustering of global cerebellar gene expression in PCD3J mice.
The Purkinje cell degeneration (PCD) mutant mouse is characterized by a degeneration of cerebellar Purkinje cells and progressive ataxia. To identify the molecular mechanisms that lead to the death of Purkinje neurons in PCD mice, we used Affymetrix microarray technology to compare cerebellar gene expression profiles in pcd3J mutant mice 14 days of age (prior to Purkinje cell loss) to unaffected littermates. Microarray analysis, Ingenuity Pathway Analysis (IPA) and expression analysis systematic explorer (EASE) software were used to identify biological and molecular pathways implicated in the progression of Purkinje cell degeneration. IPA analysis indicated that mutant pcd3J mice showed dysregulation of specific processes that may lead to Purkinje cell death, including several molecules known to control neuronal apoptosis such as Bad, CDK5 and PTEN. These findings demonstrate the usefulness of these powerful microarray analysis tools and have important implications for understanding the mechanisms of selective neuronal death and for developing therapeutic strategies to treat neurodegenerative disorders.


'A different kind of space': Mixed methods evaluation of facilitated reflective practice groups for nurses in an acute inpatient mental health unit.
Despite recognising the value of reflective practice, there are challenges in implementation of clinical supervision for nurses. This study reports on the implementation of Reflective Practice Groups for nurses in an acute inpatient mental health setting as a means of introducing nurses to reflective practice. A mixed-methods approach explored participant and facilitator experiences through session evaluation questionnaires, facilitator field notes, and interviews with participants. Findings demonstrate challenges in implementing Reflective Practice Groups however the perceived benefits suggest promise in using Reflective Practice Groups to engage busy nurses in facilitated reflection with an aim to transition to reflective clinical supervision.


The assembly of Ni2+-actin: some peculiarities.
Nickel alters the organisation of highly dynamic cytoskeletal elements. In cultured cells Ni2+ causes microtubule aggregation and bundling as well as microfilament aggregation and redistribution. Here, we have analysed the effect(s) of Ni2+ on in vitro actin polymerisation. Using limited proteolysis by trypsin we have suggested that the regions around Arg-62 and Lys-68 change their conformation following Ni2+ binding to the single high-affinity site for divalent cations in the G-actin molecule. We have found that Ni2+ shortens the lag phase of actin polymerisation and increases the rate of assembly mainly because of an increased elongation rate. Ni2+ has no significant effect on the final plateau of actin polymerisation nor on the actin critical concentration. Electron microscopy revealed that actin filaments polymerised by 2 mM Ni2+ showed some tendency to lateral aggregation, being frequently formed by the cohesion of two or three filaments. Furthermore, they often appeared shorter than those of control as also confirmed by the larger amount of free filament ends as well as the faster depolymerisation rate than control.


Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?
Malignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy. All LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included. The study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1-68) and was 63.0 (18-79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)-based to an everolimus-based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5-year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non-PTLD N+ stage malignancy (HR = 5.52 95%CI [1.40;21.69], p = .014), non-PTLD M+ stage malignancy (HR = 10.55 95%CI [3.20;34.73], p = .0001), and suboptimal chemotherapy (HR = 2.73 95%CI [1.34;5.56], p = .005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy. The present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts.


Mitotic spindle fiber orientation in relation to cell migration in the neo-cortex of normal and reeler mouse.
The angular distribution of mitotic spindle fibers has been studied in the telencephalic ventricular zone (VZ) of mouse embryos and has been found to be monophasic and invariant during the early cortical histogenesis both in the normal and in a reeler embryo. This observation suggests that the orientation of mitotic spindle fibers is independent of nerve cell migration in the embryonic cortex.


Flexor digitorum accessorius causing tarsal tunnel syndrome in a paediatric patient: A case report and review of the literature.
The flexor digitorium accessorius muscle is an unusual anatomical variant found in the posteromedial aspect of the hindfoot and ankle. As previously described, its location predisposes patients to developing tarsal tunnel syndrome. This case illustrates the diagnosis, treatment and resolution of tarsal tunnel syndrome in a paediatric patient, secondary to the presence of flexor digitorium accessorius muscle.


Suppression of pilocarpine-induced ictal oscillations in the hippocampal slice.
Activation of muscarinic cholinergic receptors produces oscillations in the hippocampal slice that resemble the theta rhythm, but also may produce abnormal synchronous activity that is more characteristic of epileptiform activity. We used pilocarpine, a muscarinic agonist and convulsant, and an elevation in extracellular potassium (5-7.5 mM) to produce synchronous neuronal activity that was prolonged (>2 s) and mimicked synchronization noted during seizures in vivo (ictal activity). In the CA3 region of adult rat hippocampal slices, prolonged ictal oscillations consisted of rhythmic field potentials occurring at 4-10 Hz for up to 30 s (ictal duration) that occurred in a regular periodic pattern every 12-166 s (ictal interval). The duration and interval between ictal oscillations were measured before and after application of drugs to define determinants of ictal occurrence. High threshold calcium channel antagonists (nifedipine and verapamil) blocked ictal activity. Release of calcium from intracellular stores also appeared to be important for ictal synchronization because ictal activity was blocked by dantrolene, an inhibitor of calcium release from intracellular stores, and by thapsigargin which blocks the ATPase that maintains intracellular calcium stores. These suppressive effects appeared to be postsynaptic because nifedipine, dantrolene, and thapsigargin had no effect on evoked fEPSPs. Enhancement of presynaptic inhibition by activation of GABA(B) or adenosine A(1) receptors suppressed ictal activity and depressed the amplitude of evoked population synaptic potentials. The results point to an important role for high threshold calcium channels and release of calcium from intracellular stores in addition to strength of synaptic connections in generation of prolonged oscillations that underlie seizure activity.


A large-scale systematic survey reveals recurring molecular features of public antibody responses to SARS-CoV-2.
Global research to combat the COVID-19 pandemic has led to the isolation and characterization of thousands of human antibodies to the SARS-CoV-2 spike protein, providing an unprecedented opportunity to study the antibody response to a single antigen. Using the information derived from 88 research publications and 13 patents, we assembled a dataset of ∼8,000 human antibodies to the SARS-CoV-2 spike protein from >200 donors. By analyzing immunoglobulin V and D gene usages, complementarity-determining region H3 sequences, and somatic hypermutations, we demonstrated that the common (public) responses to different domains of the spike protein were quite different. We further used these sequences to train a deep-learning model to accurately distinguish between the human antibodies to SARS-CoV-2 spike protein and those to influenza hemagglutinin protein. Overall, this study provides an informative resource for antibody research and enhances our molecular understanding of public antibody responses.


Loss of maternally derived human herpesvirus-6 immunity and natural infection in Argentinian infants.
Human herpesvirus-6 (HHV-6) infection is widespread throughout the world. No data are available in Argentina about the loss of maternally derived HHV-6 immunity and natural infection in infants. A population of 100 pregnant women and 407 children between 1 and 15 months of age were assayed by indirect immunofluorescence to detect and quantify specific IgG anti-human herpesvirus-6 (anti-HHV-6) antibodies in Córdoba City, Argentina. There was no significant difference in the positive rate between infants aged 1 to 9 months (range, 43.6 35.5%) and pregnant women (37%). Seropositive ratio dropped in the 10-month group (23.33% seropositive) and rose sharply in the 11-month group (38.89%), 12-month (60.61%), and 13- to 15-month group (63.46%). The geometric mean titer (GMT) for infants in the 12 to 15 months age group (23.4 41.64) was significantly higher than the GMT for infants 10 months of age (11.04) (P < 0.05 with the Tukey-HSD test). This study shows a significant association between loss of passive HHV-6 antibody and age among infants. The results support evidence that HHV-6 enters the susceptible population at 11 months, leading to a high prevalence of antibodies in children between 13 and 15 months of age.


Cell cycle phase classification in 3D in vivo microscopy of Drosophila embryogenesis.
Cell divisions play critical roles in disease and development. The analysis of cell division phenotypes in high content image-based screening and time-lapse microscopy relies on automated nuclear segmentation and classification of cell cycle phases. Automated identification of the cell cycle phase helps biologists quantify the effect of genetic perturbations and drug treatments. Most existing studies have dealt with 2D images of cultured cells. Few, if any, studies have addressed the problem of cell cycle classification in 3D image stacks of intact tissues. We developed a workflow for the automated cell cycle phase classification in 3D time-series image datasets of live Drosophila embryos expressing the chromatin marker histone-GFP. Upon image acquisition by laser scanning confocal microscopy and 3D nuclear segmentation, we extracted 3D intensity, shape and texture features from interphase nuclei and mitotic chromosomes. We trained different classifiers, including support vector machines (SVM) and neural networks, to distinguish between 5 cell cycles phases (Interphase and 4 mitotic phases) and achieved over 90% accuracy. As the different phases occur at different frequencies (58% of samples correspond to interphase), we devised a strategy to improve the identification of classes with low representation. To investigate which features are required for accurate classification, we performed feature reduction and selection. We were able to reduce the feature set from 42 to 9 without affecting classifier performance. We observed a dramatic decrease of classification performance when the training and testing samples were derived from two different developmental stages, the nuclear divisions of the syncytial blastoderm and the cell divisions during gastrulation. Combining samples from both developmental stages produced a more robust and accurate classifier. Our study demonstrates that automated cell cycle phase classification, besides 2D images of cultured cells, can also be applied to 3D images of live tissues. We could reduce the initial 3D feature set from 42 to 9 without compromising performance. Robust classifiers of intact animals need to be trained with samples from different developmental stages and cell types. Cell cycle classification in live animals can be used for automated phenotyping and to improve the performance of automated cell tracking.


Detection of pediatric obstructive sleep apnea syndrome: history or anatomical findings?
To assess how history and/or anatomical findings differ in diagnosing pediatric obstructive sleep apnea (OSA). Children aged 2-18 years were recruited and assessed for anatomical (ie, tonsil size, adenoid size, and obesity) and historical findings (ie, symptoms) using a standard sheet. History and anatomical findings, as well as those measures significantly correlated with OSA, were identified to establish the historical, anatomical, and the combined model. OSA was diagnosed by polysomnography. The effectiveness of those models in detecting OSA was analyzed by model fit, discrimination (C-index), calibration (Hosmer-Lemeshow test), and reclassification properties. A total of 222 children were enrolled. The anatomical model included tonsil hypertrophy, adenoid hypertrophy, and obesity, whereas the historical model included snoring frequency, snoring duration, awakening, and breathing pause. The C-index was 0.84 for the combined model, which significantly differed from that in the anatomical (0.78, p = 0.003) and historical models (0.72, p < 0.001). The Hosmer-Lemeshow test revealed an adequate fit for all of the models. Additionally, the combined model more accurately reclassified 10.3% (p = 0.044) and 21.9% (p = 0.003) of all of the subjects than either the anatomical or historical model. Internal validation of the combined model by the bootstrapping method showed a fair model performance. Overall performance of combined anatomical and historical findings offers incremental utility in detecting OSA. Results of this study suggest integrating both history and anatomical findings for a screening scheme of pediatric OSA.


Effects of Curcumin on Axon Growth and Myelin Sheath Formation in an In Vitro Model.
Although the beneficial effects of curcumin, extracted from rhizomes of the ginger family genus Curcuma, on the repair and regeneration of nerves have been evaluated in vitro, there are few studies concerning its effects on axon myelination. Here, we used pheochromocytoma cells as an in vitro model of peripheral nerves. Pheochromocytoma cells were cultured alone or cocultured with Schwann cells and treated with increasing concentrations of curcumin. Cell growth was observed, and the expression levels of growth-associated protein 43 (GAP-43), microtubule-associated protein 2 (MAP-2), myelin basic protein (MBP), myelin protein zero (MPZ), Krox-20, and octamer binding factor 6 (Oct-6) were quantified. We found a significant increase in expression of all six proteins following curcumin treatment, with a corresponding increase in the levels of MBP, MPZ, Krox-20, and Oct-6 mRNA. Upregulation was greater with increasing curcumin concentration, showing a concentration-dependent effect. The results suggested that curcumin can promote the growth of axons by upregulating the expression of GAP-43 and MAP-2, stimulate synthesis and secretion of myelin-related proteins, and facilitate formation of the myelin sheath in axons by upregulating the expression of Krox-20 and Oct-6. Therefore, curcumin could be widely applied in future strategies for the treatment of nerve injuries.


RETRACTED: Does Low-Level Laser Photobiomodulation Improve Neurosensory Recovery After Orthognathic Surgery? A Clinical Trial With Blink Reflex.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The article includes material that had already appeared in de Oliveira RF, da Silva AC, Simoes A, Youssef MN, de Freitas PM. Laser Therapy in the Treatment of Paresthesia: A Retrospective Study of 125 Clinical Cases. Photomed Laser Surg. 2015 Aug; 33(8)415-23. doi: 10.1089/pho.2015.38888. PMID:26226172 in the journal Photomedicine and Laser Surgery by Mary Ann Liebert Publishing. Any re-use of any material should be appropriately cited and published with permission of any relevant copyright owner. As such this article represents a misuse of the scientific publishing system. Apologies are offered to readers of the journal that this was not detected during the submission process.


ACE2-IgG1 fusions with improved in vitro and in vivo activity against SARS-CoV-2.
SARS-CoV-2, the etiologic agent of COVID-19, uses ACE2 as a cell entry receptor. Soluble ACE2 has been shown to have neutralizing antiviral activity but has a short half-life and no active transport mechanism from the circulation into the alveolar spaces of the lung. To overcome this, we constructed an ACE2-human IgG1 fusion protein with mutations in the catalytic domain of ACE2. A mutation in the catalytic domain of ACE2, MDR504, significantly increased binding to SARS-CoV-2 spike protein, as well as to a spike variant, in vitro with more potent viral neutralization in plaque assays. Parental administration of the protein showed stable serum concentrations with excellent bioavailability in the epithelial lining fluid of the lung, and ameliorated lung SARS-CoV-2 infection in vivo. These data support that the MDR504 hACE2-Fc is an excellent candidate for treatment or prophylaxis of COVID-19 and potentially emerging variants.


6-[(tert-Butyl-dimethyl-sil-yl)-oxy]-3-ethenyl-7-meth-oxy-4-[(tri-methyl-sil-yl)ethyn-yl]naphtho-[2,3-c]furan-1(3H)-one.
The tricyclic core in the title compound, C26H34O4Si2, shows disorder of the furan ring and deviates slightly from planarity, with the largest displacement from the least-squares plane [0.166 (2) Å] for the major disordered part of the methine C atom. To this C atom the likewise disordered vinyl group is attached, lying nearly perpendicular to the tricyclic core. In the crystal, mutual C-H⋯π inter-actions between the methine group of the furan ring and the central ring of the tricyclic core of an adjacent mol-ecule lead to inversion-related dimers.


Andersen mutations of KCNJ2 suppress the native inward rectifier current IK1 in a dominant-negative fashion.
The Andersen's syndrome is a hereditary disease, which is characterized by cardiac arrhythmias, periodic paralysis and dysmorphic features. Recently, mutations of the KCNJ2 gene, which encodes the inward rectifying potassium channel subunit Kir2.1, have been identified in affected individuals. However, the functional effects of these mutations have not yet been fully elucidated. To clarify this situation we generated known Andersen disease mutants of KCNJ2 which did not yield any measurable K(+) currents in CHO cells indicating that the Andersen mutants failed to form functional homomultimeric complexes. EGFP-tagged KCNJ2 wild-type and mutant channels distributed in a similar homogeneous pattern in the cell membrane suggesting that protein trafficking was not altered by the Andersen mutations but rather implicating that the mutations rendered the KCNJ2 channel non-functional. In heterologous coexpression experiments the Andersen mutants exerted a dominant-negative effect on wild-type KCNJ2. However, the extent of suppression varied between the different KCNJ2 mutants. Given our results in CHO cells, we expressed the disease mutant KCNJ2-S136F in neonate rat cardiomyocytes using adenoviral gene transfer to test the effect of Andersen mutants on native I(K1). I(K1) density was indeed significantly reduced in KCNJ2-S136F-infected cells (n=9) compared to control cells (n=9) over a voltage range from -70 to -150 mV (P<0.05). These results support that Kir2.x channels are a critical component of native I(K1) in neonate rat cardiomyocytes and that a dominant-negative suppression of I(K1) in native cells is the pathophysiological correlate of the Andersen's syndrome.


Binding of nuclear factors to the 5'-interferon consensus sequence of the HLA-A2 class I gene.
To investigate the regulatory role of the conserved interferon consensus sequence (ICS) found in the 5' flanking region of HLA class I genes, we studied the binding of nuclear proteins to the ICS of HLA-A2 gene (ICS-A2) by the gel shift assay. Nuclear extracts from several human cell lines expressing different levels of surface class I molecules reveal an ICS-A2-protein complex of similar mobility, the amount of which varies in a cell type-dependent manner. In some cell lines, interferon-gamma treatment decreased the level of this complex. The overlapping enhancer A element also competes for the formation of this ICS-A2-protein complex. Footprinting and methylation interference analyses demonstrate that nuclear protein(s) protect specific sequences within the ICS-A2 element, suggesting that these protein(s) may represent interferon-sensitive transcription factors.


Pilot study of a social network intervention for heroin users in opiate substitution treatment: study protocol for a randomized controlled trial.
Research indicates that 3% of people receiving opiate substitution treatment (OST) in the UK manage to achieve abstinence from all prescribed and illicit drugs within 3 years of commencing treatment, and there is concern that treatment services have become skilled at engaging people but not at helping them to enter a stage of recovery and drug abstinence. The National Treatment Agency for Substance Misuse recommends the involvement of families and wider social networks in supporting drug users' psychological treatment, and this pilot randomized controlled trial aims to evaluate the impact of a social network-focused intervention for patients receiving OST. In this two-site, early phase, randomized controlled trial, a total of 120 patients receiving OST will be recruited and randomized to receive one of three treatments: 1) Brief Social Behavior and Network Therapy (B-SBNT), 2) Personal Goal Setting (PGS) or 3) treatment as usual. Randomization will take place following baseline assessment. Participants allocated to receive B-SBNT or PGS will continue to receive the same treatment that is routinely provided by drug treatment services, plus four additional sessions of either intervention. Outcomes will be assessed at baseline, 3 and 12 months. The primary outcome will be assessment of illicit heroin use, measured by both urinary analysis and self-report. Secondary outcomes involve assessment of dependence, psychological symptoms, social satisfaction, motivation to change, quality of life and therapeutic engagement. Family members (n = 120) of patients involved in the trial will also be assessed to measure the level of symptoms, coping and the impact of the addiction problem on the family member at baseline, 3 and 12 months. This study will provide experimental data regarding the feasibility and efficacy of implementing a social network intervention within routine drug treatment services in the UK National Health Service. The study will explore the impact of the intervention on both patients receiving drug treatment and their family members. ISRCTN22608399. ISRCTN22608399 registration: 27/04/2012. Date of first randomisation: 14/08/2012.


Production of pectin-whey protein nano-complexes as carriers of orange peel oil.
Orange peel oil is one of the most common flavorings used in the food industry which is volatile under environmental conditions. Encapsulation is the best way to protect it and control its release. One of the nanoencapsulation systems for food bioactive ingredients is complexation method, which entraps the core materials in a complex of two different biopolymers. In this study, orange peel oil was nanoencapsulated by pectin-whey protein nanocomplexes. After determining the optimum nanocomplex suspensions containing orange peel oil based on the stability, viscosity, and color, they were formulated in three different pH values (3, 6 and 9) and converted into powdered forms by freeze drying. The analysis of size and zeta potential of nanocomplexes revealed that the smallest particles formed in pH=6. The encapsulation efficiency of the powders at pH=3, 6 and 9 were 88, 84, and 70%, respectively and there was a reverse linear correlation between encapsulation efficiency and the color index (b*). The microstructure and the morphology of the nanocomplex powders was investigated by SEM and AFM and the results showed that more spherical particles are formed in pH=3. FTIR analysis determined that there was a chemical reaction and bond formation between whey proteins and pectin as a sharp band was appeared in 991cm-1.


Measurements of production cross sections of the Higgs boson in the four-lepton final state in proton-proton collisions at s = 13 TeV.
Production cross sections of the Higgs boson are measured in the H → Z Z → 4 ℓ ( ℓ = e , μ ) decay channel. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV , collected by the CMS detector at the LHC and corresponding to an integrated luminosity of 137 fb - 1 is used. The signal strength modifier μ , defined as the ratio of the Higgs boson production rate in the 4 ℓ channel to the standard model (SM) expectation, is measured to be μ = 0.94 ± 0.07 (stat) - 0.08 + 0.09 (syst) at a fixed value of m H = 125.38 GeV . The signal strength modifiers for the individual Higgs boson production modes are also reported. The inclusive fiducial cross section for the H → 4 ℓ process is measured to be 2 . 84 - 0.22 + 0.23 (stat) - 0.21 + 0.26 (syst) fb , which is compatible with the SM prediction of 2.84 ± 0.15 fb for the same fiducial region. Differential cross sections as a function of the transverse momentum and rapidity of the Higgs boson, the number of associated jets, and the transverse momentum of the leading associated jet are measured. A new set of cross section measurements in mutually exclusive categories targeted to identify production mechanisms and kinematical features of the events is presented. The results are in agreement with the SM predictions.


Ivabradine in heart failure patients with reduced ejection fraction and history of paroxysmal atrial fibrillation.
Ivabradine is indicated for heart failure (HF) patients with reduced ejection fraction (HFrEF), but limited data are available with regards to the use of ivabradine in those with a history of paroxysmal atrial fibrillation (AF). To assess the effect of ivabradine in HFrEF patients with paroxysmal AF, we analysed heart failure (HF) hospitalization and mortality from multiple-centre registry database. We conducted a multicentre observational matched cohort study, and this study enrolled patient with symptomatic HFrEF from 1 January 2015 to 31 December 2018 who had a history of paroxysmal AF in Chang Gung Memorial Hospital medical database in Taiwan. A total of 2042 patients were eligible for the study, of whom 887 were prescribed with ivabradine and 1115 were not. The primary outcome, including HF hospitalization and cardiovascular death, and individual outcome during the 12 month observation period were analysed after inverse probability of treatment weighting. The ivabradine group had significantly lower mean heart rate after 12 months follow-up than the non-ivabradine group (P < 0.05). The primary outcome was significantly higher in the ivabradine group than the non-ivabradine group after 12 months follow-up (hazard ratio [HR] = 1.58; 95% confidence interval [CI], 1.26-2.00, P < 0.001). Moreover, the ivabradine group had a significantly higher event rate of HF hospitalization (HR = 1.56; 95% CI, 1.40-1.75, P < 0.001) and HF death (HR = 1.67; 95% CI, 1.14-2.44, P = 0.009) than the non-ivabradine group. Ivabradine treatment was associated with an increased risk of HF hospitalization in symptomatic HFrEF patients with a history of paroxysmal AF. Further prospective randomized studies are warranted.


Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC.
Dopamine, the major neurotransmitter depleted in Parkinson disease, can be synthesized and regulated in vivo with a combination of intrastriatal AAV-hAADC gene therapy and administration of the dopamine precursor l-Dopa. When tested in MPTP-lesioned monkeys, this approach resulted in long-term improvement in clinical rating scores, significantly lowered l-Dopa requirements, and a reduction in l-Dopa-induced side effects. Positron emission tomography with [(18)F]FMT confirmed persistent AADC activity, demonstrating for the first time that infusion of AAV vector into primate brain results in at least 6 years of transgene expression. AAV-hAADC restores the ability of the striatum to convert l-Dopa into dopamine efficiently. Introduction of this therapy into the clinic holds promise for Parkinson patients experiencing the motor complications that result from escalating l-Dopa requirements against a background of disease progression.


Metastatic infection during Staphylococcus aureus bacteremia.
Staphylococcus aureus causes various infections, including skin and soft tissue infections and pneumonia via both, community-associated and nosocomial infection. These infectious diseases can lead to bacteremia, and may subsequently result in metastatic infections in several cases. Metastatic infections are critical complications in patients with S. aureus bacteremia, since the optimal duration of the antimicrobial treatment differs in patients with and without metastatic infection. Notably, two weeks of antimicrobial treatment is recommended in case of uncomplicated S. aureus bacteremia, whereas in patients with S. aureus bacteremia-associated endocarditis or vertebral osteomyelitis, six weeks of antimicrobial administration is vital. In addition, misdiagnosis or insufficient treatment in metastatic infection is associated with poor prognosis, functional disability, and relapse. Although echocardiography is recommended to examine endocarditis in the patients with S. aureus bacteremia, it remains unclear which patients should undergo additional examinations, such as CT and MRI, to detect the presence of other metastatic infections. Clinical studies have revealed that permanent foreign body and persistent bacteremia are predictive factors for metastatic infections, and experimental studies have demonstrated that the virulence factors of S. aureus, such as fnbA and clfA, are associated with endocarditis; however, these factors are not proven to increase the risk of metastatic infections. In this review, we assessed the incidence, predictive factors, diagnosis, and treatment for metastatic infections during S. aureus bacteremia.


Inhibition of the local Shwartzman reaction by turpentine, prostaglandin E2 and carbon tetrachloride.
The conventional local Shwartzman reaction (LSR) did not occur in rabbits whose plasma haptoglobin (Hp) was lowered by treatment with carbon tetrachloride, nor in animals in whom Hp was elevated after treatment with turpentine, or PGE2 or endotoxin. The possible mechanisms of such inhibition of the LSR are discussed.


Nonomuraea terrinata sp. nov., a novel soil actinomycete.
The taxonomic position of a soil isolate, strain E626, was evaluated using the polyphasic approach. The organism was found to have chemical and morphological features consistent with its assignment to the genus Nonomuraea, a member of the family Streptosporangiaceae. Strain E626 consistently formed a distinct phyletic line within the Streptosporangiaceae 16S rDNA tree using four different algorithms. Furthermore, the taxonomic distinctness of the organism is underpinned by a range of phenotypic properties, notably morphological features. It is, therefore, proposed that the organism be classified in the genus Nonomuraea as Nonomuraea terrinata sp. nov.


Quality assurance in bariatric surgery.
Quality assurance is a function that exists in manufacturing,engineering, and the service industry. Bariatric surgery is an undertaking with a special form of consumer product and service. In this day of limited resources and significant value exchanges among stakeholders (ie, patients, surgeons, third-party payers),the goal of the bariatric community is to deliver quality outcomes with safety, efficacy, and efficiency. The American Society for Bariatric Surgery and the Surgical Review Corporation, in conjunction with the bariatric community, will use quality assurance methods to produce quality outcomes that will satisfy the value exchanges of all stakeholders.


Mid-pregnancy circulating immune biomarkers in women with preeclampsia and normotensive controls.
To determine if mid-pregnancy circulating immune biomarkers are associated with preeclampsia. Nested case-control study of 410 preeclamptic women and 297 normotensive controls with primiparous singleton pregnancies enrolled in the Danish National Birth Cohort. The mean gestational age in our cohort is 16 weeks (range 9-26). Preeclampsia was defined by blood pressure ⩾140/90 mmHg and proteinuria ⩾3 g/24 h. Serum immune biomarkers included interleukin (IL)-6, IL-6 receptor, IL-4, IL-4 receptor, IL-5, IL-12, IL-2, TNF-α, TNF-β, TNF-receptor, IL-1β, IL-1α, IL-8, IL-10, IFN-γ, IL-18, macrophage migration inhibitory factor, macrophage inflammatory protein, transforming growth factor-beta (TGF-β), and RANTES. Associations with preeclampsia, term preeclampsia and preterm preeclampsia were determined using two logistic regression models; (1) biomarkers were dichotomized by the limit of detection (LOD); (2) on the continuous scale, non-detectable values were imputed by LOD/2 and transformed (base 2). All models were adjusted for body mass index and smoking. IL1β was significantly associated with a decrease in the log odds of preeclampsia (p=0.0065), term preeclampsia (p=0.0230) and preterm preeclampsia (p=0.0068). Results were similar for IL4r and preeclampsia (p=0.0383). In the dichotomized models, detectable TNF-β was significantly associated with preeclampsia (ORadj 1.6, 95% CI 1.1-2.3) and term preeclampsia (OR 1.7, 95% CI 1.1-2.5) but not preterm preeclampsia. Detectable IL6 was significantly with term preeclampsia only (OR 1.5, 95% CI 1.1-2.2). Mid-pregnancy circulating IL1β, IL4r, IL6, and TNFβ were associated with preeclampsia. However, results were not consistent across statistical models. As the relationship is complex, future studies should explore cytokine clusters in preeclampsia risk.


The inhibitory effect of a polymerisable cationic monomer on functional matrix metalloproteinases.
This study examined the use of methacryloxylethyl cetyl dimethyl ammonium chloride (DMAE-CB) as a potential matrix metalloproteinases (MMPs) inhibitor on both soluble recombinant and dentine matrix-bound endogenous MMPs, meanwhile attempted to determine the effective anti-MMP group of quaternary ammonium methacrylates (QAMs). The possible inhibitory effects of five DMAE-CB mass concentrations (0.1%, 0.5%, 1%, 3%, 5%) on soluble rhMMP-9 were measured using a colorimetic assay kit. Methyl methacrylate (MMA) and [2-(methacryloyloxy)ethyl] trimethylammonium chloride (METMAC) were also screened against rhMMP-9 to compare the inhibitory effect with DMAE-CB. Matrix-bound endogenous MMP-activity was evaluated in completely demineralized dentine beams. Thirty beams were randomly divided into three groups (N=10) and respectively placed into 500μL of calcium- and zinc-containing media (CM; control), 0.2% chlorhexidine or 3% DMAE-CB in CM aged for 30 days. The changes in modulus of elasticity, loss of dry mass and solubilization of collagen peptides were measured via three-point bending, precision weighing and hydroxyproline assay, respectively. 0.5-5% mass concentrations of DMAE-CB were highly effective (P<0.05) in inhibiting rhMMP-9 varied between 76.56±6.44% and 97.06±3.24%, the inhibitory effect of MMA was much lower than that of METMAC and DMAE-CB at the same concentration (P<0.05). Dentine beams incubated in 3% DMAE-CB showed only a 26.34% decrease in the modulus of elasticity (75.74% decrease in control), a 1.72±1.56% loss of dry mass (29.70±9.12% loss in control), and significantly less solubilized hydroxyproline when compared with the control (P<0.05). DMAE-CB is effective in inhibiting both soluble recombinant MMPs and matrix-bound dentine MMPs. Quaternary ammonium group is the effective anti-MMP group of QAMs. The incorporation of DMAE-CB into dental adhesives has the potential to enhance the durability of dentine bonding and thus increases the longevity of restorations.


Utilization of submandibular ultrasound to measure oral cavity changes with interventions in routine airway management.
Ultrasound is a quick, noninvasive, inexpensive tool that can provide an accurate airway assessment. Tongue thickness, oral cavity height, and their relationship were measured using submandibular ultrasonography with and without oral airway interventions during intubation in 26 patients. The mean tongue thickness to oral cavity height ratio was 0.83 ± 0.03. The percent change of tongue thickness to oral cavity height decreased significantly by 36.47% with an oral airway and by 43.49% with laryngoscope interventions (P < 0.01). This study demonstrates how ultrasound-measured oral cavity ratios change with the placement of airway equipment, and application of these findings may advance our understanding of advanced airway management among diverse patient populations.


Post-Myocardial Infarction Free-Wall Rupture: Rapid Diagnosis and Management.
We present a case of post-myocardial infarction free-wall rupture in a critically ill patient presenting to the emergency department. Through our case we highlight the prompt evaluation, diagnosis, and management necessary to improve survival in a patient with this life-threatening condition. (Level of Difficulty: Beginner.).


Angle-closure: risk factors, diagnosis and treatment.
Primary angle-closure glaucoma (PACG) is the leading cause of blindness in East Asia. The disease can be classified into primary angle-closure suspect, primary angle closure (PAC), and PACG. Pupil-block, anterior nonpupil-block (plateau iris and peripheral iris crowding), lens related and retrolenticular mechanisms have been suggested as the four main mechanisms of angle closure. The risk factors for PAC are female gender, increasing age, Inuit or East Asian ethnicity, shallow anterior chamber, shorter axial length, and genetic factors. The diagnosis of acute PAC is mainly clinical. Diagnosis can be made with careful slit lamp examination, including intraocular pressure (IOP) measurement and gonioscopy. The diagnosis of chronic PAC and chronic PACG also require a careful history to assess risk factors, slit lamp examination including IOP and gonioscopy. Further investigations may also be required including visual fields, ultrasound biomicroscopy, and other imaging methods. In acute PAC, rapid control of the IOP needs to be achieved to limit optic-nerve damage. This can be carried out medically, and/or by laser iridoplasty. Both the affected and fellow eye should undergo laser peripheral iridotomy (PI). The aim of treating chronic PAC is to eliminate the underlying pathophysiological mechanism and to reduce IOP. This can be done by carrying out laser PI, iridoplasty, medical therapy, or surgery (trabeculectomy, lens extraction, combined lens extraction with trabeculectomy and goniosynechialysis). Angle-closure glaucoma is usually an aggressive, visually destructive disease. By assessing the risk factors and diagnosing the mechanism involved in a patient's condition, the management of that patient can be tailored appropriately.


Obstructive sleep apnea: diagnosis, medical management and dental implications.
Patients with undiagnosed obstructive sleep apnea (OSA) represent a major public health problem, and studies suggest that the incidence of OSA may be even higher than estimated. The authors reviewed current literature describing comorbidities of patients with OSA. Sleep medicine is a relatively new field. Dental practitioners may lack educational exposure and, as a result, feel uncomfortable asking their patients sleep-related questions. While patients with well-controlled OSA present few difficulties for routine dental treatment, it is imperative that health care professionals understand the comorbidities associated with OSA and that untreated OSA may contribute to increased morbidity and mortality. Dental professionals have a unique doctor-patient relationship that affords them a role in recognizing sleep disorders by exploring the history of patients who are sleepy.


Mutagenicity of surface soil from residential areas in Kyoto city, Japan, and identification of major mutagens.
To clarify the mutagenic potential of surface soil in residential areas in Kyoto city, surface soil samples were collected twice or three times from 12 sites, and their organic extracts were examined by the Ames/Salmonella assay. Almost all (>92%) samples showed mutagenicity in TA98 without and with S9 mix, and 8/25 (32%) samples showed high (1000-10,000 revertants/g of soil) or extreme (>10,000 revertants/g of soil) activity. Moreover, to identify the major mutagens in surface soil in Kyoto, a soil sample was collected at a site where soil contamination with mutagens was severe and continual. The soil extract, which showed potent mutagenicity in TA98 without S9 mix, was fractionated by diverse column chromatography methods. Five major mutagenic constituents were isolated and identified to be 1,6-dinitropyrene (DNP), 1,8-DNP, 1,3,6-trinitropyrene (TNP), 3,9-dinitrofluoranthene (DNF), and 3,6-dinitrobenzo[e]pyrene (DNBeP) by co-chromatography using high performance liquid chromatography and spectral analysis. Contribution ratios of 1,6-DNP, 1,8-DNP, 1,3,6-TNP, 3,9-DNF, and 3,6-DNBeP to total mutagenicity of the soil extract in TA98 without S9 mix were 3, 10, 10, 10, and 6%, respectively. These nitroarenes were detected in surface soil samples collected from four different residential sites in other prefectures, and their contribution ratios to soil mutagenicity were from 0.7 to 22%. These results suggest that surface soil in residential areas in Kyoto was widely contaminated with mutagens and there were some sites where surface soils were heavily polluted. 1,6-DNP, 1,8-DNP, 1,3,6-TNP, 3,9-DNF, and 3,6-DNBeP may be major mutagenic constituents that contaminate surface soil in Kyoto and other residential areas.


Determinants of ultra-processed food consumption in Brazilian children and adolescents with type 1 diabetes mellitus: a cross-sectional study.
To analyze the determinants of UPP consumption among children and adolescents with type 1 diabetes mellitus. Cross-sectional study at a reference hospital for the treatment of diabetes in Rio de Janeiro, Brazil. The sociodemographic, anthropometric, dietary, and clinical factors associated with the percentage of total energy intake (TEI) consumed in the form of UPP were investigated. Food consumption was assessed by 24 h recall and the foods were classified according to the degree of processing as described in the NOVA classification, after which the TEI of each food group was calculated. Multiple linear regression was adopted in the analysis, and associations with p<0.05 were considered significant. The study included 120 children and adolescents with a mean age of 11.74 ± 2.88 years, 53.3% female. Body mass index z-score was 0.65 (± 0.89) and 31.7% (n=38) were overweight. The average total energy consumption was 1,756.38 kcal (± 518.38). The mean percentage of TEI from UPP was 24.2% ± 17.9, meaning that 425.59 kcal (± 380.15) of all calories ingested came from such foods. The independent variables associated with the percentage of ultra-processed foods (UPP) in TEI were: per capita household income up to one the minimum wage (β: -22.03; CI 95% -35.24 to -8.82); and parents/guardians schooling of the up to nine years in formal education (β: 19.86; CI 95% 8.27-31.45). Lower household income and fewer years in formal education seem to determine a preference for UPP over fresh and minimally processed foods.


David V procedure and hemiarch replacement in a patient with Loeys-Dietz-Syndrome and beta thalassemia minor: a case report.
We report the case of a 36-year-old European female patient presenting with a sinus valsalva aneurysm of 47 mm with moderate aortic regurgitation. Additionally, an aneurysm of the brachiocephalic trunk and multiple aneurysms of the right internal mammary artery were identified. Previous medical history included Loeys-Dietz syndrome (LDS) Type RII due to a TGF-beta receptor mutation, and beta thalassemia minor with a baseline hemoglobin of 9,3 g/dL on admission.Reconstruction of the aortic root and hemiarch replacement was performed in circulatory arrest under moderate hypothermia. During surgery, hypothermia was required as part of the cerebral protection strategy. We aim to highlight special considerations and discuss the effects of cooling, rewarming and the use of cardiopulmonary bypass (CPB) during extensive surgery in a patient with LDS and beta thalassemia minor.


Evaluation of in vitro cytotoxicity and paracellular permeability of intact monolayers with mouse embryonic stem cells.
Mouse embryonic stem (mES) cells were induced to form intact monolayers in cell culture inserts, using combinations of extracellular matrix (ECM) components and growth factors (GFs). Progressive formation of intact monolayers was monitored using transepithelial electrical resistance (TEER) and passage of paracellular permeability (PP) markers. The mES cells were initially inoculated on inactivated mouse embryonic fibroblasts (MEFs) plus leukemia inhibitory factor (LIF). At 75% confluence, cells were passaged in the absence of MEF and LIF to stimulate formation of rounded multicellular aggregates (MA). After 4 days, cultures containing MA were transferred to culture inserts coated with ECM components only, and grown in the presence of selected individual GFs. An additional 10-14 days revealed confluent monolayers with TEER values of 500-700 ohms cm2 (Omega cm2). Monolayers grown on inserts coated with ECM components, such as fibronectin or collagen-IV, in the presence of epidermal growth factor or keratinocyte growth factor in the medium, yielded the highest TEER measurements when compared to cultures grown without GFs or ECM. Acute cytotoxicity (AC) studies with confluent monolayers of mES cells in 96-well plates indicated that there is a high correlation (R2=0.91) between cell viability and TEER for 24-h exposure time. Also, decrease in TEER is inversely proportional with increase in PP of markers. In comparison to standardized Registry of Cytotoxicity (RC) data and TEER measurements, MTT IC50 values for mES cells are lower. Thus, at equivalent concentrations for the same chemicals, cell viability decreases before the integrity of the monolayer is compromised. This system represents a novel approach for the manipulation of mES cells toward specific intact monolayers, as an in vitro model for biological monolayer formation, and most importantly, for applications to cytotoxicity testing.


[Dynamic changes in arylsulfatase activity in the initial period of acute focal myocardial ischemia in an experiment].
The increase in arylsulphatase activity in the ischemic zone has been shown by histochemical method in progressing acute myocardial ischemia. The increase in the enzyme activity in a so-called "intact" zone was less marked.


[Implementing an ERAS protocol].
An orthopaedic surgeon at Clinique Saint-Augustin in Nantes has joined the label developed by the Groupe Francophone de Réhabilitation Améliorée après Chirurgie (Francophone Group for Enhanced Recovery After Surgery. The establishment has taken an interest in this approach and is promoting it by applying the recommendations issued by the Haute Autorité de Santé (French National Health Authority) for this new circuit.


Tightly-bound non-histone proteins in different nucleosome-like subpopulations from pig kidney chromatin.
By differential sucrose gradient centrifugation of pig kidney chromatin in the presence or absence of Na-EDTA and under varying ionic strength conditions, three nucleosome-like subpopulations with different buoyant densities can be obtained. These particles, on the basis of their histones and HMG protein pattern, of the 5-methylcytosine level of their DNA and of the RNA polymerase activity associated with them, can be considered as originating from chromatin fractions differently involved in gene expression. Two-dimensional electrophoresis of the tightly-bound non-histone proteins shows a distinct pattern for each subpopulation, such protein components being notably present in restricted numbers but in high amounts in the subpopulation which was apparently derived from condensed heterochromatin.


Trends in Inequalities in the Use of Condom by Urban Teenagers in Spain.
Social and economic inequalities in condom use by adolescents have been reported previously. Also, condom use has declined during the last decade. The aim of the study was to describe trends in the use of condoms in our setting, and how these trends may differ between socioeconomic groups in boys, and separately in girls, aged 17-19 years attending school in Barcelona between 2004 and 2012. We analyzed data from three annual surveys on risk factors in secondary students, which included a representative sample of the city's population; individuals who had previously had sexual intercourse (n = 1570) were included in the study. We calculated adjusted prevalence ratios (aPR) and their confidence intervals (95% CI) using robust Poisson regression models. The prevalence of condom use among boys was 87.0% in 2004 and 76.2% in 2012, and 76.7 and 64.7% among girls, respectively. This decrease was greater in adolescents with a low socioeconomic level, both in boys (aPR = 0.80) and girls (aPR = 0.84). The observed increase of socioeconomic inequalities in condom use in adolescents highlights a possible deterioration in good sexual practices and policies during the studied period.


High sorption efficiency for As(III) and As(V) from aqueous solutions using novel almond shell biochar.
Arsenic (As) presence in surface reservoirs and groundwater is considered as an extremely alarming issue around the globe. The objectives of the present study were to evaluate the sorption potential of almond shell (ALS) and almond shell biochar (ASB) based sorbents for the removal of As(III)/As(V) from As-contaminated aqueous solutions. The maximum As(III) sorption capacity of ALS and ASB were 4.6 and 4.86 mg g-1, respectively at an initial As concentration of 5 mg L-1, pH ∼ 7.2 and sorbent dose of 0.6 g L-1. Similarly, in case of As(V) the maximum sorption capacities were reported as 3.45 and 3.6 mg g-1 by ALS and ASB respectively. Almond shell biochar removed 10-25% higher As(III)/As(V) compared to the ALS. The isotherm modeling results revealed that both for As(III) and As(V), Langmuir model presented the suitable fit to the equilibrium data compared to other model showing the monolayer sorption to be a dominant sorption mechanism. The FTIR and XPS spectroscopy revealed that mostly -OH functional groups along with some other aromatic and/or aliphatic carbon- and oxygen-rich groups (CC-C, -C-H, CO) were responsible for As sorption by both sorbents. It is concluded that ASB can remove As, notably As(III) from water more efficiently compared to natural ALS. Overall, the results of this research reveal that biochar conversion of ALS can enhance the sorption capacity for As in contaminated waters such as drinking water and wastewater.


Parental predictors of pediatric panic disorder/agoraphobia: a controlled study in high-risk offspring.
Our objective was to evaluate parental risk factors for pediatric-onset panic disorder/agoraphobia (PD/AG) in offspring at high risk for PD/AG. Comparisons were made between parents with PD who had a child with PD or AG (N = 27) and parents with PD without children with PD or AG (N = 79). Comparisons were also made between the spouses of these parents with PD. Separation anxiety disorder, social phobia, obsessive-compulsive disorder, and bipolar disorder in the parents with PD and their spouses accounted for the risk for childhood onset PD/AG in the offspring. This risk was particularly high if both parents were affected with social phobia. These findings suggest that psychiatric comorbidity with other anxiety disorders and with bipolar disorder in parents with PD and their spouses confer a particularly high risk in their offspring to develop PD/AG in childhood.


Differential effect of acute and chronic haloperidol administration on dopamine turnover in rat nigrostriatal and retinal dopaminergic neurons.
Haloperidol-induced increases in DOPAC and HVA declined in the striatum but remained unchanged in the retina after chronic pretreatment with haloperidol (1-4 weeks). DA concentrations were unaffected in the striatum but decreased in the retina after acute or chronic haloperidol administration. Light stimulation increased both retinal DA and DOPAC. The findings indicate that acute and chronic haloperidol affect nigrostriatal and retinal DA neurons differentially. In addition, DA neurons in retina respond differently to activations by haloperidol and light.


Lessons about the reliability of congenital syphilis and vertical HIV transmission data learned from case reviews in Uruguay: a cross-sectional study.
In Uruguay it is mandatory to review all cases of positive HIV or reactive syphilis tests in pregnancy and peripartum. We compared the rates of mother-to-child transmission of syphilis and HIV detected by case reviews to those obtained from the usual surveillance system and described the characteristic of vertical transmission cases. This is a cross-sectional study performed with secondary data obtained from official government sources, for all the country cases of maternal to child transmission of HIV and syphilis from 2012 to 2017, with descriptive analyses. For congenital syphilis analyses, the following pregnancy characteristics were investigated: number of antenatal checks, gestational age at pregnancy diagnosis, gestational age at syphilis test and diagnosis, adequate treatment, and treatment of partners. Sociodemographic characteristics included type of health care (public/private), maternal age, distribution of ethnic minorities, maximum educational attainment, presence of partner, planned pregnancy, drug and alcohol use, domestic violence, previous maternal diagnosis of syphilis, and previous children with congenital syphilis. Coverage of syphilis case reviews increased from 82% in 2014 to 97.4% in 2017. For HIV, this coverage reached 100% in 2017 and elimination of mother to child transmission was achieved. A marked decline in congenital syphilis was noted in the public health care sector, especially in the capital Montevideo, whereas the private sector has remained below the elimination target. Variables related with congenital syphilis in exposed children were late pregnancy diagnosis, < 5 antenatal checks, delayed diagnosis of gestational syphilis, lower rate of correct treatment for gestational syphilis, untreated partner, low maternal schooling, unplanned pregnancy, history of syphilis, and having other children with syphilis. The use of case reviews provided knowledge regarding the accurate number of mother-to-child transmission cases and the evolution of elimination of mother to child transmission in the country. The results suggest that rates must be adjusted, providing an opportunity to improve the reliability of surveillance data, and point the need to address specific gaps in order to improve the quality of care during pregnancy, delivery, and the neonatal period.


Precursor-directed biosynthesis of 6-deoxyerythronolide B analogs in Streptomyces coelicolor: understanding precursor effects.
A fermentation process employing precursor-directed biosynthesis is being developed for the manufacture of 6-deoxyerythronolide B (6-dEB) analogues. Through a plasmid-based system in Streptomyces coelicolor, 6-dEB synthesis is catalyzed by 6-dEB synthase (DEBS). 6-dEB synthesis is abolished by inactivation of the ketosynthase (KS) 1 domain of DEBS but can be restored by providing synthetic activated diketides. Because of its inherent catalytic flexibility, the KS1-deficient DEBS is capable of utilizing unnatural diketides to form various 13-substituted 6-dEBs. Here we characterize process variables associated with diketide feeding in shake-flask experiments. 13-R-6-dEB production was found to depend strongly on diketide feed concentrations, on the growth phase of cultures at feeding time, and on the R-group present in the diketide moiety. In all cases a major portion of the fed diketides was degraded by the cells.


Application of pharmacological principles to benzodiazepine therapy.
The benzodiazepines are a group of drugs which have recently received considerable adverse publicity from within the media, much of which is undeserved. It is not unusual for drugs to produce these strong reactions from within both the professional and the general community. This paper examines the validity of the benzodiazepines in clinical practice and suggests rational guidelines for their continued use based on the clinical pharmacology of the compounds concerned.


Effect of Feeding 0.8% Dried Powdered Chlorella vulgaris Biomass on Growth Performance, Immune Response, and Intestinal Morphology during Grower Phase in Broiler Chickens.
An experiment was performed to study the effects of a low inclusion level of Chlorella vulgaris (CV) biomass in broiler diets on performance, immune response related to inflammatory status, and the intestinal histomorphology. The study was performed with 120 Ross 308 male broiler chickens from 0−35 days of age. The broilers were housed in 12 floor pens (1.5 m2) bedded with wood shavings. The broilers received a three phase diet program, either with 0.8% CV biomass (CV) or without CV (CON). Each diet program was replicated in six pens. The final body weight increased (p = 0.053), and the feed conversion ratio (FCR), corrected for body weight, was reduced (p = 0.02) in birds fed CV compared to birds fed CON. In addition, decreased haptoglobins (p = 0.02) and interleukin-13 (p < 0.01) responses were observed during the grower phase of birds fed CV compared to the birds fed CON. A strong correlation (r = 0.82, p < 0.01) was observed between haptoglobin response and FCR. Histomorphology parameters of the jejunum were not different between the groups. It was concluded that the inclusion of 0.8% CV biomass in broiler diets is effective in influencing immune responses related to inflammatory status and promoting broiler growth.


Single agent rituximab in patients with follicular or mantle cell lymphoma: clinical and biological factors that are predictive of response and event-free survival as well as the effect of rituximab on the immune system: a study of the Swiss Group for Clinical Cancer Research (SAKK).
Predictive factors of rituximab efficacy and its effect on the immune system are still not defined. Three hundred and six patients with follicular or mantle cell lymphoma received four weekly doses of rituximab (induction) and no further treatment (arm A) or four more doses at 2-month intervals (arm B). Response rate to induction was 44%. Independent predictive factors for response were disease bulk <5 cm, follicular histology, normal hemoglobin and low lymphocyte count. Factors associated with event-free survival (EFS) were having responded to induction, having received not more than one line of therapy, Ann Arbor stage I-III, high lymphocyte count, disease bulk <5 cm, Fc-gamma receptor genotype VV and receiving prolonged treatment. B cells were suppressed by treatment but recovered after a median of 12 months in arm A and 18 months in arm B. The median IgM level after 1 year was normal in arm A but was decreased to 73% of baseline in arm B. We observed 24 serious adverse events, equally distributed between arms. Ten patients receiving induction only and six patients receiving prolonged treatment developed a second tumor. We defined the characteristics predicting response and EFS to rituximab. Prolonged treatment results in longer EFS at the cost of a longer reduction in B cell and IgM levels, but without additional clinical toxicity.


Left atrial appendage function analyzed by tissue Doppler imaging in mitral stenosis: effect of afterload reduction after mitral valve commissurotomy.
This study sought to investigate the relative load dependence of left atrial appendage (LAA) tissue Doppler velocities in patients with mitral stenosis after percutaneous mechanical mitral commissurotomy (PMMC). LAA tissue Doppler velocities were obtained in 34 patients with mitral stenosis (20 with sinus rhythm and 14 with atrial fibrillation) before and after PMMC by transesophageal echocardiography. Standard ultrasound studies were also performed for mitral valve orifice area, transmitral pressure gradient, and LAA blood flow velocity measurements. PMMC resulted in a significant increase in mitral valve area (P < .001) and decrease in mean transmitral pressure gradient (P < .001). LAA tissue Doppler velocities consisted of a triphasic velocity profile: SLAA and ELAA occurring during left ventricular contraction and relaxation, respectively, and ALAA occurring after the atrial contraction. After PMMC, ELAA and ALAA velocities consistently increased (4.8 +/- 1.2 to 7.9 +/- 2.6 cm/sec [P < .001] and 6.6 +/- 2.9 to 8.1 +/- 4.2 cm/sec [P < .05], respectively). The mean transmitral pressure gradient was significantly correlated with ALAA before and after PMMC (r = .65). In mitral stenosis, tissue Doppler velocities illustrated improvement of regional LA function after PMMC, in relation to decreased transmitral pressure gradient.


Eagle's syndrome - A case report and review of the literature.
Eagle's syndrome (ES) occurs when an elongated styloid process or calcified stylohyoid ligament causes recurrent throat pain or foreign body sensation, dysphagia, or facial pain. Additional symptoms may include neck or throat pain with radiation to the ipsilateral ear. The symptoms related to this condition can be confused with those attributed to a wide variety of facial neuralgias. ES can be diagnosed radiologically and by physical examination. The treatment of ES is primarily surgical. The styloid process can be shortened through an intraoral or external approach. In this paper a case of ES exhibiting unilateral symptoms with bilateral elongation of styloid process is reported and the literature is reviewed.


Changes in terpene biosynthesis and submergence tolerance in cotton.
Flooding is among the most severe abiotic stresses in plant growth and development. The mechanism of submergence tolerance of cotton in response to submergence stress is unknown. The transcriptome results showed that a total of 6,893 differentially expressed genes (DEGs) were discovered under submergence stress. Gene Ontology (GO) enrichment analysis showed that DEGs were involved in various stress or stimulus responses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs related to plant hormone signal transduction, starch and sucrose metabolism, glycolysis and the biosynthesis of secondary metabolites were regulated by submergence stress. Eight DEGs related to ethylene signaling and 3 ethylene synthesis genes were identified in the hormone signal transduction. For respiratory metabolism, alcohol dehydrogenase (ADH, GH_A02G0728) and pyruvate decarboxylase (PDC, GH_D09G1778) were significantly upregulated but 6-phosphofructokinase (PFK, GH_D05G0280), phosphoglycerate kinase (PGK, GH_A01G0945 and GH_D01G0967) and sucrose synthase genes (SUS, GH_A06G0873 and GH_D06G0851) were significantly downregulated in the submergence treatment. Terpene biosynthetic pathway-related genes in the secondary metabolites were regulated in submergence stress. Regulation of terpene biosynthesis by respiratory metabolism may play a role in enhancing the tolerance of cotton to submergence under flooding. Our findings showed that the mevalonate pathway, which occurs in the cytoplasm of the terpenoid backbone biosynthesis pathway (ko00900), may be the main response to submergence stress.


Challenges to the development of bryostatin-type anticancer drugs based on the activation mechanism of protein kinase Cδ.
Protein kinase C (PKC) isozymes are widely recognized as targets for anticancer therapy, and recent investigations demonstrated that PKC activators are potential therapeutic candidates for Alzheimer's disease and acquired immune deficiency syndrome. However, concerns exist about their therapeutic uses because most PKC activators are potent tumor promoters. Bryostatin 1 (bryo-1) is a unique PKC activator with little tumor-promoting activities. Bryo-1 is currently undergoing clinical trials for the treatment of cancer. However, its limited availability from natural sources and difficulty in the synthesis hamper further studies on its mode of action and structural optimization. Although excellent practical methods for synthesizing several bryo-1-related compounds have been developed, the identification of synthetically more accessible compounds with bryo-1-like activity also provides a promising way to circumvent the problem of supply. The authors focused on the bryo-1's unique mechanism of activating PKCδ that plays a tumor suppressor role, and found that a simple and less lipophilic analogue (aplog-1) of the tumor-promoting aplysiatoxin showed PKCδ-activating behavior similar to bryo-1. Aplog-1 was easily synthesized in only 22 steps using standard reactions. Moreover, its tumor-promoting activity in vitro was very weak, and its cell growth-inhibitory activities were comparable to those of bryo-1. These data suggest that aplog-1 could become another therapeutic lead for cancer.


Influence of external insert angle on structural deformation of long pipe shed with shallow hole.
The long pipe shed advanced support has the characteristics of large construction difficulty, wide support range, and easy deviation. The difference in construction dip angle will produce a different plastic zone of surrounding rock and supporting effects, and the rationality of advanced support design plays an important role in the safety of tunnel opening excavation. Based on the Tianshan Tunnel project, this paper aims at the problems of the loose pebble layer structure, poor cohesion, strong permeability, shallow excavation is not easy to form a confined arch, and easy to causes surrounding rock deformation and failure. Combined with the new method theory, the finite difference software FLAC3D was used to simulate seven excavation schemes of the shallow tunnel entrances. The mechanism and effect of advance support and the influence of construction angle on support effect are analyzed, and the simulation values are compared with the measured data. The results show that using long pipe shed advanced support can effectively reduce the disturbance of excavation to lose pebble rock mass and reduce the convergence value of surrounding rock. The plastic zone of surrounding rock produced by different angles can be divided into three parts. The structural stability difference of the C1 zone is small, and that of the C3 zone is large. The bending moment, shear force, and shape variables of the pipe shed decrease with the increase of the dip angle, while the axial force increases with the increase of the dip angle. According to the similarity between the simulated curve and the measured curve, the best supporting effect can be achieved when the dip angle of the pre-supporting pipe shed is set in the range of 0° ~ 3°.


Skeletal tissue growth, differentiation and mineralization in the NASA rotating wall vessel.
The NASA Rotating Wall Vessel (RWV) is a device that creates a unique environment that supports three-dimensional tissue growth, a heightened level of cell differentiation and randomizes the position of the downward gravitational force on cells. Embryonic bone formation encompasses a cascade of chondrogenic and osteogenic events, which can be altered by changes in gravitational loading. These studies were conducted to determine if the chondrogenic cascade in bone formation would be enhanced or hindered in the unique culture environment of the RWV. Embryonic mouse pre-bone tissues were placed in the RWV at one of four different stages of chondrogenesis, ranging from undifferentiated mesenchyme cells to chondrocytes on the verge of undergoing terminal chondrocyte differentiation. After culture, tissues were analyzed for their size, the amount of alkaline phosphatase (ALP) activity and their ability to form a mineralized matrix. Tissue consisting of cells at the early phase of chondrogenesis grew very little and did not differentiate or mineralize when cultured in the RWV. Some tissues were cultured for short periods in the RWV then cultured in standard culture dishes (SCD). Following this culture regime, the cartilage grew only a small amount, but alkaline phosphatase activity increased, and some mineralized regions formed. The pattern of mineralization was abnormal, with two mineralized zones at each end of the cartilage instead of a single central zone. Tissues that were at the three more advanced stages of chondrogenesis when placed in the RWV showed substantial growth, differentiation and mineralization. Mineralization patterns in these older tissues was normal. Tissues at the oldest stage of chondrogenesis showed more growth and as much or more mineralization as tissue cultured only in SCD. These data suggest that exposure to the RWV at early stages of chondrogenesis severely limits the ability for cartilage growth and yields abnormal downstream morphogenesis. However, at later stages of chondrogenesis, the RWV environment may be beneficial and enhance growth and development. Future studies to characterize intercellular signaling molecules and gene expression activities of chondrocytes in the RWV will be valuable for understanding the mechanism of skeletogenesis.


Immunosensing procedures for carcinoembryonic antigen using graphene and nanocomposites.
Two-dimensional (2D) graphene, sp2-hybridized carbon, and its two major derivatives, graphene oxide (GO) and reduced graphene oxide (rGO) have played an important role in immunoassays (IAs) and immunosensing (IMS) platforms for the detection of carcinoembryonic antigen (CEA), an implicated tumor biomarker found in several types of cancer. The graphene family with high surface area is functionalized to form stable nanocomposites with gold nanoparticles (AuNPs) and electron mediators. The capture anti-CEA antibody (Ab) with high density can be anchored on AuNPs of such composites to provide remarkable detection sensitivity, significantly below the level found in normal subjects and cancer patients. Electrochemical and fluorescence/chemiluminescence-quenching properties of graphene-based nanocomposites are exploited in various detection schemes. Future endeavors are envisioned for the development of an array platform with high-throughput for CEA together with other tumor biomarkers and C-reactive protein, a universal biomarker for infection and inflammation. The ongoing efforts dedicated to the replacement of a lab-based detector by a cellphone with smart applications will further enable cost-effective and frequent monitoring of CEA in order to establish its clinical relevance and provide tools for real-time monitoring of patients during chemotherapy.