Sodium-dependent and -independent transport of L-glutamate in the rat intestinal crypt-like cell line IEC-17.
Mechanisms of L-glutamate transport in intestinal crypts were investigated using the rat intestinal crypt-like cell line IEC-17. Kinetic analysis and competition experiments run in the presence or in the absence of extracellular sodium indicate that L-glutamate uptake occurs through three different transport components: (1) a high affinity Na+-independent component also carrying cystine, similar to system x(c)-; (2) a high affinity Na+-dependent component inhibited by D- and L-aspartate corresponding to the ubiquitous system X(A,G)-; and (3) a low affinity Na+-dependent system resembling the neutral amino acid transport system ASC. The simultaneous presence of these three components suggest that crypt cells are ready to face potential high variations of L-glutamate concentration in the intestinal villus environment.


Mitral valve repair in a patient with acromegaly: case report.
A 61-year-old woman had acromegaly associated with mitral regurgitation (MR) resulting from prolapse of the posterior mitral leaflet. At the age of 51 years, the patient was diagnosed with hypertension and a cardiac murmur. She had the characteristic acromegalic appearance, but without visual disturbance. Blood chemistry revealed an elevated plasma concentration of growth hormone and glucose intolerance. Echocardiography showed remarkable dilation of the left ventricle and prolapse of the anterolateral commissure with severe MR. Magnetic resonance imaging of the brain revealed a pituitary microadenoma. MR was successfully corrected by quadrangular resection of the posterior leaflet, including the prolapsed portion, and prosthetic ring annuloplasty. The patient recovered uneventfully.


Lignin-Based Polymer Electrolyte Membranes for Sustainable Aqueous Dye-Sensitized Solar Cells.
In the quest for sustainable materials for quasi-solid-state (QS) electrolytes in aqueous dye-sensitized solar cells (DSSCs), novel bioderived polymeric membranes were prepared in this work by reaction of preoxidized kraft lignin with poly(ethylene glycol)diglycidylether (PEGDGE). The effect of the PEGDGE/lignin relative proportions on the characteristics of the obtained membranes was thoroughly investigated, and clear structure-property correlations were highlighted. In particular, the glass transition temperature of the materials was found to decrease by increasing the amount of PEGDGE in the formulation, indicating that polyethylene glycol chains act as flexible segments that increase the molecular mobility of the three-dimensional polymeric network. Concurrently, their swelling ability in liquid electrolyte was found to increase with the concentration of PEGDGE, which was also shown to influence the ionic transport efficiency within the membrane. The incorporation of these lignin-based cross-linked systems as QS electrolyte frameworks in aqueous DSSCs allowed the preparation of devices with excellent long-term stability under UV-vis light, which were found to be superior to benchmark QS-DSSCs incorporating state-of-the-art carboxymethylcellulose membranes. This study provides the first demonstration of lignin-based QS electrolytes for stable aqueous DSSCs, establishing a straightforward strategy to exploit the potential of lignin as a functional polymer precursor for the field of sustainable photovoltaic devices.


Attitudes Toward Cancer and Cancer Patients in an Urban Iranian Population.
Because of the significant incidence and mortality of cancer in Iran, a Comprehensive National Cancer Control Program for the prevention and early detection of cancer was launched in 2007. However, cancer awareness and screening rates in Iran did not improve. This study aimed to evaluate public attitudes toward cancer and cancer patients in Iran. We conducted a cross-sectional survey among 953 non-institutionalized individuals in Isfahan, Iran, from November 2014 to February 2015. We collected data on attitudes toward cancer in three domains (impossibility of recovery, cancer stereotypes, and discrimination), as well as questions on willingness to disclose a cancer diagnosis. Among all participants, 33.9% agreed that it is very difficult to regain one's health after a cancer diagnosis, 17.4% felt uncomfortable with a cancer patient, and 26.9% said that they would avoid marrying people whose family members had cancer. While 88.9% of study participants said that cancer patients deserve to be protected in society, 53.3% and 48.4% of participants agreed that they would not disclose a cancer diagnosis to neighbors and coworkers, respectively. Negative attitudes with respect to impossibility of recovery and discrimination toward cancer and cancer patients were common among urban Iranians. Most people would not disclose a cancer diagnosis to others in spite of advancements in cancer diagnosis and treatment, reflecting unfavorable attitudes toward cancer and cancer patients in society. Successful implementation of cancer awareness and prevention programs in Iran may require social changes based on adequate information on cancer and cancer patients. Public attitudes toward cancer and cancer patients are an important factor affecting cancer control programs as well as quality of life and recovery of cancer patients. The issue has not been studied in Iran and the surrounding countries in the Middle East. This is the first report presented on the subject. These findings can be used by health policy makers, health managers, and clinicians for better practice.


Crohn's disease after gastric bypass surgery.
Bariatric surgery for the treatment of severe obesity has increased dramatically in recent years in the USA and parts of Western Europe. The most commonly used technique is the Roux-en Y gastric bypass (RYGBP). Several nutritional and gastrointestinal complications after bariatric surgery have been described during the last 10 years. The authors present two patients with diarrhoea and malnutrition; one after RYGBP and the other after jejunoileal bypass surgery. These patients were subsequently diagnosed with Crohn's disease.


Roll-printed organic thin-film transistor using patterned poly(dimethylsiloxane) (PDMS) stamp.
The roll-printed gate, source, and drain electrodes of organic thin-film transistors (OTFTs) were fabricated by gravure printing or gravure-offset printing using patterned poly(dimethylsiloxane) (PDMS) stamp with various channel lengths and low-resistance silver (Ag) pastes on flexible 150 x 150 mm2 plastic substrates. Bottom-contact roll-printed OTFTs used polyvinylphenol (PVP) as polymeric dielectric and bis(triisopropyl-silylethynyl) pentacene (TIPS-pentacene) as organic semiconductor; they were formed by spin coating or ink-jetting. Depending on the choice of roll-printing method, the printed OTFTs obtained had a field-effect mobility of between 0.08 and 0.1 cm2/Vs, an on/off current ratio of between 10(4) and 10(5), and a subthreshold slope of between 1.96 and 2.32 V/decade. The roll-printing using patterned PDMS stamp and soluble processes made it possible to fabricate a printed OTFT with a channel length of between 12 to 74 microm on a plastic substrate; this was not previously possible using traditional printing techniques. The proposed fabrication process was 20 steps shorted than conventional fabrication techniques.


Length of Acute-Care Hospitalization in Alzheimer's Disease.
The authors conducted a retrospective study of acute-care hospitalization over a 2-year period for patients diagnosed with Alzheimer's disease (AD). These patients were compared to an age- and gender-matched group of non-AD patients. AD patients had fewer admissions and fewer comorbid medical diagnoses, but had a significantly longer total length of hospital stay. Possible explanations for the increased length of stay and suggestions for further research are discussed.


Efficacy and safety of surgery for spontaneous pneumothorax in elderly patients.
There is no clear consensus on the surgical indications for spontaneous pneumothorax in elderly patients. In this study, we aimed to assess the efficacy and safety of surgical treatment of spontaneous pneumothorax in patients aged ≥70 years. We also sought to identify the risk factors for postoperative prolonged air leaks and complications in such patients. Data pertaining to 104 elderly patients who underwent surgery out of 206 patients (aged ≥70 years) who were diagnosed with spontaneous pneumothorax at our institution between 1994 and 2018 were retrospectively reviewed. The incidences of postoperative persistent air leaks (≥2 days) and postoperative complications (≥grade 3; Clavien-Dindo classification) were analysed for efficacy and safety assessment, respectively. Median postoperative air leaks continued for 0 days (range 0-25); 14.4% patients developed ≥grade 3 postoperative complications. On the basis of results of multivariable analysis, it was observed that a higher PaCO2 level was significantly associated with prolonged postoperative air leaks [odds ratio (OR) 1.08, 95% confidence interval (CI) 1.00-1.17; P = 0.047]. Poorer performance status was associated with a significantly increased risk of postoperative complications, as assessed by multivariable analysis (OR 6.13, 95% CI 1.38-27.3; P = 0.017). The recurrence rate was 4.8%; mortality rate of patients was 2.9%. Three-year survival rate after surgery was 73.8%. Surgical treatment of spontaneous pneumothorax may be effective and safe in selected elderly patients. Moreover, higher PaCO2 and poorer performance status were independent risk factors for postoperative persistent air leaks and complications, respectively.


Sediment toxicity of a rapidly biodegrading nonionic surfactant: Comparing the equilibrium partitioning approach with measurements in pore water.
The equilibrium partitioning theory (EqP) assumes that the toxicity of nonionic surfactants in sediment can be predicted from water-only toxicity data as long as the effect concentrations are properly normalized for chemical activity. Therefore, in marine sediment toxicity tests with the model alcohol ethoxylate (AE), C12EO8, freely dissolved concentrations were both measured via solid-phase microextraction and predicted using sorption coefficients. In fully equilibrated test systems (including the overlying water), both methods showed that concentrations in the pore water of the spiked sediment layer causing 50% mortality (LC50) to the amphipod Corophium volutator were in the same range as LC50 values for amphipods exposed to AE in seawater only. In the sediment systems, AE concentrations in the pore water remained constant up to 15 days, while concentrations in the water overlying the sediment decreased to less than 1% of initial concentrations within 6 days due to biodegradation. In such disequilibrated test systems, C. volutator survived pore water dissolved concentrations that were above the LC50. Apparently, this burrowing amphipod is able to exploit the low chemical activity in the overlying water as a refuge from sediment exposure.


Ordering patterns, collection, transport, and screening of sputum cultures in a community hospital: evaluation of methods to improve results.
The clinical usefulness of sputum cultures depends on the quality of specimens submitted to the laboratory. In a community hospital, during two separate surveillance periods, we evaluated ordering practices and circumstances under which sputum specimens were obtained and techniques to improve the quality of the specimens. Physicians themselves rarely participated in obtaining specimens of sputum, and members of the nursing staff directly instructed patients or supervised specimen collection in only one third of cases. The mean elapsed time from collection at the bedside to processing in the laboratory was two hours, with a range from several minutes to 13 hours. One fifth of all the specimens in this study were obtained from patients with no discernible evidence of lower respiratory tract infection. Microscopic screening revealed that one half of the specimens were of poor or uncertain quality. After the first survey, inservice education of nursing personnel in the proper techniques of sputum collection, along with regular use of the screening procedure in the clinical laboratory, failed to effect any long-term change in ordering patterns or collection practices. However, the screening procedure did improve the quality of the sputum cultured, through rejection of unsatisfactory specimens.


Sample training based wildfire segmentation by 2D histogram θ-division with minimum error.
A novel wildfire segmentation algorithm is proposed with the help of sample training based 2D histogram θ-division and minimum error. Based on minimum error principle and 2D color histogram, the θ-division methods were presented recently, but application of prior knowledge on them has not been explored. For the specific problem of wildfire segmentation, we collect sample images with manually labeled fire pixels. Then we define the probability function of error division to evaluate θ-division segmentations, and the optimal angle θ is determined by sample training. Performances in different color channels are compared, and the suitable channel is selected. To further improve the accuracy, the combination approach is presented with both θ-division and other segmentation methods such as GMM. Our approach is tested on real images, and the experiments prove its efficiency for wildfire segmentation.


Large T-cell extradural lymphoma with concurrent marked cerebrospinal fluid eosinophilia in a dog.
A 3-year-old male pit bull terrier was presented for a 4-day history of progressive tetraparesis and cervical pain. Magnetic resonance imaging confirmed an extradural mass within the left lateral vertebral canal extending from caudal C5 to mid-T2. Lumbar cerebrospinal fluid (CSF) demonstrated marked (90%) eosinophilic inflammation. A C6-7 dorsal laminectomy and C7-T2 left hemilaminectomy were done, with gross disease remaining. Histopathology revealed a large T cell lymphoma with marked eosinophilic infiltration. The dog underwent CHOP-based chemotherapy with resolution of clinical signs, with a similar course of therapy performed at recurrence 37 months after initial presentation. The dog was euthanized 39 months after presentation for multiorgan failure secondary to neutropenic sepsis and aspiration pneumonia. This represents a positive long-term response to multimodal treatment of extradural T-cell lymphoma within the vertebral canal associated with a marked CSF eosinophilia.


Vancomycin-induced histamine release and "red man syndrome": comparison of 1- and 2-hour infusions.
Vancomycin-induced "red man syndrome" (RMS) is mediated in part by histamine release, and its severity is correlated with the area under the plasma histamine concentration-time curve. Ten adult male volunteers participated in a randomized, double-blind, two-way crossover trial (1-week washout interval between regimens) to determine the effect of 1- and 2-h infusions of vancomycin (1.0 g) on histamine release and on the frequency and severity of RMS. The severity of RMS was classified a priori as mild, moderate, or severe from a combined score of pruritus and extent of erythema. Serial concentrations of histamine in plasma and concentrations of vancomycin in serum were measured at baseline and during and after each infusion. Of 10 subjects, 8 had evidence of RMS during the 1-h infusion (3 mild, 3 moderate, and 2 severe), whereas only 3 of the 10 subjects (all mild) had RMS during the 2-h infusion (P less than 0.05). The 1-h infusion was associated with a significantly greater peak concentration of histamine in plasma (1.8 +/- 0.7 versus 1.0 +/- 0.3 ng/ml, P = 0.004) and a greater total release of histamine (74.3 +/- 54.1 versus 36.4 +/- 22.6 ng.min/ml, P = 0.017) than was the 2-h infusion. These data suggest that administration of vancomycin over 2 h reduces the frequency and severity of RMS and the amount of histamine released compared with those after a 1-h infusion in healthy volunteers.


Lessons from the first dorsal fin in atheriniforms-A new mode of dorsal fin development and its phylogenetic implications.
The median fins in extant actinopterygians are the product of millions of years of evolution. During this time, different developmental patterns for the dorsal and anal fins emerged leading to a high variation in median fin morphology and ontogeny. In this study, the development of anal and dorsal fins in atheriniforms is described and its consequences for the current phylogenetic hypothesis are discussed. Developmental series of five atheriniform species were investigated using clearing and staining as well as antibody staining. The skeletal elements of the second dorsal fin and the anal fin emerge in a bidirectional pattern. The first dorsal fin, however, arises separately in front of the second dorsal fin after this one is almost completely formed. The pterygiophores of the first dorsal fin, including the interdorsal pterygiophores, develop from caudal to rostral, but the fin-spines of the first dorsal fin form in the opposite direction. This new mode of fin development has been found in all examined atheriniform species with two dorsal fins. Several morphological characters of atheriniforms, including interdorsal pterygiophores, are also found in one other taxon: the Mugiliformes. Thus, several dorsal fin characteristics may provide evidence for a closer relationship of these two taxa.


Monoamine oxidase inhibitory constituents of propolis: kinetics and mechanism of inhibition of recombinant human MAO-A and MAO-B.
Propolis is the resinous material that bees gather from leaf buds, flowers and vegetables. Propolis extracts contain constituents with a broad spectra of pharmacological properties and are important ingredients of popular dietary supplements. Propolis extracts were evaluated in vitro for inhibition of recombinant human monoamine oxidase (MAO)-A and MAO-B. The dichloromethane extract of propolis showed potent inhibition of human MAO-A and MAO-B. Further fractionation identified the most active fractions as rich in flavonoids. Galangin and apigenin were identified as the principal MAO-inhibitory constituents. Inhibition of MAO-A by galangin was about 36 times more selective than MAO-B, while apigenin selectivity for MAO-A vs. MAO-B was about 1.7 fold. Apigenin inhibited MAO-B significantly more potently than galangin. Galangin and apigenin were further evaluated for kinetic characteristics and the mechanism for the enzymes' inhibition. Binding of galangin and apigenin with MAO-A and -B was not time-dependent and was reversible, as suggested by enzyme-inhibitor binding and dissociation-dialysis assay. The inhibition kinetics studies suggested that galangin and apigenin inhibited MAO-A and -B by a competitive mechanism. Presence of prominent MAO inhibitory constituents in propolis products suggests their potential for eliciting pharmacological effects that might be useful in depression or other neurological disorders. The results may also have important implications in drug-dietary supplement interactions.


An open trial of auricular acupuncture for the treatment of repetitive self-injury in depressed adolescents.
Repetitive self-injurious behavior (SIB) is frequently seen in depressed adolescents. In addition to it providing relief for dysphoric symptoms there is evidence of an addictive component to this behaviour. Because auricular acupuncture (AA) has been shown to be effective as an adjunct treatment to cocaine dependence, we wished to test the feasibility and potential efficacy of this treatment in depressed adolescents with repetitive SIB. Our pilot results suggest that AA is an acceptable treatment in this group and that it may be an effective adjunct treatment for repetitive SIB. Moreover, decreases in SIB were evident while depressive symptoms remained unchanged.


Functional domains of the mouse beta3-adrenoceptor associated with differential G protein coupling.
Alternative splicing of mouse beta3-adrenoceptor transcripts produces an additional receptor isoform (beta3b-adrenoceptor) with a C terminus comprising 17 amino acids distinct from the 13 in the known receptor (beta3a-adrenoceptor). We have shown that the beta3b-adrenoceptor couples to both Gs and Gi, whereas the beta3a-adrenoceptor couples only to Gs. To define the regions involved in this differential G protein coupling, we have compared wild-type, truncated, and mutant beta3-adrenoceptors. In Chinese hamster ovary cells expressing beta3-adrenoceptors truncated at the splicing point, cAMP accumulation with CL316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate] increased by 59% following pretreatment with pertussis toxin, suggesting that the C-terminal region of the beta3a-adrenoceptor inhibits coupling to Gi. We next utilized the cell-penetrating peptide Transportan 10 (Tp10) to introduce peptides comprising the different C-terminal tail fragments into cells expressing beta3a-adrenoceptor, beta3b-adrenoceptor, and the truncated beta3-adrenoceptor. Treatment with beta3a-Tp10 (1 microM) caused cAMP responses to CL316243 in the beta3a-adrenoceptor to become pertussis toxin-sensitive and display a 30% increase over control, whereas the other peptides did not affect any receptor. Mutation at a potential tyrosine phosphorylation site (Tyr392Ala beta3a-adrenoceptor) did not alter responses or pertussis toxin sensitivity relative to the parent receptor. Surprisingly, a Ser388Ala/Ser389Ala mutant beta3b-adrenoceptor became unresponsive to CL316243 while retaining an extracellular acidification rate response to SR59230A [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate]. Our findings suggest that the beta3a-adrenoceptor cannot couple to Gi because of conformational changes induced by a protein(s) that interacts with residues in the C-terminal tail or because this protein(s) affects the intracellular localization of the beta3a-adrenoceptor.


Carbamate ester prodrugs of dopaminergic compounds: synthesis, stability, and bioconversion.
Various carbamic acid esters (CAE) of a new class of dopaminergic drugs, 5-substituted 8-chloro-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1 H-3-benzazepines, were synthesized and evaluated as prodrug forms with the aim of protecting the parent phenols against first-pass metabolism following oral administration. Monosubstituted CAE were found to be highly unstable at pH 7.4 and 37 degrees C, the half-lives of hydrolysis being between 4 and 40 min. Plasma from various species catalyzed the hydrolysis of the carbamates. N,N-Disubstituted carbamates, on the other hand, were stable both in buffer and plasma solutions. They showed a very potent inhibition of butyrylcholinesterase (EC 18.104.22.168), but were less potent inhibitors of the specific erythrocyte acetylcholinesterase (EC 188.8.131.52). In vitro incubations of an N,N-dimethylsubstituted carbamate ester (10) with liver microsomes from mouse and rat showed an appreciable formation of the parent phenolic compound. This bioconversion is suggested to occur via an initial cytochrome P-450-catalyzed hydroxylation to give an N-hydroxymethyl derivative which spontaneously decomposes to the N-monomethylcarbamate. It is concluded that N,N-disubstituted carbamate esters may be potentially useful prodrugs for the 7-hydroxy-3-benzazepines, whereas N-monosubstituted carbamates appear to be too chemically and enzymatically labile.


The effect of optimizing EABR parameters in artificial cochlear implantation for auditory rehabilitation.
The objective of the present study was to observe the relationship between V extraction rate and threshold value of electrically evoked auditory brainstem response (EABR) waves in artificial cochlear implantation, in order to optimize EABR parameters for improving auditory rehabilitation. Thirty patients without residual hearing and treated with artificial cochlear implants were selected. The experimental group included 17 cases with normal cochlear morphology, four with large vestibular aqueduct syndrome (LVAS), six with Mondini malformation, and three with internal auditory canal stenosis. Thirty patients with residual hearing and approximate conditions, treated with artificial cochlear implantation to conduct matching were taken as the control group. For artificial cochlear implantation, Remolded Cochlear Freedom artificial cochleas and platinum-iridium alloy spheroid electrodes were used to provide electric stimulation of different pulse widths (50 μs, 100 μs and 200 μs) to patients in the two groups. A Bio-logic Navigator Pro auditory evoked potentiometer was used to record V extraction rate and threshold value of EABR waves under the different pulse widths. There were no significant differences in V extraction rates of EABR waves at pulse widths of 50 μs, 100 μs and 200 μs (p >0.05). All EABR threshold values in the experimental group were higher than those in the control group, and the differences were statistically significant (p <0.05). The monopole stimulation within the cochlea can induce good EABR waves and EABR threshold values of patients without residual hearing were significantly higher than those of patients with residual hearing (p <0.05). Waveform differentiation of pulse width 100 μs was better, dynamic range was broader and it was necessary to increase stimulation when the malformation was serious.


Striated muscle hamartoma of the eyelid in an adult woman.
A 57-year-old woman presented with a recurrent lower eyelid growth that was found to be a striated muscle hamartoma on surgical biopsy. This is a rare entity in adults with no history of congenital abnormality. Several other rare, benign lesions may be clinically similar and should be considered in the differential diagnosis of an eyelid lesion containing striated muscle.


S-adenosylmethionine mediates glutathione efficacy by increasing glutathione S-transferase activity: implications for S-adenosyl methionine as a neuroprotective dietary supplement.
When maintained on a folate-deficient, iron-rich diet, transgenic mice lacking in apolipoprotein E (ApoE-/- mice) demonstrate impaired activity of glutathione S-transferase (GST), resulting in increased oxidative species within brain tissue despite abnormally high levels of glutathione. These mice also exhibit reduced levels of S-adenosyl methionine (SAM) and increased levels of its hydrolysis product S-adenosyl homocysteine, which inhibits SAM usage. Supplementation of the above diet with SAM restored GST activity and eliminated reactive oxygen species at the expense of stockpiled glutathione, suggesting that one or more SAM-dependent reactions were required to maintain GST activity. We examined herein the impact of SAM on GST activity using a cell-free assay. SAM stimulated GST activity in a dose-response manner when added to homogenates derived from the above ApoE-/- mice. SAM also increased activity of purified rat liver GST and recombinant GST. Filtering of SAM through a 4 kDa cutoff and systematic withholding of reaction components eliminated the possibility of any additional contaminating enzyme. These findings confirm that SAM can exert a direct effect on GST activity. Since Alzheimer's disease is accompanied by reduced GST activity, diminished SAM and increased SAH, these findings underscore the critical role of SAM in maintenance of neuronal health.


Novel therapeutic targets for inflammatory bowel disease.
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy. The treat to target approach possibly correlates with minor risk for complications associated with IBD, specially surgery and cancer. The most studied inflammatory pathway in IBD, is described to be dependent of the pro-inflammatory cytokine tumor necrosis factor-alfa (TNF-α), and compose the first line studies for development of biological drugs, in this case, targeting specifically the action of TNF-α. Even though, the use of anti-TNFs drugs are associated with improvement of the inflammation in some patients, a great portion do not respond at first or lose response over time. These findings made clear about the possibility of other mechanisms involved in perpetuating the chronic inflammatory state. Many years of intensive research have led to the identification of different inflammatory pathways that form the basis of the intensive drug development that we are experiencing today. These novel drugs include agents that target leukocyte trafficking, Interleukin (IL) 23, Janus kinases (JAK), Sphingosine 1 phosphate (S1P) and Smad7, an inhibitor of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1). In this manuscript, we aim to review the most promising late-stage drug candidates for the treatment of IBD.


MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics.
Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment.


A reassessment of the echocardiogram in mitral stenosis.
Echocardiographic and cardiac catheterization findings were compared in 61 patients with mitral stenosis without other significant lesions in an attempt to determine the clinical usefulness of echocardiography in the assessment of such patients. There was a poor correlation between the E-F slope on the echocardiogram and the calculated mitral valve area (r = 0.51). A review of reported data relating the E-F slope to mitral valve area indicated that echocardiographic assessment of mitral valve area had low sensitivity and specificity. The amplitude of excursion of the anterior leaflet did not differ significantly in patients undergoing valvotomy and those undergoind valve replacement. The data obtained suggest that while the echocardiogram is a reliable method of diagnosing mitral stenosis, the E-F slope is an unreliable index of the severity of the lesion.


Activation of oncogenes by transposable elements.
Mammalian DNA contains several families of highly repeated sequences, some of which have been suggested to be mobile elements. We have screened tumour tissue for the rearrangement of cellular oncogenes and found evidence for the behaviour of repetitive DNA sequences as transposable elements which may activate oncogenes. In the mouse myeloma NSI and XRPC24 we found that intracisternal A particle genome was inserted into the coding region of c-mos. In both cases the rearranged c-mos was transcriptionally activated and was also able to transform NIH 3T3 cells. In the canine transmissible venereal tumour we found that c-myc was rearranged due to the insertion of an 1.8 kilobase pair cellular DNA. Nucleotide sequence analysis demonstrated that the inserted piece is 60% homologous to the monkey KpnI element which is a representative of the LINE group.


Cancers in Australia in 2010 attributable to overweight and obesity.
To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to overweight/obesity. We estimated the population attributable fraction (PAF) and number of cancers causally associated with overweight/obesity. We used standard formulae incorporating Australian prevalence data for body mass index (BMI), relative risks associated with BMI and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that may have occurred assuming that the prevalence of overweight/obesity had remained at 1990 levels. An estimated 3,917 cancer cases (3.4% of all cancers) diagnosed in 2010 were attributable to overweight/obesity, including 1,101 colon cancers, 971 female post-menopausal breast cancers and 595 endometrial cancers (PAFs of 10%, 8% and 26%, respectively). Highest PAFs were observed for oesophageal adenocarcinoma (31%), endometrial cancer (26%) and kidney cancer (19%). If the prevalence of overweight/obesity in Australia had remained at levels prevailing in 1990, we estimate there would have been 820 fewer cancers diagnosed in 2010 (PIF 2%). Overweight/obesity causes a substantial number of cancers in Australia. Public health strategies to reduce the prevalence of overweight and obesity will reduce the incidence of cancer, particularly of the colon, breast and endometrium.


Identification of 2-Fluoropalmitic Acid as a Potential Therapeutic Agent Against Glioblastoma.
Glioblastomas (GBMs) are aggressive malignant brain tumors. Although chemotherapy with temozolomide (TMZ) can extend patient survival, most patients eventually demonstrate resistance. Therefore, novel therapeutic agents that overcome TMZ chemoresistance are required to improve patient outcomes. Drug screening is an efficient method to find new therapeutic agents from existing drugs. In this study, we explored a novel anti-glioma agent by drug screening and analyzed its function with respect to GBM treatment for future clinical applications. Drug libraries containing 1,301 diverse chemical compounds were screened against two glioma stem cell (GSC) lines for drug candidate selection. The effect of selected agents on GSCs and glioma was estimated through viability, proliferation, sphere formation, and invasion assays. Combination therapy was performed to assess its ability to enhance TMZ cytotoxicity against GBM. To clarify the mechanism of action, we performed methylation-specific polymerase chain reaction, gelatin zymography, and western blot analysis. The acyl-CoA synthetase inhibitor 2-fluoropalmitic acid (2-FPA) was selected as a candidate anti-glioma agent. 2-FPA suppressed the viability and stem-like phenotype of GSCs. It also inhibited proliferation and invasion of glioma cell lines. Combination therapy of 2-FPA with TMZ synergistically enhanced the efficacy of TMZ. 2-FPA suppressed the expression of phosphor-ERK, CD133, and SOX-2; reduced MMP-2 activity; and increased methylation of the MGMT promoter. 2-FPA was identified as a potential therapeutic agent against GBM. To extend these findings, physiological studies are required to examine the efficacy of 2-FPA against GBM in vivo.


Prostatic contribution to normal serum acid phosphatase.
Total and tartrate-labile serum acid phosphatase levels were compared in patients with and without prostates, and in 12 patients before and after cystoprostatectomy. Absence of the prostate seems to make no significant difference to the levels of serum acid phosphatase. There is no justification for referring to the tartrate-labile serum acid phosphatase as "prostatic acid phosphatase." A substantial incidence of marginally raised levels of serum acid phosphatase in each group of patients suggests that the upper limit of normal for the total serum acid phosphatase should be taken as 5 K.A.u.


Introduction to the pharmacology of suprofen.
A number of peripherally acting analgesics have become available in the past two decades for the treatment of mild to moderate pain of diverse etiology. The action of these agents is based on their putative ability to inhibit prostaglandin biosynthesis and attenuate hyperalgesia. Suprofen is a new and potent peripherally acting analgesic with anti-inflammatory and antipyretic properties which appears to inhibit prostaglandin synthetase in a tissue-selective manner. In preclinical studies, suprofen was shown to possess a wide separation of analgesic activity from gastrointestinal irritation. Suprofen appears to exert its pharmacological effect by inhibiting synthesis of prostaglandins from precursor arachidonic acid, inhibiting the pain induced by bradykinin, and by raising the threshold to pain induced by prostaglandins. The onset of action is rapid with peak analgesic effect reached in 1-2 h. Preclinical data suggest that suprofen may be an extremely valuable and versatile analgesic for the clinical management of pain.


High nutrient concentration and temperature alleviated formation of large colonies of Microcystis: Evidence from field investigations and laboratory experiments.
Correlations between Microcystis colony size and environmental factors were investigated in Meiliang Bay and Gonghu Bay of Lake Taihu (China) from 2011 to 2013. Compared with Gonghu Bay, both nutrient concentrations and Microcystis colony sizes were greater in Meiliang Bay. The median colony size (D50: 50% of the total mass of particles smaller than this size) increased from April to August and then decreased until November. In both bays, the average D50 of Microcystis colonies were <100 μm in spring, but colonies within moderate-size (100-500 μm) dominated in summer. The differences in colony size in Meiliang Bay and Gonghu Bay were probably due to horizontal drift driven by the prevailing south wind in summer. Redundancy analysis (RDA) of field data indicated that colony size was negatively related to nutrient concentrations but positively related to air temperature, suggesting that low nutrient concentrations and high air temperature promoted formation of large colonies. To validate the field survey, Microcystis colonies collected from Lake Taihu were cultured at different temperatures (15, 20, 25 and 30 °C) under high and low nutrient concentrations for 9 days. The size of Microcystis colonies significantly decreased when temperature was above 20 °C but had no significant change at 15 °C. The differences in temperature effects on colony formation shown from field and laboratory suggested that the larger colonies in summer were probably due to the longer growth period rather than the higher air temperature and light intensity. In addition, colony size decreased more significantly at high nutrient levels. Therefore, it could be concluded that high nutrient concentration and temperature may alleviate formation of large colonies of Microcystis.


Immunohistochemical study of CD34 and podoplanin in periodontal disease.
The aim of this study was to evaluate the angiogenesis and lymphangiogenesis in gingival tissue biopsy specimens of individuals with clinically healthy gingiva, chronic gingivitis, and chronic periodontitis (n = 30 per clinical condition). Histological sections were stained using hematoxylin and eosin as well as immunohistochemically with hematopoietic progenitor cell antigen CD34 and podoplanin (PDPN) antibodies to evaluate the microvascular count, area, and perimeter of blood and lymphatic vessels, respectively. The results revealed a correlation between the microvascular count of blood and lymphatic vessels (P = 0.03; however, in individuals with chronic periodontitis, fewer lymphatic vessels were present than in the clinically healthy gingival tissue (P = 0.01), which was not observed in the case of microvascular area and perimeter. Podoplanin labeling was present in the epithelium, and the intensity of labeling was positively correlated to the intensity of the inflammatory infiltrate (P = 0.03). In this study, we concluded that an increase in the number of blood and lymphatic vessels was not observed in bouth gingivitis and periodontitis samples. Podoplanin expression is highly associated with an increased inflammatory infiltration suggesting that PDPN might play an additional role in periodontal disease, other than solely as a lymphangiogenesis marker.


Ring-Shaped Phosphinoamido-Magnesium-Hydride Complexes: Syntheses, Structures, Reactivity, and Catalysis.
A series of magnesium(II) complexes bearing the sterically demanding phosphinoamide ligand, L(-) =Ph2 PNDip(-) , Dip=2,6-diisopropylphenyl, including heteroleptic magnesium alkyl and hydride complexes are described. The ligand geometry enforces various novel ring and cluster geometries for the heteroleptic compounds. We have studied the stoichiometric reactivity of [(LMgH)4 ] towards unsaturated substrates, and investigated catalytic hydroborations and hydrosilylations of ketones and pyridines. We found that hydroborations of two ketones with pinacolborane using various Mg precatalysts is very rapid at room temperature with very low catalyst loadings, and ketone hydrosilylation using phenylsilane is rapid at 70 °C. Our studies point to an insertion/σ-bond metathesis catalytic cycle of an in situ formed "MgH2 " active species.


Sec-Dependent Secretion of Subtilase SptE in Haloarchaea Facilitates Its Proper Folding and Heterocatalytic Processing by Halolysin SptA Extracellularly.
In response to high-salt conditions, haloarchaea export most secretory proteins through the Tat pathway in folded states; however, it is unclear why some haloarchaeal proteins are still routed to the Sec pathway. SptE is an extracellular subtilase of Natrinema sp. strain J7-2. Here, we found that SptE precursor comprises a Sec signal peptide, an N-terminal propeptide, a catalytic domain, and a long C-terminal extension (CTE) containing seven domains (C1 to C7). SptE is produced extracellularly as a mature form (M180) in strain J7-2 and a proform (ΔS) in the ΔsptA mutant strain, indicating that halolysin SptA mediates the conversion of the secreted proform into M180. The proper folding of ΔS is more efficient in the presence of NaCl than KCl. ΔS requires SptA for cleavage of the N-terminal propeptide and C-terminal C6 and C7 domains to generate M180, accompanied by the appearance of autoprocessing product M120 lacking C5. At lower salinities or elevated temperatures, M180 and M120 could be autoprocessed into M90, which comprises the catalytic and C1 domains and has a higher activity than M180. When produced in Haloferax volcanii, SptE could be secreted as a properly folded proform, but its variant (TSptE) with a Tat signal peptide does not fold properly and suffers from severe proteolysis extracellularly; meanwhile, TSptE is more inclined to aggregate intracellularly than SptE. Systematic domain deletion analysis reveals that the long CTE is an important determinant for secretion of SptE via the Sec rather than Tat pathway to prevent enzyme aggregation before secretion. IMPORTANCE While Tat-dependent haloarchaeal subtilases (halolysins) have been extensively studied, the information about Sec-dependent subtilases of haloarchaea is limited. Our results demonstrate that proper maturation of Sec-dependent subtilase SptE of Natrinema sp. strain J7-2 depends on the action of halolysin SptA from the same strain, yielding multiple hetero- and autocatalytic mature forms. Moreover, we found that the different extra- and intracellular salt types (NaCl versus KCl) of haloarchaea and the long CTE are extrinsic and intrinsic factors crucial for routing SptE to the Sec rather than Tat pathway. This study provides new clues about the secretion and adaptation mechanisms of Sec substrates in haloarchaea.


A Methionine Sulfoxide Reductase B Is Required for the Establishment of Astragalus sinicus-Mesorhizobium Symbiosis.
Methionine sulfoxide reductase B (MsrB) is involved in oxidative stress or defense responses in plants. However, little is known about its role in legume-rhizobium symbiosis. In this study, an MsrB gene was identified from Astragalus sinicus and its function in symbiosis was characterized. AsMsrB was induced under phosphorus starvation and displayed different expression patterns under symbiotic and nonsymbiotic conditions. Hydrogen peroxide or methyl viologen treatment enhanced the transcript level of AsMsrB in roots and nodules. Subcellular localization showed that AsMsrB was localized in the cytoplasm of onion epidermal cells and co-localized with rhizobia in nodules. Plants with AsMsrB-RNAi hairy roots exhibited significant decreases in nodule number, nodule nitrogenase activity and fresh weight of the aerial part, as well as an abnormal nodule and symbiosome development. Statistical analysis of infection events showed that plants with AsMsrB-RNAi hairy roots had significant decreases in the number of root hair curling events, infection threads and nodule primordia compared with the control. The content of hydrogen peroxide increased in AsMsrB-RNAi roots but decreased in AsMsrB overexpression roots at the early stage of infection. The transcriptome analysis showed synergistic modulations of the expression of genes involved in reactive oxygen species generation and scavenging, defense and pathogenesis and early nodulation. In addition, a candidate protein interacting with AsMsrB was identified and confirmed by bimolecular fluorescence complementation. Taken together, our results indicate that AsMsrB plays an essential role in nodule development and symbiotic nitrogen fixation by affecting the redox homeostasis in roots and nodules.


[Research progress on medicinal resources of Coptis and its isoquinoline alkaloids].
Coptidis Rhizoma is a common Chinese medicinal in clinical practice,with the effects of clearing heat,drying dampness,purging fire,and removing toxin. All the medicinal plants of Coptis can be used for clinical treatment,but some species are endangered due to resource destruction and difficulty in planting. The dominant medicinal components in Coptidis Rhizoma are isoquinoline alkaloids. There are various methods for the analysis and detection of alkaloids,such as LC-MS,HPLC,and TLC,among which LC-MS is the most widely applied. Different plants of Coptis vary in the kind and content of alkaloids. C. chinensis,C. deltoidea,C. teeta,C. chinensis var. brevisepala,C. omeiensis,C. quinquefolia,and C. quinquesecta mainly contain berberine,palmatine,coptisine,jatrorrhizine,and columbamine,five effective alkaloid components. Plant isoquinoline alkaloids( PIAs) have strong pharmacological activity but are difficult to prepare. The application of synthetic biology of PIAs will be helpful for the clinical application of PIAs. This paper reviews the research progress on biological resources of Coptis species and structures of alkaloids as well as analysis methods and synthetic biology for isoquinoline alkaloids in the medicinal plants of Coptis in recent years,which will facilitate the protection of Coptis medicinal resources and the application and development of alkaloids.


Isolation and Characterization of a New Ferulic-Acid-Biotransforming Bacillus megaterium from Maize Alkaline Wastewater (Nejayote).
Nejayote is an alkaline wastewater generated during the nixtamalization process. Nejayote contains high-value compounds such as ferulic acid (FA), which is widely employed as a substrate for the biotechnological production of flavors and aromas. In the present study, the isolation, identification, and characterization of a native strain of Bacillus megaterium were performed, and its capacity to produce 4-vinylguaiacol (4VG) from ferulic acid was evaluated by employing growing cell and resting cell systems. Growing cells of native B. megaterium biotransformed 6 mM crude FA in nejayote into 2.1 mM 4VG, reaching a productivity of 0.21 mM h-1 4VG, while nejayote enriched with FA at 10, 15, and 25 mM resulted in the formation of 2.4, 3.8, and 6.2 mM 4VG and productivities of 0.24, 0.38, and 0.51 mM h-1 4VG, respectively. In the resting cell system, from 6 and 25 mM pure FA, 3.5 mM 4VG was produced (0.18 mM h-1 4VG), while at 10 and 15 mM FA, 4.6 and 5.1 mM 4VG (average of 0.24 mM h-1 4VG) were obtained, respectively. The native B. megaterium strain, isolated from nejayote, showed great biotechnological potential to produce 4VG from crude FA contained in this wastewater, in which other Bacillus species, such as B. licheniformis and B. cereus, were unable to grow and biotransform FA into 4VG.


Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.
A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.


Patterns of brown fat uptake of 18F-fluorodeoxyglucose in positron emission tomography/computed tomography scan.
Fluorodeoxyglucose (FDG) positron emission tomography (PET) has become the common imaging modality in oncological practice. FDG uptake is seen in brown adipose tissue in a significant number of patients. Recognizing the uptake patterns is important for optimal FDG PET interpretation. The introduction of PET/computed tomography (PET/CT) revolutionized PET imaging, bringing much-needed anatomical information. Careful review and correlation of FDG PET images with anatomical imaging should be performed to characterize accurately any lesion having high FDG uptake.


Urinary and biliary excretion of metabolites of halothane in dogs.
To determine the urinary and biliary excretion of metabolites of halothane in dogs, 12 beagles were anesthetized with halothane either at 0.5 MAC (minimum alveolar concentration) for 1 hr or at 1.4 MAC for 4 hr. Urine and bile were then collected for 11 days following the anesthesia. The concentrations of inorganic fluoride in the urine and bile were measured with a fluoride electrode and an ion meter. The concentration of total fluoride containing organic fluoride also was measured in the same manner after conversion of the organic fluoride to an inorganic form by combustion. The concentration of trifluoroacetic acid (TFA) in the urine was measured by ion chromatography and that in the bile by gas chromatography. Over 80% of all the fluoride was excreted in the urine as organic fluoride in both groups. While the fraction of TFA in the organic fluoride in the bile was about 30% in both groups, that in the urine was 40% in the 0.5 MAC group and 65% in the 1.4 MAC group. Therefore, it was concluded that the organic fluoride compounds, the metabolites of halothane, and in particular TFA, were excreted mostly into the urine. The extent of metabolism of halothane decreased from 7.6% in the 0.5 MAC group to 4.9% in the 1.4 MAC group. The urinary excretion rate of TFA, however, was not affected by the concentration of inspired halothane.


The active state of the thin filament is destabilized by an internal deletion in tropomyosin.
The function of three of tropomyosin's sequential quasiequivalent regions was studied by deletion from skeletal muscle alpha-tropomyosin of internal residues 49-167. This deletion mutant tropomyosin spans four instead of the normal seven actins, and most of the tropomyosin region believed to interact with troponin is retained and uninterrupted in the mutant. The mutant tropomyosin was compared with a full-length control molecule that was modified to functionally resemble muscle tropomyosin (Monteiro, P. B., Lataro, R. C., Ferro, J. A., and Reinach, F. C. (1994) J. Biol. Chem. 269, 10461-10466). The tropomyosin deletion suppressed the actin-myosin subfragment 1 MgATPase rate and the in vitro sliding of thin filaments over a heavy meromyosin-coated surface. This inhibition was not reversed by troponin plus Ca2+. Comparable tropomyosin affinities for actin, regardless of the deletion, suggest that the deleted region has little interaction with actin in the absence of other proteins. Similarly, the deletion did not weaken binding of the troponin-tropomyosin complex to actin. Furthermore, Ca2+ had a 2-fold effect on troponin-tropomyosin's affinity for actin, regardless of the deletion. Notably, the deletion greatly weakened tropomyosin binding to myosin subfragment 1-decorated actin, with the full-length tropomyosin having a 100-fold greater affinity. The inhibitory properties resulting from the deletion are attributed to defective stabilization of the myosin-induced active state of the thin filament.


Application of 15N tracing for estimating nitrogen cycle processes in soils of a constructed wetland.
Integrated Constructed Wetlands (ICW) area technology for the attenuation of contaminants such as organic carbon (C), nitrogen (N), phosphorous (P) and sulphur (S) in water coming from point or diffuse sources. Currently there is a lack of knowledge on the rates of gross N transformations in soils of the ICW bed leading to losses of reactive N to the environment. In addition, the kinetics of these processes need to be studied thoroughly for the sustainable use of ICW for removal of excessive N in the treatment of waste waters. Gross N transformation processes were quantified at two soil depths (0-15 and 30-45 cm) in the bed of a surface flow ICW using a 15N tracing approach. The ICW, located in Dunhill village at Waterford in Southeastern Ireland, receives 500 person equivalent waste waters containing large quantities of organic pollutants (ca. mean annual C, N, P and S contents of 240, 60, 5 and 73 mg L-1). Soil was removed from these depths in December 2014 and incubated anaerobically in the laboratory, with either 15N labeled ammonium (NH4+) or nitrate (NO3-), differentially labeled with 14NH415NO3 and 15NH414NO3 in parallel setups, enriched to 50 atm% 15N. Results showed that at both soil depths, NO3- production rates were small, which may have resulted in lower NO3- reduction by either denitrification or dissimilatory NO3- reduction to ammonium (DNRA). However, despite being low, the DNRA rates were greater than denitrification rates. Direct transformation of organic N to NO3-, without mineralization to NH4+, was a prevalent pathway of NO3- production accounting for 28-33% of the total NO3- production. Relative contribution of this process to the total N mineralization was negligible at depth 1 (0.01%) but dominant at depth 2 (99.7%). Total NO3-production to total immobilization of NH4+ and NO3- was very small (<0.50%) suggesting that ICW soils are not a source of NO3-. Despite a large potential of N immobilization existed at both the layers, relative N immobilization to the total N conversion was higher at depth 2 (ca. 2.2) than at depth 1 (ca. 1.5). The NH4+ desorption rate at 30-45 cm was high. However, immobilization in the recalcitrant and labile organic N pools was higher. Mineralization and immobilization of NH4+ processes showed that recalcitrant organic N was the predominant source in ICW soils whereas the labile organic N was comparatively small. Source apportionment of N2O production showed that the majority of the N2O produced through denitrification (ca. 92.5%) followed by heterotrophic nitrification (ca. 5.5%), co-denitrification (ca. 1.90%) and nitrification (0.20%). These results revealed that application of a detailed 15N tracing method can provide insights on the underlying processes of ecosystem based abundances of reactive N. A key finding of this study was that both investigated ICW layers were characterised by large N immobilization which restricts production of NO3- and further gaseous N losses.


New Fe₂O₃-Clay@C Nanocomposite Anodes for Li-Ion Batteries Obtained by Facile Hydrothermal Processes.
New iron-oxide-based anodes are prepared by an environmentally-friendly and low-cost route. The analysis of the composition, structure, and microstructure of the samples reveals the presence of a major hematite phase, which is accompanied by a certain concentration of an oxyhydroxide phase, which can act as a "lithium-reservoir". By using sodium alginate as a binder, the synthesized anodes display superior electrochemical response, i.e., high specific capacity values and high stability, not only versus Li but also versus a high voltage cathode in a full cell. From these bare materials, clay-supported anodes are further obtained using sepiolite and bentonite natural silicates. The electrochemical performance of such composites is improved, especially for the sepiolite-containing one treated at 400 °C. The thermal treatment at this temperature provides the optimal conditions for a synergic nano-architecture to develop between the clay and the hematite nanoparticles. High capacity values of ~2500 mA h g-1 after 30 cycles at 1 A g-1 and retentions close to 92% are obtained. Moreover, after 450 cycles at 2 A g-1 current rate, this composite electrode displays values as high as ~700 mA h g-1. These results are interpreted taking into account the interactions between the iron oxide nanoparticles and the sepiolite surface through hydrogen bonds. The electrochemical performance is not only dependent on the oxidation state and particle morphology, but the composition is revealed as a key feature.


Audiological medicine in the UK: the historical perspective of its role and scope.
A medical, as opposed to a surgical, specialty which was to be entrusted with the investigation, care and management of patients with hearing and balance disorders was established in the UK in 1975. This medical specialty was termed 'audiological medicine' and its specialists, 'audiological physicians'. The relationship of the audiological physician to the ear, nose and throat surgeon is analogous to that between the neurologist and the neurosurgeon, or to that between the cardiologist and the cardiac surgeon. The audiological physician's role needs to be distinguished also from that of the audiologist. An audiologist is a scientist (or technician). (In the UK, science is firmly established as an integral and autonomous discipline within British health-care systems.) The role and scope of the audiological physician is clarified. Audiological physicians are concerned primarily with patients suffering from disorders of auditory communication, equilibrium and spatial disorientation, i.e. 'deaf and dizzy' patients.


An algorithm based on graph theory for the assembly of contigs in physical mapping of DNA.
An algorithm is described for mapping DNA contigs based on an interval graph (IG) representation. In general terms, the input to the algorithm is a set of binary overlapping relations among finite intervals spread along a real line, from which the algorithm generates sets of ordered overlapping fragments spanning that line. The implications of a more general case of the IG, called a probe interval graph (PIG), in which only a subset of cosmids are used as probes, are also discussed. In the specific case of cosmids hybridizing to regions of a YAC, the algorithm takes cross-hybridization information using the cosmids as probes, and orders them along the YAC; if gaps exist due to insufficient coverage of cosmid contigs along the length of the YAC, repetitive use of the algorithm generates sets of ordered overlapping fragments. Both the IG and the PIG can expose problems caused by false overlaps, such as hybridizations due to repetitive elements. The algorithm, has been coded in C; CPU time is essentially linear with respect to the number of cosmids analyzed. Results are presented for the application of a PIG to cosmid contig assembly along a human chromosome 13-specific YAC. An alignment of 67 cosmids spanning a YAC took 0.28 seconds of CPU time on a Convex 220 computer.


Predictive value of speckle tracking technique for coronary artery stenosis in patients with coronary heart disease.
To observe the predictive value of speckle tracking technique (STI) for the degree of coronary artery stenosis in patients with coronary heart disease (CHD). The clinical data of 120 patients with coronary artery stenosis admitted to Affiliated Hospital of Chengde Medical University from Feb. 2022 to Sep. 2022 was analyzed retrospectively. The other 63 patients who sought for medical help because of chest pain underwent Coronary Arteriography (CAG) examination during the same period but with Gensini score > 0 were selected as the control group. Coronary artery stenosis was divided into three subgroups according to the coronary Gensini score: mild, moderate, and severe stenosis. Routine ultrasound and STI techniques were performed in all patients. In addition, left ventricular global radial peak systolic strain (GRS), left ventricular global longitudinal peak systolic strain (GLS), left ventricular global peak systolic strain (GAS) and left ventricular global circumferential peak systolic strain (GCS) were measured and compared between the two groups and among the three subgroups. There were no marked differences identified in conventional ultrasound parameters between the coronary artery stenosis group and control group, but the absolute values of GLS, GRS, GCS, and GAS were lower in the former group compared to control group; and the severe group had the lowest levels of above indexes, followed by moderate group, then mild group and control group (all P < 0.05). The results showed that the area under the curve (AUC) for GLS, GRS, GCS, and GAS in diagnosing coronary artery stenosis were 0.973, 0.933, 0.947, and 0.901, respectively. The AUCs of GLS, GRS, GCS, and GAS for the diagnosis of moderate/severe coronary artery stenosis were 0.968, 0.908, 0.901, and 0.942, respectively, with GAS and GLS assessed with the largest AUC values and higher sensitivity and specificity than other parameters. The global longitudinal strain of left ventricle obtained by STI technique was more sensitive to coronary artery stenosis than that by ultrasound technique, and it had a higher predictive value for coronary artery stenosis.


[Repercussion of mental retardation and associated cerebral palsy on skeletal maturation].
Mental retardation (MR) constitutes a clinical and social relevant condition accounting for 3% of the pediatric population. Studies focusing the repercussion of MR on nutritional status are scarce and, in occasions, have produced contradictory results. To evaluate the nutritional status of mentally retarded children in our Region, on the basis of skeletal maturation. Our sample comprise 128 mentally retarded children (81 boys and 47 girls) aged 0 17 years. In all children a nutritional and social family environment questionnaires and a valuation of a series of nutritional and anthropometric variables were performed. Additionally, bone age was assessed by means of left hand wrist radiograph in a subset of 53 children. A factorial analysis was carried out by means of the statistical package SPSS allowing the obtaining of 2 anthropometric factors and 3 biochemical factors that condensed the most information content. Results of the bone maturation were correlated with age, sex, presence of cerebral palsy (CP), severity of mental retardation, results of nutritional and sociofamilial questionnaire, antiepileptic treatment and nutritional status (anthropometric and biochemical factors). Although a good correlation exists between bone age and chronological age, 50% of mentally retarded children presented delay in their skeletal maturation. The bone maturation was higher in the boys than in the girls. The presence of CP induced an increase of 12% in the delay of the skeletal maturation. The severity of MR induced differences in the bone age. Both quality of diet and score of anthropometric factor I inversely correlated with bone maturation delay. Parent s age and geographical precedence but not antiepileptic therapy affected the bone maturation. Delay in the bone maturation occurs with high prevalence among mentally retarded children. The presence of CP, severity of MR, quality of the diet and sociofamilial and nutritional factors influenced in an outstanding way in the bone maturation.


MiR146a modulates chondrogenesis of bone marrow mesenchymal stem cells by modulating Lsm11 expression.
MicroRNAs play a critical role in bone marrow mesenchymal stem cell (MSC) chondrogenesis and regulate the progression of joint regeneration in osteoarthritis. Our previous research confirmed that miR146a relieves osteoarthritis by modulating cartilage homeostasis. However, few studies have revealed the relationship between miR146a and the chondrogenesis of MSCs, and the exact mechanisms remain unclear. This study aimed to determine the function of miR146a in the chondrogenic differentiation of MSCs and the potential mechanisms involved. MiR146a expression increased during chondrogenesis. MiR146a knockout (KO) led to the increased chondrogenesis of MSCs compared to that in wild-type (WT) MSCs, whereas the overexpression of miR146a by mimics resulted in the decreased chondrogenesis of MSCs, as determined by the mRNA expression of collagen, type II, alpha 1 (COL2A1), aggrecan, cartilage oligomeric matrix protein (COMP), and matrix metallopeptidase 13 (MMP13). Furthermore, cartilage defects could be treated better when injected with spheres induced from miR146aKO MSCs than from WT MSCs, indicating that miR146a inhibits chondrogenesis in vivo. In addition, based on miRNA-mRNA prediction analysis and a dual-luciferase reporter assay, we observed that the deletion of miR146a led to the increased expression of Lsm11 during chondrogenesis and demonstrated that miR146a targeted Lsm11 by binding to its 3'-untranslated region (UTR) and inhibited its translation. The inhibition of Lsm11 by silencing RNA (siRNA) reversed the increased ability of chondrogenesis by knocking out miR146a both in vivo and in vitro, suggesting that miR146a inhibits chondrogenesis by directly inhibiting Lsm11 in MSCs, which may be a novel target for treating osteoarthritis.


Displacement threshold hyperacuity as a predictor of postsurgical visual performance in patients with cataract.
To evaluate the ability of Displacement Threshold Hyperacuity (DTH) in predicting the postoperative visual outcome in patients awaiting cataract surgery and discriminating between the relative performance of the neural and optical components of the visual system. To establish eventually the cut-off DTH values to be used clinically in the preoperative evaluation of patients with cataract. Forty-five subjects admitted for extracapsular cataract extraction with implant were examined preoperatively and postoperatively. In addition to DTH, logMAR visual acuity (VA), contrast sensitivity, and a cataract classification system were used to obtain a more comprehensive assessment of the patient's visual performance. DTH was found to be sensitive to decreased macular function but relatively unaffected by the severity of the cataract; higher thresholds were associated with denser opacities. A preoperative threshold of 50 seconds of arc was found to be the upper limit under which normal macular function is likely. DTH sensitivity and specificity for decreased macular function was 1.00 and 0.8, respectively. If preoperative DTH is 50 seconds of arc or lower, the subject will achieve a postoperative logMAR VA better than 0.3 (Snellen equivalent 20/40). On the contrary, higher DTH seems to give no reliable information about the patient's visual function.


Flutamide-metformin therapy to reduce fat mass in hyperinsulinemic ovarian hyperandrogenism: effects in adolescents and in women on third-generation oral contraception.
Adolescents and young women with menstrual irregularities and hyperinsulinemic hyperandrogenism, so-called polycystic ovary syndrome, have abnormalities in body composition, even when nonobese. The combination of flutamide (125-250 mg/d) and metformin has additive benefits on endocrine- metabolic indices in women with polycystic ovary syndrome. However, it is unknown whether this combination also reverses the abnormalities in body composition in this population, especially if the flutamide dose is further reduced, the combination is given at a young age, and an oral contraceptive (OC) is added. Two randomized 3-month studies with flutamide-metformin were conducted in nonobese patients (n = 45) with hyperinsulinemic ovarian hyperandrogenism. In teenagers [n = 21; approximately 15 yr; no use of OC (OC-)], we determined whether a minidose combination (flutamide 62.5 mg/d) improved body composition and endocrine-metabolic indices, and in young women (n = 24; approximately 18 yr; OC+), we determined whether the addition of the minidose combination to a gestodene-containing OC exerted additive effects on the same variables. In OC- teenagers, flutamide-metformin improved fasting insulin/glucose ratio; serum IGF-binding protein-1, testosterone, SHBG, androstenedione, triglycerides, low- density lipoprotein and high-density lipoprotein cholesterol; lean mass, total fat, and abdominal fat (all P < 0.01). In OC+ women, the addition of flutamide-metformin was associated with gain of lean mass and loss of total fat (P < 0.01 vs. OC alone), but the addition failed to reduce abdominal fat. In conclusion, in nonobese adolescents with hyperinsulinemic ovarian hyperandrogenism, minidose flutamide-metformin reversed endocrine-metabolic anomalies and the excess of fat, including abdominal fat; in women, adding flutamide- metformin to a third-generation OC was also effective in improving body composition, but abdominal adiposity was not improved.


HIV/AIDS prevention in "Indian country": current practice, indigenist etiology models, and postcolonial approaches to change.
Many tribal and urban American Indians and Alaska Native communities have initiated HIV/AIDS prevention and treatment services. The richness, depth, and scope of these efforts, however, are not well known and have not been sufficiently documented in the academic literature. In this article we assess the strengths and weakness of the published literature using the constructs of the socioecological framework. We discuss the need to apply an "indigenist" etiology paradigm to HIV/AIDS risk and protection. Finally, we define and discuss the varied postcolonial approaches to HIV/AIDS prevention, treatment, and healing.


Cloning and functional study of GmRPI2, which is the critical gene of photosynthesis in soybean.
Light provides energy for photosynthesis and is also an important environmental signal that regulates plant growth and development. Ribose-5-phosphate isomerase plays a crucial role in photosynthesis. However, ribose-5-phosphate isomerase has yet to be studied in soybean photosynthesis. To understand the biological function of GmRPI2, in this study, GmRPI2 was cloned, plant overexpression vectors and gene editing vectors were successfully constructed, and transformed into recipient soybean JN74 using the Agrobacterium-mediated method. Using qRT-PCR, we analyzed that GmRPI2 gene expression was highest in leaves, second highest in roots, and lowest in stems. Promoter analysis revealed the presence of multiple cis-acting elements related to light response in the promoter region of GmRPI2. Compared with the control soybean plants, the net photosynthetic rate and transpiration rate of the overexpression lines were higher than those of the control and gene editing lines, while the intercellular CO2 concentration was significantly lower than that of the control and gene editing lines; the total chlorophyll, chlorophyll a, chlorophyll b contents and soluble sugar contents of the overexpression plants were significantly higher than those of the recipient and editing plants, indicating that the GmRPI2 gene can increase The GmRPI2 gene can increase the photosynthetic capacity of soybean plants, providing a theoretical basis and genetic resources for improving soybean yield by regulating photosynthetic efficiency.


[High anion gap metabolic acidosis (pyroglutamic acidosis) induced by chronic acetaminophen use].
Acetaminophen is the most consumable analgesic in the world in the form of medical prescription or self-medication. It is one of the active ingredients most often involved in voluntary poisoning. Lethal dose of acetaminophen classically induces acute hepatic failure on hepatic necrosis. Chronic intake of sub-lethal doses (i.e. near recommended therapeutic doses) of acetaminophen in the presence of certain risk factors may be responsible for another much less recognized pathological manifestation: severe metabolic acidosis with an increased anion gap due to the accumulation of 5-oxoproline or pyroglutamic acid.


A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients.
From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III-IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 micrograms/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5 x 10(9) to 60 x 10(9)/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.


Current Bottlenecks and Challenges of the Microalgal Biorefinery.
Microalgae are increasingly considered as sources of renewable feedstocks for industrial production, and microalgae production now focuses on the multiproduct microalgal biorefinery. However, such a biorefinery presents several bottlenecks that are mainly associated with downstream processes. This reduced downstream efficiency results from unsolved problems related to the culture strategy for the accumulation of different products - the protein versus lipid dilemma - and the dilute nature of the microalgal culture. We identify new trends and propose promising solutions for realizing microalgal biorefineries at industrial scale. New perspectives and challenges are identified in protein properties and in the integration and cooptimization of culture and downstream processes.


Amphicrine differentiation in bronchioloalveolar cell carcinoma.
We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.


[Protective effects of growth hormone en cell cultures of the central nervous system].
We examine a possible protective effect from growth hormone (GH) against radiation in cell cultures of rat embryon brain cortex. Brain cortexes were removed from rat embryos of 17 days development and prepared for cell culture. The culture medium of half the plates was enriched with 500 ng/ml GH. All plates received a radiation dose of 3 Gy per plate and were again incubated for 24 hours. The TUNEL technique was employed to verify cell apoptosis in the irradiated plates and compare its level in plates with and without GH. We observed that irradiated cultures with GH had significantly less cell apoptosis than those without GH and concluded that this hormone excercised a protective effect on the cell cultures. The present study demonstrated the protective effect from GH in rat embryonary cells and suggests the need for future in vitro and in vivo studies using central nervous system cells.


[The influence of sensory deprivation on binocular vision after bilateral cataract extraction with intraocular lens implantation].
Cataract extraction with intraocular lens implantation is one of the most frequent surgical procedures. However, benefits associated with the surgery may be restricted by binocular vision disorders. The purpose of the study is to evaluate binocular function of vision in patients after bilateral cataract extraction in relation to the length of period between surgeries. The study included 50 patients operated twice, due to bilateral cataract. All patients were examined six weeks after the second surgery and divided into three groups according to the operational interval (< 12 months, 12-24 months, > 24 months). Presence of asthenopic symptoms, distance and near squint angle, fusional amplitudes, stereopsis and convergence were evaluated. Asthenopic symptoms were present respectively in 8% (n = 1), 42% (n = 8), 37% (n = 7) of patients in groups 1, 2 and 3. Exophoria was found in 16.6% (n = 2) of cases in the first group, 17.5% (n = 3) in the second group and 31.6% (n = 6) in the third group. There was no significant difference in average prismatic fusional vergence range between groups and a negative correlation between amblyoscopic fusional convergence and the period between surgeries was found. Mean stereopsis was 76.7 +/- 62.1; 89.5 +/- 66,2; 76.8 +/- 66.7 seconds of arc in subsequent groups. Average convergence was: 6.8 < or = 6.9 cm in the first group, 7.1 +/- 3.9 cm in the second group and 7.5 +/- 5.0 cm in the third group. There are significant differences in binocular vision parameters in patients after bilateral cataract extraction in relation to the period between surgeries. The prolongation of this time was connected with increased number of patients complaining to asthenopic symptoms, with exophoria and reduced amblyoscopic fusional convergence.


Apraclonidine and timolol. Combined effects in previously untreated normal subjects.
Twenty healthy subjects were tested for the aqueous-suppressing effects of the alpha 2-adrenergic agonist apraclonidine hydrochloride. Apraclonidine caused a 30% reduction of mean (+/- SD) aqueous flow during the daytime from 2.84 +/- 0.61 microL/min, similar to what has been observed for beta-adrenergic antagonists. Apraclonidine, like acetazolamide and unlike timolol maleate, was able to suppress the aqueous flow of sleeping subjects below the spontaneous nocturnal rate of 1.15 +/- 0.40 microL/min to 0.84 +/- 0.28 microL/min, a 27% change. When apraclonidine and timolol were given together in the daytime, no clinically significant or statistically significant additive effect was observed. The range of flows with either drug alone or the combination of the two measured from 2 to 4 PM was 1.41 to 1.78 microL/min. This result contrasts with studies of the effect of apraclonidine on patients who have received long-term beta-blockers where an additive effect is observed. The lack of an additive effect on flow in previously untreated normal subjects suggests that the two drugs act at least in part via a common pathway.


Risk reduction of diarrhea and respiratory infections following a community health education program - a facility-based case-control study in rural parts of Kenya.
Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities. Cases were defined as patients attending the health facility due to diarrhea or a respiratory infection while controls were patients attending the same health facility for a non-communicable disease defined as an event other than diarrhea, respiratory infection. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the risk of diarrheal or respiratory infection in association with exposure to the health education program. There were 324 cases and 308 controls recruited for the study with 57% of the cases and 59% of the controls being male. Overall, 13% of cases vs. 20% of control patients were exposed to the education program. Participants exposed to the program had 38% lower odds of diarrhea and respiratory infections compared to those not exposed to the program (adjusted OR 0.62, 95% CI 0.41-0.96). A similar risk reduction was observed for participants in the study who resided in areas with water improvement initiatives (adjusted OR 0.65, 95% CI 0.47-0.90). Variables in the adjusted model included water improvement projects in the area and toilet facilities. Findings from this study suggest participants exposed to the education program and those residing in areas with water improvement initiatives have a reduced risk of having diarrhea or respiratory infection.


Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S progression and cellular transformation.
The E2F family of transcription factors is believed to have an essential role in the control of cellular proliferation by regulating the transcription of genes involved in cell cycle progression. Previous work has demonstrated that the targeted inactivation of E2f1, E2f2, and E2f3 results in elevated p21(CIP1) protein levels, loss of E2F target gene expression, and cell cycle arrest at G1/S and G2/M, suggesting a strict requirement for these E2Fs in the control of normal cellular proliferation. We now demonstrate that E2f1, E2f2, and E2f3 are also required for oncogene-mediated transformation of mouse embryonic fibroblasts. Analysis of synchronized populations of mouse embryonic fibroblasts revealed that the inactivation of p21(CIP1) restores the ability of E2f1-3-deficient cells to enter and transit through G1/S (but not G2/M). In contrast, loss of p53 restored the ability of these cells to progress through both G1/S and mitosis, leading to their continued proliferation. The inactivation of p53 (but not p21(CIP1)) rendered E2f1-3-deficient cells sensitive to transformation and tumorigenesis. These results suggest that the negative regulation of the p53-p21(CIP1) axis by the E2F1-3 factors is critical for cell cycle progression and cellular transformation.


Archaeal Flagella as Biotemplates for Nanomaterials with New Properties.
At the end of 1980s, regions of the polypeptide chain of bacterial flagella subunits (flagellins) responsible for different properties of these protein polymers were identified by structural studies. It was found that the N- and C-terminal regions are responsible for the polymerization properties of subunits, and the central region is responsible for antigenic properties of the flagellum. Soon after that, it was proposed to use variability of the central flagellin domain for directed modification to impart new properties to the flagellum surface. Such studies of flagella and other polymeric structures of bacterial origin thrived. However bacterial polymers have some shortcomings, mainly their instability to dissociating effects. This shortcoming is absent in archaeal flagella. A limiting factor was the lack of the three-dimensional structure of archaeal flagellins. A method was developed that allowed modifying flagella of the halophilic archaeon Halobacterium salinarum in a peptide that connects positively charged ions. Later, corresponding procedures were used that allowed preparing the anode material for a lithium-ion battery whose characteristics 4-5-fold exceeded those of batteries commonly used in industrial production. We describe other advantages of archaeal flagella over bacterial analogs when used in nanotechnology.


The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion.
The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.


Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics.
In the past decade, nanotechnology has advanced rapidly, and many products containing nanoparticles are now an important part of our daily lives. Despite our increasing exposure to nanoparticles, however, information regarding the absorption, distribution, metabolism, excretion, and toxicity of nanoparticles remains limited. In this review, we introduce our group's ongoing research into the biological effects and toxicities of nanoparticles, which we broadly refer to as "nano-safety research." In addition to determining the biological effects of nanoparticles and elucidating the underlying mechanisms of those effects, we are also exploring the associations among the physicochemical properties and kinetics of nanoparticles. Furthermore, we are currently developing a battery of biomarkers that we hope will be used to predict the biological effects of nanoparticles during the early stages of development. Our research provides valuable basic information on the safety of nanoparticles. We hope that this information will be used for the development of better assessments of nanoparticles safety and for the creation of more appropriate regulations to ensure not only the safety but also the sustainability of nanotechnology.


Outcome of inferior vena cava and noncaval venous leiomyosarcomas.
Leiomyosarcoma (LMS) is a rare tumor arising from the smooth muscle cells of arteries and veins. LMS may affect both the inferior vena cava (IVC) and non-IVC veins. Because of its rarity, the experience with the outcome of the disease originating from the IVC compared with that with non-IVC offspring is overall limited. In this study, we compared the clinical features and outcomes after operative resection of IVC and non-IVC LMS to detect possible significant differences that could affect treatment and prognosis. Twenty-seven patients undergoing operative resection of a venous LMS at a single tertiary care center and one secondary care hospital were reviewed retrospectively and divided into 2 groups: IVC-LMS (Group A, n = 18) and non-IVC LMS (Group B, n = 9). As primary end points, postoperative mortality and morbidity, disease-specific survival and, if applicable, patency of venous reconstruction were considered. Bivariate differences were compared with the χ(2) test. Disease-specific survival was expressed by a life-table analysis and compared using the log-rank test. No postoperative mortality was observed in either group. Postoperative morbidity was 28% in group A and 11% in group B (P = .33). The mean duration of follow-up was 60 months (range, 13-140). Disease-specific survival was 60% in group A and 75% in group B at 3 years (P = .48), and it was 54% in group A and 62% in group B at 5 years (P = .63). Seven grafts were occluded in group A (39%) and 1of 3 were occluded in group B (33%) (P = .85). IVC and non-IVC LMS exhibit similar outcomes in terms of postoperative course and survival. Operative resection associated with vascular reconstruction, if applicable, eventually followed by radiation and chemotherapy may be curative and is associated with good functional results.


Comparison of the efficacy of standard bariatric surgical procedures on Saudi population using the bariatric analysis and reporting outcome system.
To compare the efficacy of various standard bariatric surgical procedures using the Bariatric Analysis and Reporting Outcome System (BAROS). Methods: This is a prospective, descriptive analytical study conducted in 2 medical institutions in Saudi Arabia. A total of 270 patients who had different bariatric surgery during the period between March 2010 and December 2012 were included. The data was analyzed and scored against 3 outcomes, excess weight loss, cure or improvement of comorbidities, and quality of life changes. Results: All patients who had different bariatric procedures were included in our study. Seventy-nine (29.3%) underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP), 159 (58.9%) had laparoscopic sleeve gastrectomy (LSG), and 32 (11.9%) had laparoscopic adjustable gastric banding (LAGB). Complete remission of at least one comorbidity was reported in 36% of LRYGBP, 51% in LSG, and 42% in LAGB. While all other patients have improved comorbidities. The BAROS score was good or higher in 78.5% of LRYGBP, 83.6% for the LSG, and 84.4% of LAGB patients. The average excess weight loss was 67.9% in LRYGBP, 75.8% in LSG, and 81.7% LAGB patients. Conclusion: Bariatric surgery provides a substantial reduction in excess weight, improvement and cure of comorbidities, and improvement in quality of life. Standard bariatric procedures have different degrees of outcomes that can be beneficial in selecting appropriate procedure for appropriate indications and patients.


Hedychium coronarium extract arrests cell cycle progression, induces apoptosis, and impairs migration and invasion in HeLa cervical cancer cells.
Hedychium coronarium Koen. (Zingiberaceae) is traditionally used as medicine in countries such as India, China, and Vietnam for treatment of various ailments including cancer. However, in spite of its implied significance in cancer treatment regimes, there are no reports so far involving the anticancerous attributes of H, coronarium ethanol extract (HCEE) on cancer cells and a more comprehensive study on its mechanism is still lacking. The cytotoxicity of HCEE was evaluated by MTT and clonogenic survival assay. Annexin V/propidium iodide (PI), Hoechst 33342 staining, and TUNEL assay were performed to detect apoptosis. Cell cycle analysis was performed using PI staining. JC-1 and 2',7'-dichlorodihydrofluorescein diacetate assay were used to check the levels of MMP and ROS, respectively. Western blot analysis was carried out to measure the expression levels of proteins. Migration and invasion activity were assessed by wound healing and Transwell membrane assay, respectively. Antiproliferative effect of HCEE was investigated in various cancerous and normal cell lines. Among these, HCEE significantly inhibited the survival of HeLa cells without affecting the viability of normal human umbilical vein endothelial cells. Annexin V/PI, Hoechst staining, and TUNEL assay showed HCEE induced apoptosis in HeLa cells in a dose-dependent manner. HCEE promoted cell cycle arrest at G1 phase in HeLa cells by upregulating the levels of p53 and p21 and downregulating the levels of cyclin D1, CDK-4, and CDK-6. Moreover, HCEE treatment upregulated the expression of Bax and downregulated the expression of Bcl-2. Additionally, HCEE activated the caspase cascade by increasing the activities of caspase-9, caspase-8, and caspase-3. The expression levels of Fas ligand and Fas were also upregulated. Further, HCEE inhibited the migratory potential of HeLa cells by downregulating MMP-2 and MMP-9 expression levels. Our results indicate H. coronarium exerts antiproliferative and apoptotic effects against HeLa cells, and therefore may be used for treatment against cervical cancer.


An Electronic Patient-Reported Outcome Tool for the FACT-B (Functional Assessment of Cancer Therapy-Breast) Questionnaire for Measuring the Health-Related Quality of Life in Patients With Breast Cancer: Reliability Study.
The most frequent malignant disease in women is breast cancer. In the metastatic setting, quality of life is the primary therapeutic goal, and systematic treatment has only a limited effect on survival rates; therefore, the concept of the health-related quality of life (HRQoL) and measurement of patient-reported outcomes (PROs) are gaining more and more importance in the therapy setting of diseases such as breast cancer. One of the frequently used questionnaires for measuring the HRQoL in patients with breast cancer is the Functional Assessment of Cancer Therapy-Breast (FACT-B). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. ePRO tools for the FACT-B questionnaire with proven reliability are missing so far. The aim of this study was to analyze the reliability of tablet-based measurement of FACT-B in the German language in adjuvant (curative) and metastatic breast cancer patients. Paper- and tablet-based questionnaires were completed by a total of 106 female adjuvant and metastatic breast cancer patients. All patients were required to complete the electronically based (ePRO) and paper-based version of the FACT-B. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability using Wilcoxon test and test of internal consistency using Spearman ρ) and agreement rates for single items, Kendall tau for each subscale, and total score were analyzed. High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patients' response behavior between paper-based and electronically based questionnaires. Regarding the reliability test of parallel forms, no significant differences were found in 35 of 37 single items, while significant correlations in the test for consistency were found in all 37 single items, in all 5 sum individual item subscale scores, as well as in total FACT-B score. The ePRO version of the FACT-B questionnaire is reliable for patients with breast cancer in both adjuvant and metastatic settings, showing highly significant correlations with the paper-based version in almost all questions all subscales and the total score.