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pubmed_227_7123
BACKGROUND Perianal dermatitis is probably the most common cutaneous disorder of the genitoanal area. Studies on the epidemiology of causative factors are rare. METHODS Over a 4-year period we prospectively studied 126 patients with a presumptive diagnosis of anal eczema. The diagnostic algorithm comprised medical history, inspection, microbiology, laboratory chemistry, patch tests, proctoscopy, and biopsy if appropriate. RESULTS The age range was 7-82 years and the majority of patients were male (57.1%). Periods of anal symptomatology ranged from 6 days to 120 months and most of the patients (51.6%) had complaints for more than 12 months. The clinical diagnosis in 68 patients (54%) was: intertrigo/candidiasis (42.9%), atopic dermatitis (6.3%), pruritus ani (5.6%), psoriasis (3.2%), skin atrophy from steroid use (2.4%), lichen sclerosus et atrophicus (n = 2), herpes simplex (n = 1), and condylomata acuminata (n = 1). Contact eczema was suspected in 58 patients (46%), but 25 of these (43.1%) showed no contact sensitization. CONCLUSION The majority of patients with symptoms of anal eczema suffer from intertrigo/candidiasis, and relevant, causative contact sensitization may be found in only some of them. Patch-testing is a valuable investigative tool only when the patients' own products are included in the test series. Most patients suffer from their perianal complaints for more than 12 months, therefore diligent evaluation is warranted.
10.1007/s00508-006-0529-x
pubmed_835_24335
OBJECTIVES Dental graduates must graduate with high levels of clinical skills. Education in the clinical environment needs to be more than didactic supervision of practice by clinical teachers. Appropriate feedback in this context, is therefore critical to the development of student competence and confidence. This study was conducted to enhance and develop the assessment and feedback processes during clinical sessions in a Dental University Hospital in an effort to contribute to the development of students' self-assessment skills, reflective ability and clinical competence. METHODS A new evidence-based model of feedback was introduced between clinical teachers and dental students. The implementation of this model was evaluated by students through a survey and focus groups. Descriptive and inferential statistics were applied to the quantitative data, while thematic analysis applied to the qualitative data. RESULTS Findings from the survey indicated that students perceived the new model of feedback to be a positive addition to their learning experiences. The majority indicated a preference to continue using it. Quantitative analysis also demonstrated that students placed a high value on the feedback they received through the new model and associated it with improved individual performance. Five themes generated from the qualitative analysis echoed the perception that the model of feedback enhanced learning opportunities, especially when it was focused on individual performance and incorporated peer feedback. Students' preferences in relation to feedback processes were also gleamed from quantitative and qualitative analyses, that is, provision of positive and constructive feedback, both in dialogue and in written formats, delivered during and after each clinical session and addressing their individual competency learning goals for the future. Some challenges to be addressed were also identified (e.g., time constraints, inter-personal issues, and non-conducive environments). CONCLUSIONS Feedback is central to learning and remains a complex and challenging area. By adopting effective and evidence-based feedback practices through the introduction of a feedback model, students can be supported in regulating their own learning in the clinical learning environment.
10.1186/s12909-022-03630-1
pubmed_922_162
The aim of this study was to determine the prognostic value of circulating angiogenic cytokines in non-metastatic colorectal cancer (CRC) patients. Preoperative serum samples of a training (TC) (n = 219) and a validation cohort (VC) (n = 168) were analyzed via ELISA to determine PlGF, EGF, VEGF, Ang1, PDGF-A, PDGF-B, IL-8 and bFGF levels. In addition, survival was correlated with PlGF and EGF expression measured by microarray and RNAseq in two publicly available, independent cohorts (n = 550 and n = 463, respectively). Prognostic values for overall (OS) and disease-free survival (DFS) were determined using uni- and multivariate Cox proportional hazard analyses. Elevated PlGF is predictive for impaired OS (TC: HR 1.056; p = 0.046; VC: HR 1.093; p = 0.001) and DFS (TC: HR 1.052; p = 0.029; VC: HR 1.091; p = 0.009). Conversely, elevated EGF is associated with favorable DFS (TC: HR 0.998; p = 0.045; VC: HR 0.998; p = 0.018) but not OS (TC: p = 0.201; VC: p = 0.453). None of the other angiogenic cytokines correlated with prognosis. The prognostic value of PlGF (OS + DFS) and EGF (DFS) was confirmed in both independent retrospective cohorts. Serum PlGF and EGF may serve as prognostic markers in non-metastatic CRC.
10.1038/s41598-019-47429-5
pubmed_1055_17339
Compared with lymphoid tissues, the immune cell compartment at mucosal sites is enriched with T cells bearing the γδ T-cell receptor (TCR). The female reproductive tract, along with the placenta and uterine decidua during pregnancy, are populated by γδ T cells predominantly expressing the invariant Vγ6(+)Vδ1(+) receptor. Surprisingly little is understood about the function of these cells. We found that the majority of γδ T cells in the non-pregnant uterus, pregnant uterus, decidua and placenta of mice express the transcription factor RORγt and produce interleukin-17 (IL-17). In contrast, IFNγ-producing γδ T cells were markedly reduced in gestational tissues compared with uterine-draining lymph nodes and spleen. Both uterine-resident invariant Vγ6(+) and Vγ4(+) γδ T cells which are more typically found in lymphoid tissues and circulating blood, were found to express IL-17. Vγ4(+) γδ T cells were particularly enriched in the placenta, suggesting a pregnancy-specific recruitment or expansion of these cells. A small increase in IL-17-producing γδ T cells was observed in allogeneic compared with syngeneic pregnancy, suggesting a contribution to regulating the maternal response to paternally-derived alloantigens. However, their high proportions also in non-pregnant uteri and gestational tissues of syngeneic pregnancy imply a role in the prevention of intrauterine infection or quality control of fetal development. These data suggest the need for a more rigorous evaluation of the role of IL-17 in sustaining normal pregnancy, particularly as emerging data points to a pathogenic role for IL-17 in pre-eclampsia, pre-term birth, miscarriage and maternal immune activation-induced behavioral abnormalities in offspring.
10.1038/icb.2016.48
pubmed_43_5705
Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case-control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a "risk distance" to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10-12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants.
10.1038/s41398-021-01496-3
pubmed_571_20765
In patients with multiple hepatocellular carcinomas (HCCs), a liver resection for the main tumor may be performed in combination with local ablation therapy for satellite lesions. Of 63 multiple HCC patients without radiological vascular invasions, 27 were treated with liver resection alone and the other 36 treated with the combination of liver resection and local ablation therapy. No significant differences were found in both groups with regard to age, gender, BMI, etiology of hepatitis, liver damage grade, tumor number, size of the main tumor and size of satellite lesion. In the liver resection group, 11 hemihepatectomies, 12 sectionectomies and 4 partial hepatectomies were performed. In the combination therapy group, 8 hemihepatecomies, 17 sectionectomies and 11 partial hepatectomies were performed. No significant differences were found in both groups with respect to bleeding, transfusion, disease-free survival rate, and survival rate. In the combination therapy group, a resected liver volume was significantly lower (p = 0.003) and an operation time was shorter (p = 0.009). It appears to indicate that the combination of liver resection and local ablation therapy can be useful for multiple HCCs.
pubmed_571_20765
pubmed_746_5920
Potassium is an essential element for plant, and high-affinity K+ uptake system plays a crucial role in potassium absorption and transportation. Here we report the isolation and characterization of a HKT1 homolog from C3 halophyte Suaeda salsa (L.) (SsHKT1), particularly under low K+ treatment. The SsHKT1 cDNA was 2033 nucleotides long including 1650 bp ORF for a 550 amino acids peptide and a predicted molecular mass of 63.0 kDa. The deduced amino acid sequence of SsHKT1 was 39-64% identical to other plant HKT-like sequences. A SsHKT1-specific antibody was prepared and reacted with a 63.0 kDa protein from S. salsa plasma membrane. Reverse transcriptase-PCR analysis showed that SsHKT1 was mainly expressed in leaf tissues and to a lesser extent, in root tissues. Amounts of SsHKT1 transcript were developmentally controlled and significantly up-regulated by K+ deprivation and NaCl treatment. The results suggested that SsHKT1 might play an important role in ion homeostasis and salt tolerance of S. salsa.
10.1080/10425170701447465
pubmed_273_10089
Glycoside hydrolase family 1 (GH1) beta-glucosidases play roles in many processes in plants, such as chemical defense, alkaloid metabolism, hydrolysis of cell wall-derived oligosaccharides, phytohormone regulation, and lignification. However, the functions of most of the 34 GH1 gene products in rice (Oryza sativa) are unknown. Os3BGlu6, a rice beta-glucosidase representing a previously uncharacterized phylogenetic cluster of GH1, was produced in recombinant Escherichia coli. Os3BGlu6 hydrolyzed p-nitrophenyl (pNP)-beta-d-fucoside (k(cat)/K(m) = 67 mm(-1) s(-1)), pNP-beta-d-glucoside (k(cat)/K(m) = 6.2 mm(-1) s(-1)), and pNP-beta-d-galactoside (k(cat)/K(m) = 1.6 mm(-1)s(-1)) efficiently but had little activity toward other pNP glycosides. It also had high activity toward n-octyl-beta-d-glucoside and beta-(1-->3)- and beta-(1-->2)-linked disaccharides and was able to hydrolyze apigenin beta-glucoside and several other natural glycosides. Crystal structures of Os3BGlu6 and its complexes with a covalent intermediate, 2-deoxy-2-fluoroglucoside, and a nonhydrolyzable substrate analog, n-octyl-beta-d-thioglucopyranoside, were solved at 1.83, 1.81, and 1.80 A resolution, respectively. The position of the covalently trapped 2-F-glucosyl residue in the enzyme was similar to that in a 2-F-glucosyl intermediate complex of Os3BGlu7 (rice BGlu1). The side chain of methionine-251 in the mouth of the active site appeared to block the binding of extended beta-(1-->4)-linked oligosaccharides and interact with the hydrophobic aglycone of n-octyl-beta-d-thioglucopyranoside. This correlates with the preference of Os3BGlu6 for short oligosaccharides and hydrophobic glycosides.
10.1104/pp.109.139436
pubmed_1124_1407
OBJECTIVE To determine the sensitivity and specificity of radiographic evaluation of radio-ulnar incongruence in canine elbow joints in vitro. STUDY DESIGN Radiographic evaluation of induced radio-ulnar incongruence in canine cadaveric forelimbs by radiologists blinded to study design. SAMPLE POPULATION Six cadaveric canine left forelimbs. METHODS Extended lateral, 90 degrees flexed lateral, and cranio-caudal projections were taken of the elbow joint of six cadaveric canine forelimbs. A four-pin, type I external skeletal fixator (ESF) with a linear motor side bar was attached to the medial aspect of the radius, and a 2-cm segment of bone was removed from the mid-diaphysis. A 3.5-mm cortical bone screw placed from the medial to lateral styloid processes prevented relative movement between the distal radius and ulna during radial shortening. The ESF was used to progressively shorten the radius in increments of 0.5 mm to a total of 4 mm. The three radiographic projections were repeated after each incremental change of length. After the study, each elbow joint was disarticulated to confirm the presence of a step defect. The original radiographs and three copies were randomized and then evaluated by four radiologists blinded to the study design. Radiologists were asked to evaluate whether the joint was normal or abnormal and if there was evidence of radio-ulnar incongruence. The ability of each radiologist to correctly identify congruent elbows (specificity) and incongruent elbows (sensitivity) was calculated. RESULTS The median specificity was 86% using the lateral projection and 82% using the cranio-caudal projection. The median sensitivities using the lateral and cranio-caudal radiographic projections were 78% and 79%, respectively. The degree of radial shortening required for individual radiologists to achieve a sensitivity of 90% ranged from 1.5 mm to greater than 4 mm. CLINICAL RELEVANCE Standard radiographic evaluation for radio-ulnar incongruence in the dog may be associated with relatively poor sensitivity and specificity. Invasive surgical procedures and screening programs that rely on radiographic diagnosis of radio-ulnar incongruence should be discouraged until a more reliable method of diagnosis of this type of elbow joint incongruence is available.
10.1053/jvet.2002.31046
pubmed_1037_18670
Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure.This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.
10.1016/j.arbres.2020.03.005
pubmed_972_13871
UNLABELLED We previously showed evidence for a genetic association of the human leukocyte antigen (HLA) system and complex regional pain syndrome (CRPS) with dystonia. Involvement of the HLA system suggests that CRPS has a genetic component with perturbed regulation of inflammation and neuroplasticity as possible disease mechanisms. However, it is at present unclear whether the observed association with HLA-B62 and HLA-DQ8 in CRPS patients with dystonia also holds true for patients without dystonia. Therefore, we tested the possible association with HLA-B62 and HLA-DQ8 in a clinically homogeneous group of 131 CRPS patients without dystonia. In addition, we investigated the possible association with other alleles of the HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci. We showed an increased prevalence of HLA-DQ8 (molecularly typed as HLA-DQB1*03:02; OR = 1.65 [95% CI 1.12-2.42], P = .014) in CRPS without dystonia, whereas no association was observed for HLA-B62 (molecularly typed as HLA-B*15:01; OR = 1.22 [95% CI .78-1.92], P = .458). Our data suggest that CRPS with and CRPS without dystonia may be genetically different, but overlapping, disease entities because only HLA-DQ8 is associated with both. The findings also indicate that distinct biological pathways may play a role in both CRPS subtypes. PERSPECTIVE This study is the first to replicate a specific HLA region conferring genetic risk for the development of CRPS. Moreover, associations of HLA-DQ8 with both CRPS with and CRPS without dystonia, and HLA-B62 only with CRPS with dystonia, suggest that these disease entities may be genetically different, but overlapping.
10.1016/j.jpain.2012.05.003
pubmed_396_3948
Cultured human luteinized granulosa cells (GC) are a unique model to study regulation of the human corpus luteum, e.g. by local factors, including acetylcholine (ACh). GC express functional ACh-receptors of the M1-type (M1R). Priming with the cholinergic agonist carbachol for 24 h, followed by a 24 h stimulation with human chorionic gonadotrophin (hCG), significantly increased progesterone levels (up to 2-fold), compared with hCG stimulation alone. This is likely due to the effect of carbachol, observed after 24 h, to increase the levels of steroid acute regulatory (StAR) protein, as found in Western blots. StAR protein was increased (2-10-fold), while P450 side chain cleavage (SCC) enzyme was unaffected. Thus, one role of muscarinic receptor activation in human GC is regulation of StAR protein and, subsequently, progesterone production.
10.1016/s0303-7207(00)00420-2
pubmed_935_3641
An acidic cholesteryl ester hydrolase (EC 3.1.1.13) from rat liver lysosomes was purified approximately 120-fold with 5% recovery of the original homogenate activity. The sequential steps were: digitonin solubilization, agarose gel filtration, DEAE-agarose and CM-agarose column chromatography. The enzyme was at least 90% pure as judged by polyacrylamide gel electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis. It exhibited a molecular weight of about 60 000 as determined by sodium dodecyl sulfate polyacrylamide electrophoresis and gel filtration. The soluble enzyme required substrate which was incorporated into phospholipid vehicles for optimal activity. On the contrary, aggregates of the enzyme required a substrate preparation that involved the direct addition of cholesteryl ester in acetone. The enzyme also catalyzed the hydrolysis of emulsions of triacylglycerol. The ratio of the two activities remained almost constant during purification suggesting that the two activities (EC 3.1.1.13 and EC 3.1.1.3, respectively) may be the result of the broad specificity of one enzyme. The effects of some inhibitors and some properties of the enzyme have been studied and discussed.
10.1016/0005-2760(80)90173-3
pubmed_89_23892
BACKGROUND/AIMS There is a close link between iron and polyamine biosynthesis and metabolism. In a recent study, we reported alterations in the serum levels of hepcidin and other iron-related proteins in Alzheimer's disease (AD) patients (Sternberg et al., 2017). Based on these findings, this pilot study compared serum levels of one of the polyamines, Spermidine, between AD, mild cognitive impairment (MCI), and control subjects, correlating the levels with the existing clinical and neuroimaging data. METHODS This cross-sectional study measured Spermidine levels in frozen serum samples of 43 AD patients, 12 MCI patients, and 21 age-matched controls, provided by the Oregon Alzheimer's Disease Center Bio-repository, using enzyme-linked immunosorbent assay. RESULTS MCI patients showed significantly higher mean Spermidine serum levels compared to controls (P = 0.01), with a non-significant trend for higher Spermidine serum levels in pure AD (P = 0.08) participants compared to controls. Spermidine serum levels correlated with the values of cognitive assessment tests including MMSE (r = -0.705, P = 0.003), CDR (r = 0.751, P = 0.002), and CDR-SOB (r = 0.704, P = 0.007), in "pure" AD subgroup, suggesting that higher Spermidine serum levels in MCI can be a potential biomarker of conversion to dementia in subjects with AD underlying pathology. Furthermore, Spermidine serum levels correlated with serum levels of the chief iron regulatory protein, hepcidin in AD participants with a more advanced disease stage, indicated by MMSE (strata of 8-19, P = 0.02), and CDR-SOB (strata of 6-12, P = 0.03). CONCLUSION Studies with larger cohort are warranted for defining the role of Spermidine in AD pathophysiology, and the utility of polyamines as biomarkers of progression of MCI to AD.
10.1016/j.jocn.2022.04.028
pubmed_239_8231
Solid-phase extraction (SPE) based on reusable magnetic chitosan microspheres was coupled with ICP-MS for separation and quantification of silver nanoparticles (AgNPs) in the presence of silver ions in environmental water samples. The monodisperse magnetic chitosan microspheres with an average size of 2µm were engineered using suspension cross-linking technique, and characterized and investigated for its application as SPE adsorbent. Parameters affecting the SPE were optimized, and the best performance was achieved by extracting a 20mL sample (pH 4.5) with 10mg adsorbent for 90min, followed by elution with 1mL 1% (w/v) thiourea in 10% (v/v) nitric acid for 10min. The detection limit, calculated as 3s (s, standard deviation for 11 blank readings), for three AgNPs coated with polyvinyl pyrrolidone (PVP), citrate and polyvinyl alcohol (PVA) and sizes of 31, 40, 46nm, respectively, were in the range of 0.016‒0.023μg/L. The repeatability and reproducibility (RSD, n=7) at a spiking level of 0.1μg/L AgNPs were 4.2% and 8.1%, respectively. The developed method has been applied in the analysis of AgNPs in river, lake and wastewater samples, with excellent extraction efficiencies (84.9‒98.8%) for AgNPs at spiking levels of 0.86 and 8.70μg/L. The cationic chitosan microspheres showed good species selectivity and reusability for extraction of AgNPs in the presence of Ag+, and hence the proposed method is simple, cost effective and environmentally friendly.
10.1016/j.talanta.2017.03.064
pubmed_540_4930
Primary health care providers are often confronted with patients describing adverse reactions to food. With a multiplex of differential diagnoses, it is essential to have a structured approach to these complaints. Just as allergies can have a negative impact on quality of life, inappropriate food allergy labelling can cause unnecessary distress and hardship for patients. Understanding the diagnostic approaches to adverse food reactions, alongside an appreciation of multidisciplinary collaboration, can assist the clinician in making appropriate decisions in the management of these patients.
10.4102/safp.v64i1.5530
pubmed_439_11649
Lead-free metal halide light-emitting diodes (LEDs) based on cesium copper halide (CsCu2I3) self-trapped-exciton (STE) emissions show great potential in lighting and color display applications, especially because of their nontoxicity and earth abundance. However, so far, the efficiency and color purity of CsCu2I3-based LEDs remain low. Here we demonstrate the emission of a CsCu2I3 emitter can be enhanced and narrowed in a top-emitting microcavity device. Consequently, the CsCu2I3-based LED device with the assistance of a top-emitting microcavity has significantly narrowed and enhanced the emission spectrum with a full width at half-maximum of 59 nm and a maximum forward brightness of 14767 cd m-2. To the best of our knowledge, this work achieves the narrowest CsCu2I3 LED spectra and demonstrates the potential of employing the microcavity effect to increase the efficiency and color purity of STE-based light-emitting devices.
10.1021/acs.jpclett.2c00740
pubmed_914_16515
BACKGROUND The aim of this study is to explore the association between celiac disease and menstrual cycle, gestation and puerperal disorders. METHODS The association between celiac disease and menstrual cycle, gestation and puerperal disorders in a sample of 62 childbearing age women (15-49 age) was assessed within an age and town of residence matched case-control study conducted in 2008. Main outcome measures were the presence of one or more disorders in menstrual cycle and the presence of one or more complication during pregnancy. RESULTS 62 celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle disorders has been observed in celiac women. 19.4% frequency of amenorrhea was reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI = 7.17-151.8;, p = 0.000). An association has been observed between celiac disease and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The likelihood of having at least one complication during pregnancy has been estimated to be at least four times higher in celiac women than in healthy women (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for celiac disease and threatened abortion, gestational hypertension, placenta abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction (p < 0.001). A shorter gestation has on average been observed in celiac women together with a lower birth weight of celiac women babies (p < 0.001). CONCLUSIONS The occurrence of a significant correlation between celiac disease and reproductive disorders could suggest to consider celiac disease diagnostic procedures (serological screening) in women affected by these disorders.
10.1186/1471-230X-10-89
pubmed_311_19803
The Tityus stigmurus scorpion is widely distributed in the Northeast of Brazil and is the main causal agent of human envenoming. The venom produced by this scorpion includes neurotoxins, which are peptides belonging to Family 2 toxins and are able to interact with ion channels. The KTx subfamily displays selectivity and affinity for Kv channel subtypes and the result of this interaction is the blockade of potassium channels, impairing vital functions. We report the optimized structural model of a transcript encoding a potassium channel blocker toxin from T. stigmurus. LC-MS analysis confirmed the presence of the toxin in the venom and the three-dimensional structure was obtained by computational homology modeling and refined by molecular dynamic simulations. Furthermore, docking simulations were performed using a Shaker kV-1.2 potassium channel from rats as receptor model and the contacts were identified revealing which amino acid residues and interactions could be involved in its blockade. These residues were mapped and their contact and electrostatic interactions were evaluated revealing the influence of positive lysine residues and the additional contribution of an asparagine to the stabilization of the complex, bringing new insights into the mechanism of action of this toxin.
10.1016/j.jmgm.2018.11.012
pubmed_829_23551
Lipid peroxidation may be involved in cancer and essential nutrients that can scavenge free radicals, such as vitamins E and C, operate in concert. Levels of antioxidant vitamins E and C were estimated in 50 patients with oral cancer and 24 healthy persons served as control. Significantly lower levels of vitamins E and C were observed in oral cancer patients as compared to controls (P < 0.011). Antioxidant nutrients may be utilized to a greater extent in oral cancer patients to counteract free radical-mediated cell disturbances, resulting in a reduction in salivary antioxidant levels.
10.1179/135100007X200245
pubmed_27_19482
In this paper we present the first description of an anastomosis between both hypoglossal nerves during the embryonic period, a very uncommon anatomical variation. This was observed in a 30 mm crown-rump (C-R) length human embryo (Carnegie stage 23) from the Bellaterra Collection (Prof. Doménech Mateu), stained for nerve fibers. The anastomosis consisted of a large diameter trunk (36.7 microns) situated in front of and slightly below the hyoid cartilage, and clearly distinguishable from the anastomosis found in adults, which has a very fine diameter and is located in the suprahyoid region.
10.1007/BF00198324
pubmed_996_21394
This study examined preschool children's abilities to apply a newly learned organizational study-recall strategy in posttraining tasks that employed stimulus items from different media and that were administered by an unfamiliar experimenter. Forty-eight 4- and 5-year-old children were assigned to training and control conditions that alternated the presentation of pictures and objects on baseline, training, and test tasks. Same-medium tasks required children to study and recall items of the same stimulus medium (pictures or objects) as that depicting items in the training tasks. Different-medium tasks required performance with items presented in the alternate medium. Training included demonstration and practice in using a study-sorting strategy to organize the stimuli, encouragement to apply the strategy in new tasks, presenting a rationale for using the strategy, giving feedback about the effectiveness of using the strategy, and providing incentive for effortful performance. Subjects in the training groups showed marked increases in the use of sorting activities in posttraining tasks but failed to show corresponding significant improvements in item recall.
10.1080/00221309.1993.9711161
pubmed_538_18358
OBJECTIVE To measure the ventilation efficacy with three single-sized mask types on infant and child manikin models. METHODS Medical students were recruited as study subjects inasmuch as they are inexperienced resuscitators. They were taught proper bag-mask ventilation (BMV) according to the American Heart Association guidelines on an infant and a child manikin. Subjects completed a BMV attempt successfully using the adult standard mask (to simulate the uncertainty of mask selection), pocket mask, and blob mask. Each attempt consisted of 5 ventilations assessed by chest rise of the manikin. Study subjects were asked which mask was easiest to use. Four to six weeks later, subjects repeated the procedure with no instructions (to simulate an emergency BMV encounter without immediate pre-encounter teaching). RESULTS Forty-six volunteer subjects were studied. During the first attempt, subjects preferred the standard and blob masks over the pocket mask. For the second attempt, the blob mask was preferred over the standard mask, and few liked the pocket mask. Using the standard, blob, and pocket masks on the child manikin, 39, 42, and 20 subjects, respectively, were able to achieve adequate ventilation. Using the standard, blob, and pocket masks on the infant manikin, 45, 45, and 11 subjects, respectively, were able to achieve adequate ventilation. CONCLUSIONS Both the standard and blob masks are more effective than the pocket mask at achieving adequate ventilation on infant and child manikins in this group of inexperienced medical student resuscitators, who most often preferred the blob mask.
10.1016/j.ajem.2005.10.009
pubmed_179_122
In radioecological studies, there is a significant need for understanding the plant uptake of radionuclides on a cellular level. The present work applies mass spectrometry to image the radionuclide distribution within the cellular structures of plants at varying concentrations. In a first step, plants of Daucus carota and Pisum sativum labelled with iodine and rhenium were examined, at concentrations in the range of 10 mM. Cross sections of several plant parts were imaged by secondary ion mass spectrometry (SIMS) after cryogenation in order to preserve cell structure. In a second step, the distribution of 99Tc in the two plant species was determined. For radiological reasons, a concentration three orders of magnitude lower was used, rendering measurements with SIMS impossible. Therefore, resonant laser secondary neutral mass spectrometry (rL-SNMS) was used for the first time to image 99Tc with suppression of molecular isobaric interferences. The measurement of only about 1010 atoms of 99Tc atoms is demonstrated and the distribution of 99Tc within a single epidermal cell is imaged.
10.1016/j.jhazmat.2021.127143
pubmed_517_14671
Campylobacter is well recognized as the leading cause of bacterial foodborne diarrheal disease worldwide. Symptoms can range from mild to serious infections of the children and the elderly and permanent neurological symptoms. The organism is a cytochrome oxidase positive, microaerophilic, curved Gram-negative rod exhibiting corkscrew motility and is carried in the intestine of many wild and domestic animals, particularly avian species including poultry. Intestinal colonization results in healthy animals as carriers. In contrast with the most recent published reviews that cover specific aspects of Campylobacter/campylobacteriosis, this broad review aims at elucidating and discussing the (i) genus Campylobacter, growth and survival characteristics; (ii) detection, isolation and confirmation of Campylobacter; (iii) campylobacteriosis and presence of virulence factors; and (iv) colonization of poultry and control strategies.
10.3389/fmicb.2011.00200
pubmed_675_13608
INTRODUCTION Persistence of the left superior vena cava (LSVC) is a rare anatomical variant in the general population, with an estimated incidence of 0.3-0.5% in healthy individuals. It may be diagnosed incidentally after imaging control of the placement of a central venous catheter (CVC) or other device. PATIENT AND METHODS We present the case of a patient with acute disease who required central venous catheterization for the administration of intravenous chemotherapy. RESULTS Central venous catheterization proved difficult and imaging control revealed the catheter tip in an unusual position. Computed tomography to verify the catheter tip position revealed the presence of a persistent left superior vena cava. The patient then underwent the planned treatment with no complications associated with the CVC. CONCLUSION Although uncommon, persistence of the LSVC can have a significant impact in clinical practice, particularly when invasive procedures are required. Its recognition is important in order to minimize the potential complications inherent to such procedures. LEARNING POINTS Persistence of the left superior vena cava is an uncommon anatomical variant of the central venous vascular anatomy.It is generally asymptomatic, and its diagnosis is often incidentally made after certain procedures (central venous catheterization).Diagnosis through chest x-ray alone is difficult and should be complemented with transthoracic echocardiography and computed tomography in order to minimize the complications inherent to central venous catheterization.
10.12890/2021_002161
pubmed_584_20999
BACKGROUND/AIMS: To examine whether or not activated Kupffer cells play an important role in intra-hepatic Th1-associated necro-inflammation in Concanavalin A (Con A)-induced hepatic injury in mice. METHODS: Con A was administered to Balb/c mice pretreated with or without gadolinium chloride (GdCl(3)). Kupffer cell activation was evaluated by their ability to produce superoxide anions in situ under liver perfusion with nitro blue tetrazolium (NBT). Hepatic concentration of cytokines was measured by ELISA and the mRNA expression of CXC chemokine receptor 3 (CXCR3) was evaluated by RT-PCR. Immunohistochemical detection of CD4 positive lymphocytes in the liver was also performed. RESULTS: GdCl(3)-pretreatment significantly (P<0.01) reduced the serum levels of alanine aminotransferase (ALT) in Con A-treated mice. Formazan deposition in Kupffer cells, the hepatic concentration of tumor necrosis factor-alpha and interferon-gamma, the mRNA expression of CXCR3 and the CD4 positive lymphocytes in the liver were decreased in GdCl(3)-pretreated mice as compared with those without GdCl(3)-pretreatment (P<0.05, respectively). CONCLUSIONS: Activated Kupffer cells, which produce superoxide anions, are involved in Con A-induced hepatic necro-inflammation in mice possibly through the activation of Th1-associated immune response mediated by CD4 and/or CXCR3 positive cells recruited into the liver.
10.1016/s1386-6346(03)00206-7
pubmed_489_18773
OBJECTIVE To determine response rates (RR), progression-free survival (PFS), overall survival (OS), and toxicity in patients treated with cytotoxic chemotherapy, in combination with bevacizumab compared to cytotoxic chemotherapy alone, in the setting of recurrent ovarian cancer. MATERIALS AND METHODS After obtaining Institutional Review Board approval, two cohorts of patients with recurrent ovarian cancer were identified: 1) patients that received cytotoxic chemotherapy with bevacizumab from January 2006 to June 2009; 2) patients that received cytotoxic chemotherapy alone. RR were measured using RECIST criteria or by CA-125 levels using modified Rustin criteria. RR, OS, and PFS were determined using Kaplan-Meier survival analysis. RESULTS Thirty-two patients that received bevacizumab in combination with cytotoxic chemotherapy and 32 patients that received cytotoxic chemotherapy alone were identified. The control patients were matched for age, platinum response, histology, surgical outcome, grade, and number of previous chemotherapy regimens. There were no differences between the two cohorts in the rates of venous thromboembolism (VTE) (p = 0.39), bleeding (p = 0.15) or bowel obstruction (p = 0.40). The rate of hypertension in the bevacizumab cohort was greater than in the comparison cohort (p < 0.005). There were no differences in response rates PR/CR vs SD/PD (p = 0.46), OS (p = 0.79) or PFS (p = 0.43). CONCLUSIONS With increased toxicity, increased cost of therapy and no improvement in PFS or OS, the role of bevacizumab in patients with recurrent ovarian cancer warrants further investigation.
pubmed_489_18773
pubmed_757_4131
Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigonella foenum graecum) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba, and Rhizoma polygonati, is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.
10.2147/DMSO.S326054
pubmed_203_7388
This study examined interest in genetic testing for lung cancer susceptibility among college students, a group whose smoking rates have increased significantly in the last decade. Sixteen smokers who participated in focus group discussions indicated a generally high level of interest in testing. They also indicated that knowledge of genetic susceptibility would make them feel anxious and motivate them to quit smoking. The study also examined, in a separate sample of undergraduate smokers (n=186), whether these outcomes depend on personality differences in threat sensitivity-responsiveness of the behavioral inhibition system (BIS)--and reward sensitivity--responsiveness of the behavioral activation system (BAS). Smokers completed measures of personality and risk perceptions at baseline and rated risk perceptions, affect, and likelihood of changing smoking behavior in response to 2 hypothetical risk feedback scenarios (high vs. low risk). Smokers higher in reward sensitivity (reward responsiveness) evidenced greater interest in taking genetic tests. If a test indicated elevated risk smokers higher in reward responsiveness would perceive themselves at increased risk and attempt to quit smoking. Threat sensitive smokers would react with greater negative affect. Overall, results indicate that genetic biomarker feedback is a motivator for college student smokers to quit and would be more effective among smokers high in reward sensitivity.
10.1016/j.addbeh.2005.03.002
pubmed_217_20458
Light food and beverages are increasing on the market for many years, first for economic reasons and, more and more for aesthetisme, however without aimed a defined population. The interest of these products is not evident, reason why it is difficult to get a clear and objective opinion without being influenced by marketing messages. Under what circumstances can they be a solution? Can we advise them? Do they have an influence in the loss or weight control? This article offers some thoughts and suggestions on the use of these specific products.
pubmed_217_20458
pubmed_263_18890
Physalis alkekengi has been traditionally used for the treatment of coughs, middle ear infections, and sore throats in Korea, Europe, and China. It exhibits a variety of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-cancer effects. The anti-inflammatory effects of the P. alkekengi methanol extract (PA) and its molecular mechanisms have not yet been fully investigated. In the present study, the chromatogram of PA was established by UPLC analysis. The anti-inflammatory effects of PA were also investigated using murine microphage cell lines, RAW 264.7 cells, and a murine model of OVA induced asthma. In LPS-stimulated RAW264.7 cells, PA reduced the MMP-9 expression with decreases in the production of nitric oxide, inteleukin-6, and tumor necrosis factor-α. Furthermore, PA suppressed the phosphorylation of MAPKs, which resulted in the inhibition of AP-1 activation. These effects of PA were consistent with the results of the in vivo experiment. PA-treated mice significantly inhibited inflammatory cell counts and cytokine production in bronchoalveolar lavage fluids and airway-hyperresponsiveness in OVA-induced asthmatic mice. PA treated mice also showed a marked inhibition of inducible nitric oxide synthase and MMP-9 expression. In conclusion, our results suggest that PA may be a valuable therapeutic material in treating various inflammatory diseases, including allergic asthma.
10.1016/j.imbio.2014.10.004
pubmed_827_12498
The dynamics of an elongated attractive Bose-Einstein condensate in an axisymmetric harmonic trap is studied. It is shown that density fringes caused by self-interference of the condensate order parameter seed modulational instability. The latter has novel features in contradistinction to the usual homogeneous case known from nonlinear fiber optics. Several open questions in the interpretation of the recent creation of the first matter-wave bright soliton train [Nature (London) 417, 150 (2002)]] are addressed. It is shown that primary transverse collapse, followed by secondary collapse induced by soliton-soliton interactions, produces bursts of hot atoms at different time scales.
10.1103/PhysRevLett.92.040401
pubmed_371_13780
In addition to the known Sertoli-cell processes, processes of the mouse spermatid's cytoplasm are found to invaginate neighbouring spermatids. Surrounded by the adjacent Sertoli process, the spermatid processes form a "spermatid-Sertoli cell process". They are observed between spermatids at the same step or at different steps of their development and degenerate mostly at step 13 to 15 of spermiogenesis. Whether these structures are related to either spermatid exchanges or connections or participate to cytoplasm elimination is discussed.
10.1016/0248-4900(91)90277-t
pubmed_660_17950
OBJECTIVE To observe the effect of cholesterol on phenotypic switching of human vascular smooth muscle cells (VSMCs) in vitro. METHODS VSMCs were treated with cholesterol at 12.5, 25.0 and 50.0 mg/L for 48 hours and at 50 mg/L for 24, 48 and 72 hours. Real-time quantitative PCR and Western blotting were respectively applied to detect the mRNA expressions of smooth muscle alpha-actin (α-SMA), smooth muscle 22 alpha (SM22α) and the protein expressions of SM22α, monocyte chemotactic protein-1 induced protein (MCPIP). CCK-8 assay was performed to analyze the viability of VSMCs. RESULTS Compared with control groups, cholesterol treatments resulted in a significant down-regulation of both mRNA and protein expressions of endogenous α-SMA and SM22α in VSMCs at 48 hours (P<0.05), and the expressions were lowest when cholesterol was 50.0 mg/L. At 48 and 72 hours, 50.0 mg/L cholesterol significantly decreased the expressions of α-SMA and SM22α (P<0.05). The proliferation of VSMCs in cholesterol groups was promoted significantly compared with control groups (P<0.05). Cholesterol at 50.0 mg/L was also able to induce MCPIP protein expression in VSMCs at 48 hours (P<0.05). CONCLUSION Cholesterol can decrease the expressions of α-SMA and SM22α and enhance the proliferation of VSMCs, which suggests that cholesterol induces phenotypic switching of VSMCs.
pubmed_660_17950
pubmed_1082_12179
In this paper we outline a cognitive model of Obsessive-Compulsive Disorder (OCD) which proposes that the core belief of OCD evolves through a series of illogical inferences. These faulty inference processes involve inferring the plausibility of events on the basis of irrelevant associations, dismissing actual evidence on the grounds of going beyond surface reality to a deeper reality, and finally inferring that a completely fictional narrative is a remote probability. A therapy aimed specifically at changing these inference processes is illustrated with case examples of OCD clients who had not benefited from conventional behavior therapy. The inference based approach (IBA) complements existing cognitive-behavioral therapy but suggests that in certain cases, the conventional cognitive therapy view of OCD beliefs as exaggerated fears of remote possibilities may actually reinforce the obsessional belief since even remote events are real. The IBA on the contrary suggests that an important goal in therapy is to highlight this confusion found in OCD between imagination and reality and illuminate for the OCD client how their compulsions, far from reassuring them about a remote possibility, actually take them further away from reality and reinforce their imaginary doubt.
10.1016/0005-7967(95)00042-v
pubmed_355_12363
The hapten/class I MHC-specific soluble immunoregulatory molecules produced by CD8+T cells from dinitrobenzene sulfonate-primed mice express the binding specificity and serologic determinants of alpha/beta TCR. To examine the genes used to encode these soluble immunoregulatory molecules, we utilized a surface TCR expressing Ts hybridoma, which constitutively produces a DNP/Kd-specific regulatory molecule. Northern and Southern analyses indicated that MTs 79.1 cells use a V beta 8 and a V alpha 4 gene to encode the variable regions of the surface alpha/beta TCR. A panel of TCR- variants was generated by subjecting MTs 79.1 cells to gamma-irradiation. Twelve of the TCR- variants were chosen for detailed characterization. Northern blot analyses indicated the absence of the MTs 79.1 V alpha 4 chain transcript in five of the variants and the absence of the parental V beta 8 chain transcript in the other seven. Southern blot analyses demonstrated the deletion of the parental gene encoding the alpha- or beta-chain from the genome of the respective mutant. None of the 12 TCR gene deletion mutants produced the parental suppressive activity. Expression of the parental TCR beta-chain gene in one of the beta-chain gene deletion mutants reconstituted the ability to produce this activity. As with the MTs 79.1 molecule, the regulatory molecule produced by the beta-chain gene transfectant was bound by and eluted from Sepharose columns coupled with either DNP or anti-V beta 8 antibodies. These results establish a strong linkage between the suppressor molecules produced by these Ts and TCR alpha- and beta-chain gene transcription.
pubmed_355_12363
pubmed_163_12832
Targeting the key enzymes of sphingolipid metabolism including serine palmitoyltransferase (SPT), sphingosine kinase (SK) and glucosylceramide synthase (GCS) has a therapeutic importance. However, sphingolipid metabolism-mediated anti-leukemic actions of resveratrol in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Therefore, we explored potential mechanisms behind resveratrol-mediated cytotoxicity in SD1 and SUP-B15 Ph + ALL cells in the context of sphingolipid metabolism and apoptosis induction. The anti-proliferative and apoptotic effects of resveratrol alone and in combination with SPT inhibitor (myriocin), SK inhibitor (SKI II), GCS inhibitor (PDMP) were determined by MTT cell proliferation assay and flow cytometry, respectively. The effects of resveratrol on PARP cleavage, SPT, SK and GCS protein levels were investigated by Western blot. Resveratrol inhibited proliferation and triggered apoptosis via PARP activation and externalization of phosphatidylserine (PS). Resveratrol increased the expression of SPT whereas it downregulated SK and GCS. Resveratrol's combinations with SKI II and PDMP intensified its anti-leukemic activity by increasing the relocalization of PS while its combination with myriocin suppressed apoptosis. Therefore, resveratrol inhibited cell proliferation and induced apoptosis through modulating SK, GCS and SPT expression, which may be considered as novel biomarkers of resveratrol-induced cytotoxicity in Ph + ALL.
10.1080/01635581.2021.2005806
pubmed_135_11737
O-GlcNAcylation is an atypical, dynamic and reversible O-glycosylation that is critical and abundant in metazoan. O-GlcNAcylation coordinates and receives various signaling inputs such as nutrients and stresses, thus spatiotemporally regulating the activity, stability, localization and interaction of target proteins to participate in cellular physiological functions. Our review discusses in depth the involvement of O-GlcNAcylation in the precise regulation of skeletal muscle metabolism, such as glucose homeostasis, insulin sensitivity, tricarboxylic acid cycle and mitochondrial biogenesis. The complex interaction and precise modulation of O-GlcNAcylation in these nutritional pathways of skeletal muscle also provide emerging mechanical information on how nutrients affect health, exercise and disease. Meanwhile, we explored the potential role of O-GlcNAcylation in skeletal muscle pathology and focused on its benefits in maintaining proteostasis under atrophy. In general, these understandings of O-GlcNAcylation are conducive to providing new insights into skeletal muscle (patho) physiology.
10.3390/metabo12100888
pubmed_999_24213
BACKGROUND Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. METHODS Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. RESULTS A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. CONCLUSIONS For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.
10.1186/s12876-021-01788-4
pubmed_774_13376
Schwann cells are the main supportive cells of the peripheral nerves. Schwann cells suffer inhibition of autophagy under hyperglycemia treatment in diabetic peripheral neuropathy (DPN). However, the exact mechanism is still not fully elucidated. We first observed the decrease of autophagy markers (LC3-II/LC3-I, P62) in the sciatic nerves of diabetic mice vs. normal mice, accompanied with the loss of myelinated nerve fibers and abnormal myelin sheath. In line with this, LC3-II/LC3-I and P62 were also significantly reduced in high glucose-treated rat Schwann cell 96 (RSC96) cells compared with normal glucose-treated cells. Furthermore, we found that trichostatin A [an inhibitor of histone deacetylase (HDAC)] evidently improved LC3-II/LC3-I in high glucose-treated RSC96 cells, without an effect on P62 expression. Again, HDAC1 and HDAC5 were revealed to be increased in RSC96 cells stimulated with high glucose. Inhibition of HDAC1 but not HDAC5 by small hairpin RNA vector enhanced LC3-II/LC3-I in high glucose-cultured RSC96 cells. In addition, LC3-II conversion regulators [autophagy-related protein (Atg)3, Atg5, and Atg7] were detected in high glucose-treated and HDAC1-knockdown RSC96 cells, and Atg3 was proven to be the key target of HDAC1. The presuppression of Atg3 offset the improvement of LC3-II/LC3-I resulting from HDAC1 inhibition in high glucose-treated RSC96 cells. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway was activated in RSC96 cells treated with high glucose, which was indicated by increased STAT3 phosphorylation. Blocking STAT3 phosphorylation by chemical inhibitor AG490 induced HDAC1 down-regulation followed by increases in Atg3 and LC3-II/LC3-I. Interestingly, we also found that AG490 treatment enhanced P62 expression in high glucose-stimulated RSC96 cells. Taken together, our findings demonstrate that hyperglycemia inhibits LC3-II/LC3-I in an HDAC1-Atg3-dependent manner and decreases P62 expression in an HDAC-independent manner via the JAK-STAT3 signaling pathway in the Schwann cells of DPN.-Du, W., Wang, N., Li, F. Jia, K., An, J., Liu, Y., Wang, Y., Zhu, L., Zhao, S. Hao, J. STAT3 phosphorylation mediates high glucose-impaired cell autophagy in an HDAC1-dependent and -independent manner in Schwann cells of diabetic peripheral neuropathy.
10.1096/fj.201900127R
pubmed_990_1360
The diagnosis of diffuse type gastric carcinoma is very difficult. The delay of diagnosis is often due to false-negative endoscopic and histologic evaluation. The architecture of the stomach can be clearly visualized by endosonography. Therefore, already minor destructions of the gastric layers can be found. The endosonographic picture includes the presence of the layers, which are larger and of irregular contour. In infiltrating gastric cancer typically the submucosal layer and the muscularis are concentrically enlarged and appear folded. Based on the endosonographic picture diffuse type gastric carcinoma has been diagnosed in 32 patients. When compared to the histologic diagnosis after gastrectomy or autopsy the accuracy of the endosonographic diagnosis was 87.5%, (28 out of 32 patients). From the remaining four patients diagnosed to have diffuse type gastric cancer by endosonography three patients turned out to have malignant infiltrating tumors of different histologies. Therefore, the positive predictive value of endosonography in detection of infiltrating malignant tumors was 96.8% in our group. In contrast the accuracy of preoperative histologic diagnosis by biopsies was only 58%. Suspicious results of gastroscopy, especially in combination with a negative biopsy, should lead to further evaluation by endosonography to detect diffuse type gastric cancer earlier.
pubmed_990_1360
pubmed_183_18959
Herpes simplex viruses (HSV) harness cellular calcium signaling pathways to facilitate viral entry. Confocal microscopy and small interfering RNA (siRNA) were used to identify the source of the calcium and to dissect the requisite viral-cell interactions. Binding of HSV to human epithelial cells induced no calcium response, but shifting the cells to temperatures permissive for penetration triggered increases in plasma membrane calcium followed by a global release of intracellular calcium. Transfection with siRNA targeting the proteoglycan syndecan-2 blocked viral binding and abrogated any calcium response. Transfection with siRNA targeting nectin-1, a glycoprotein D receptor, also prevented both membrane and intracellular calcium responses. In contrast, the membrane response was preserved after transfection with siRNA targeting integrinalphav, a novel glycoprotein H receptor. The membrane response, however, was not sufficient for viral entry, which required interactions with integrinalphav and release of inositol-triphosphate receptor-dependent intracellular calcium stores. Thus, calcium plays a critical, complex role in HSV entry.
10.1091/mbc.e07-01-0062
pubmed_506_17287
A large number of tendon repair techniques have been described for acute tendon injury. However, after reviewing the literature, it was noted that there were limited descriptions of specific suture techniques that address repair processes of chronic tendon pathology. Generally, in chronic tendinopathy, others have described a process known as tendon tubularization, which consists of a running stitch using a nonabsorbable suture material along the external surface of the tendon. We believe that leaving a nonabsorbable suture on the exterior surface of the tendon in this manner has the potential to disrupt the optimal gliding function. Furthermore, because additional damage could be present within the body of the tendon, this form of repair might not prove adequate to optimally appose the disrupted tendon segments internally. We have described a simple technique to repair chronic tendon injury from "the inside-out." We believe this approach provides better augmentation of tendon strength and eliminates the nonabsorbable suture along the exterior surface of the tendon.
pubmed_506_17287
pubmed_844_17961
The Na(+)-bile acid cotransporters NTCP and ASBT are largely responsible for the Na(+)-dependent bile acid uptake in hepatocytes and intestinal epithelial cells, respectively. This review discusses the experimental methods available for demonstrating electrogenicity and examines the accumulating evidence that coupled transport by each of these bile acid transporters is electrogenic. The evidence includes measurements of transport-associated currents by patch clamp electrophysiological techniques, as well as direct measurement of fluorescent bile acid transport rates in whole cell patch clamped, voltage clamped cells. The results support a Na+:bile acid coupling stoichiometry of 2:1.
pubmed_844_17961
pubmed_503_11411
Clinical trials with tizanidine when administered alone have shown that 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiodiazole (tizanidine) is safe and effective for spasticity control. However, given its mechanism of action and requirement for titration, clinical experience suggests that tizanidine is likely to be used in combination with other antispastic agents with different mechanisms of action, such as baclofen. The objective of this study was to examine the pharmacokinetics of both tizanidine and baclofen under steady-state conditions when administered alone or concomitantly. This was a randomized, three-period, multiple-dose, Latin Square design study consisting of tizanidine HCl, 4 mg t.i.d. for seven consecutive doses; baclofen, 10 mg t.i.d. for seven consecutive doses; and both regimens simultaneously for seven consecutive doses. Drug administration was performed every 8 h, three times daily. Fifteen normal men served as study subjects. A priori, a clinically significant difference was set as 30%. Concentrations of tizanidine and baclofen were nearly identical during the single and concomitant dosing periods. All of the calculated steady-state pharmacokinetic parameter changes for baclofen, tizanidine, and its major metabolites were within the 30% criterion. Small differences in renal clearance were observed when the two drugs were coadministered, but these changes are unlikely to be clinically important. Thus, it is unlikely that coadministration of tizanidine and baclofen during dose-titration of the former will result in a pharmacokinetic interaction.
pubmed_503_11411
pubmed_323_278
OBJECTIVE To discuss the diagnosis and management of venous original pulsatile tinnitus associated with sigmoid sinus. METHODS A retrospective study was conducted on 12 patients who were diagnosed with venous original pulsatile tinnitus associated with sigmoid sinus, and treated with sigmoid sinus constriction surgery. The diagnostic evidences for venous original pulsatile tinnitus associated with sigmoid sinus were re-evaluated, the pulsatile tinnitus improvements and MRV study results before and after surgeries associated with sigmoid sinus were compared. RESULTS Eleven patients got relief of tinnitus within three months after the surgeries, while one patient had no relief. There were ten patients underwent MRV study, the cross-sectional area of the sigmoid sinus in the healthy side was about two times in the tinnitus side. Constriction sigmoid sinus was performed on the twelve patients. The cross-sectional area of the sigmoid sinus of relieved tinnitus patients were compressed by forty-six percent to eighty-three percent. None of the cases complained of any serious complications. CONCLUSIONS Sigmoid sinus constriction is an available therapy for pulsatile tinnitus at present. More cases and longer follow-up are necessary to evaluate its treatment effect accurately.
pubmed_323_278
pubmed_664_7002
Signaling by the small G-protein Rap is under tight regulation by its GEFs and GAPs. These are multi-domain proteins that are themselves controlled by distinct upstream pathways, and thus couple different extra- and intracellular cues to Rap. The individual RapGEFs and RapGAPs are, in addition, targeted to specific cellular locations by numerous anchoring mechanisms and, consequently, may control different pools of Rap. Here, we review the various activating signals and targeting mechanisms of these proteins and discuss their contribution to the spatiotemporal regulation and biological functions of the Rap proteins.
10.1016/j.tcb.2011.07.001
pubmed_408_6416
Three cases of aplastic and/or hypoplastic lumbar pedicle are presented and discussed. The importance of plain films, especially the 45 degrees posterior oblique, for making the diagnosis is emphasized. The incidence and embryology of abnormalities of the pedicle are reviewed and the radiological features used to differentiate these congenital abnormalities from neoplasm and trauma are described.
10.1007/BF00342070
pubmed_28_20911
In this study, we present a mathematical model of dengue fever transmission with hospitalization to describe the dynamics of the infection. We estimated the basic reproduction number for the infected cases in East Java Province for the year 2018 is . The parameters of the dengue model are estimated by using the confirmed notified cases of East Java province, Indonesia for the year 2018. We formulated the model for dengue with hospitalization and present its dynamics in details. Initially, we present the basic mathematical results and then show briefly the stability results for the model. Further, we formulate an optimal control problem with control functions and obtain the optimal control characterization. The optimal control problem is solved numerically and the results comprised of controls system for different strategies. The controls such as prevention and insecticide could use the best role in the disease eradication from the community. Our results suggest that the prevention of humans from the mosquitoes and the insecticide spray on mosquitoes can significantly reduce the infection of dengue fever and may reduce further spread of infection in the community.
10.1016/j.heliyon.2021.e06023
pubmed_348_12583
Autoreactive B cells are prevented from producing autoantibodies that may cause pathogenicity in autoimmune diseases by the induction of tolerance. When autoreactive B cells escape regulation in autoimmune-prone individuals, large amounts of autoantibodies are produced with somatic mutations in their variable regions. In this issue of the European Journal of Immunology, a new and very useful model is presented that induces activation and hypermutation of autoreactive B cells upon injection of chromatin-containing immune complexes. The differentiation and hypermutation of autoreactive B cells takes place at extrafollicular sites.
10.1002/eji.200737971
pubmed_162_1243
Monocarboxylate transporters (MCT) are transmembrane proteins that control the lactate metabolism and are associated with poor prognosis in solid tumors, including colorectal cancer. Here, we aimed to investigate the biological and clinical role of MCTs in colorectal cancer and to assess the potential of therapeutic application. A total of 16 human colorectal cancer cell lines, 11 patient-derived cells from malignant ascites [patient-derived cells (PDC)], and 39 matched pairs of primary colorectal cancer and normal colorectal tissues were used to assess the role of MCT in vitro and in vivo siRNA methodology was used to determine the effect of MCT inhibition and molecular mechanism of hypoxia- and angiogenesis-related factors in addition to MCT4. The effect of MCT inhibition was confirmed in mouse xenograft models. MCT4 expression in surgical tissue was evaluated by IHC and used for survival analysis. Expression of MCTs was demonstrated in colorectal cancer cell lines. siRNA-mediated MCT silencing caused significant decline of cell proliferation both in vitro and in vivo An additive effect of MCT inhibition was induced by combined treatment with chemotherapy or radiotherapy. In particular, the expression of MCT4 was markedly increased in PDCs, and MCT4 inhibition significantly decreased PDC proliferation. Hypoxia-inducible factor 1-α (HIF1α) was also highly expressed in PDCs, whereas HIF1α knockdown reduced MCT4 expression and of other angiogenesis-related mediators. The patients with high MCT4 expression by IHC showed shorter relapse-free survival compared with low expression. These findings suggest that MCT4 may represent a new therapeutic target for colorectal cancer with peritoneal carcinomatosis and serve as a prognostic indicator. Mol Cancer Ther; 17(4); 838-48. ©2018 AACR.
10.1158/1535-7163.MCT-17-0535
pubmed_825_19751
In experimental animal models nonsteroidal anti-inflammatory drugs may influence gastrointestinal motility, but as evidence is lacking in man. The effect of diclofenac sodium 75 mg i.m. on the motor response of the upper gastrointestinal tract to food has been studied by manometry in 9 healthy volunteers. Diclofenac had no effect on the motor activity of the stomach, duodenum, or jejunum after a 605 kcal meal.
10.1007/BF00626379
pubmed_51_7778
UNLABELLED What's known on the subject? and What does the study add? Ovary hormone deficiency and the age-related changes in post-menopausal women are subjected to a number of urological dysfunctions, including overactive bladder syndrome. Green tea is a popular healthy drink worldwide and its extract catechin has strong anti-inflammatory and antioxidant properties. EGCG, the major type of catechin, is an antioxidant polyphenol flavonoid isolated from green tea. EGCG supplement could prevent ovariectomy-induced bladder dysfunction in a dose-related manner through its anti-oxidant, anti-fibrosis and anti-apoptosis effects. OBJECTIVE To evaluate whether green tea extract, epigallocatechin gallate (EGCG), could prevent ovariectomy-induced overactive bladder (OAB) and to investigate its antioxidant, anti-apoptotic and anti-fibrosis effects. MATERIALS AND METHODS In all, 48 female Sprague-Dawley rats were divided into four groups. After bilateral ovariectomy, the first group served as the ovariectomy control, the second group received EGCG 1 µM/kg daily i.p. injection after ovariectomy surgery, and the third group received EGCG 10 µM/kg daily i.p. injection. The fourth group was taken as the sham without ovariectomy surgery. The rats were killed after 6 months after ovariectomy surgery. Cystometrograms were performed for the measure of bladder overactivity. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was used to evaluate apoptotic cells. Western immunoblots were performed to determine the expressions of inflammatory markers, apoptosis-associated proteins and oxidative stress markers. RESULTS Long-term ovariectomy significantly increased non-voiding contractions and decreased bladder compliance. Treatment with EGCG significantly increased bladder compliance and diminished non-voiding contractions. Ovariectomy significantly increased apoptotic cells and enhanced interstitial fibrosis in bladders. The expression of caspase-3 significantly increased, while that of Bcl-2 notably decreased after ovariectomy. Inflammatory and fibrosis markers, TGF-β, fibronectin and type I collagen expressions were significantly increased after 6 months of ovariectomy surgery. Treatment with EGCG significantly decreased TGF-β and type I collagen expressions. Oxidative stress markers, nitrotyrosine and protein carbonylation levels were significantly increased in the ovariectomy group. EGCG could attenuate this oxidative damage in dose-dependent fashion. CONCLUSIONS Ovariectomy increased oxidative damage, enhanced voiding frequency and decreased bladder compliance. EGCG could restore ovariectomy-induced bladder dysfunction in a dose-dependent fashion through antioxidant, anti-fibrosis and anti-apoptosis effects.
10.1111/j.1464-410X.2012.11258.x
pubmed_758_7897
OBJECTIVE To review the literature regarding the management of asymptomatic bacteriuria (ASB) in patients with diabetes mellitus. DATA SOURCES A MEDLINE (1967-June 2003) and bibliographic search of the English-language literature was conducted using the search terms diabetes mellitus, asymptomatic, bacteriuria, and urinary tract infection. DATA SYNTHESIS ASB occurs in diabetic women more commonly than in non-diabetics and is associated with an increased risk of symptomatic urinary tract infection (UTI) among patients with type 2 diabetes. Symptomatic UTIs tend to follow a more complicated course in diabetics. Despite these independent observations, antimicrobial therapy has not been shown to reduce symptomatic UTIs, pyelonephritis, or hospitalization for UTI. CONCLUSIONS Available evidence does not support antimicrobial treatment of ASB among patients with diabetes mellitus.
10.1345/aph.1D355
pubmed_1123_10206
Despite the large body of literature describing the synthesis of magnetic nanoparticles, few analytical tools are commonly used for their purification and analysis. Due to their unique physical and chemical properties, magnetic nanoparticles are appealing candidates for biomedical applications and analytical separations. Yet in the absence of methods for assessing and assuring their purity, the ultimate use of magnetic particles and heterostructures is likely to be limited. In this review, we summarize the separation techniques that have been initially used for this purpose. For magnetic nanoparticles, it is the use of an applied magnetic flux or field gradient that enables separations. Flow based techniques are combined with applied magnetic fields to give methods such as magnetic field flow fractionation and high gradient magnetic separation. Additional techniques have been explored for manipulating particles in microfluidic channels and in mesoporous membranes. Further development of these and new analytical tools for separation and analysis of colloidal particles is critically important to enable the practical use of these, particularly for medicinal purposes.
10.1039/c2cp22982j
pubmed_1042_2049
Pig cryptorchidism is a congenital anomaly, which requires surgical intervention. Pain assessment in pig farming has some limitations and consumers are increasingly concerned about suffering linked to on-farm procedures. The PGS seems to be a promising tool for pain assessment in piglets, although it has not been investigated whether this tool is applicable to growing pigs. This study was designed to determine whether the PGS could be useful to assess pain in growing pigs undergoing on-farm cryptorchidectomy. Ten mixed-breed cryptorchid pigs were pre-medicated with azaperone and ketamine. Anesthesia was induced and maintained using IV sodium based. Pigs were filmed pre- and 6 h post-surgery to evaluate their behavior (scan sampling every minute). Besides, 36 pictures of the face expressions (18 pre- and 18 6 h post-surgery) were scored with the PGS by three treatment-blind observers. The pre-surgery pig's activity ratio was 59%, while it was 2% 6 h post-surgery. While the PGS inter-observer reliability was excellent (Interclass Correlation Coefficient value of 0.87), the PGS score increased significantly in pigs 6 h post-surgery (Paired sample t-test, p = 0.02). The PGS proved to be a potentially effective method to assess pain associated with cryptorchidectomy. However, further validation studies are required to validate this tool for other potentially painful procedures.
10.3390/ani10030412
pubmed_744_10168
F165(1) (foo) and CS31A (clp) are bacterial adhesins synthesized by Escherichia coli strains associated with diarrhea and septicemia in piglets and calves. They belong to the P-regulatory family and as such are subject to a phase variation control mediated by Lrp (leucine responsive regulatory protein) and regulators homologous to PapI. Analysis of expression of transcriptional fusions between the fooB or fooI promoters and lacZ showed that Lrp is an activator of foo and fooI transcription, whereas it represses clp transcription. Furthermore, foo phase variation leads to a large majority of phase-ON cells, whereas clp phase variation leads to a majority of phase-OFF cells. We compared the influence of several environmental cues on foo and clp expression, with special attention to the effects of leucine and alanine known to be mediated by Lrp. Inhibition or significant repression of foo and clp transcription was observed at low temperature, in LB medium, and in the presence of glucose, alanine, or leucine. Glucose repression of foo but not of clp was totally relieved by addition of cAMP. Osmolarity and pH had little effect. Alanine but not leucine, and LB medium inhibited foo and clp phase variation, locking cells in the OFF phase. Low temperature inhibited clp phase variation and altered the switch frequency of foo phase variation, leading to more phase-OFF cells. Glucose altered the phase variation of both operons, increasing the number of phase-OFF cells in the population. The regulation pattern of foo and clp is consistent with F165(1) and CS31A production in low nutrient environments, even at moderately acidic pH or high osmolarity.
10.1016/j.resmic.2004.02.005
pubmed_661_14110
Since previous studies have suggested that the mammalian protamine mRNAs are translated poorly in cell-free systems, we directly measured the efficiency of translation of mouse protamine 1 mRNA. We found that mouse testis poly(A)+ mRNA stimulates the synthesis in the wheat germ and reticulocyte cell-free systems of three prominant translation products which can be resolved by electrophoresis through acid urea polyacrylamide gels containing 8 M urea. These translation products have been identified as testis-specific protein, protamine 1, and the precursor to protamine 2 by several criteria, including labeling with amino acids, [35S]cysteine, and [3H]leucine, which are known to be specific to some of these proteins from the nucleotide sequences of recombinant DNAs. Surprisingly, the mobility of the testis-specific protein translation product is slightly reduced and the mobility of both protamine translation products is drastically reduced unless the extracts of cell-free translations are coelectrophoresed with the appropriate carrier. The fraction of [35S]cysteine- labeled protamine 1 translation product was compared with the fraction of testis poly(A)+ mRNA as protamine 1 mRNA which we measured in dot blots with the use of an SP6 RNA polymerase transcript for protamine 1. The results demonstrate that protamine 1 mRNA is translated only slightly less efficiently than the average testis poly(A)+ mRNA.
10.1016/0012-1606(87)90434-9
pubmed_443_13107
Insulin and four peptides derived from the posttranslational processing of proglucagon have been isolated in pure form from the pancreas of the cane toad, Bufo marinus. Although Bufo insulin contains 9 amino acid substitutions, compared with human insulin, all those residues that are considered to be involved in receptor-binding and in dimer and hexamer formation have been conserved. Bufo insulin was, however, more potent (4-fold) than human insulin in inhibiting the binding of [125I-Tyr-A14] insulin to the soluble full-length recombinant human insulin receptor, which is probably a consequence of the substitution (Thr --> His) at position A-8. Bufo glucagon was isolated in two molecular forms: glucagon-29 shows only one amino acid substitution (Thr29 --> Ser), compared with human glucagon; and glucagon-36 comprises glucagon-29, extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Met-Ser. The human proglucagon gene contains one copy of glucagon-like peptide (GLP)-1, a potent insulin secretogogue, and one copy of GLP-2 that is devoid of insulin-releasing activity. In contrast, two proglucagon-derived peptides with 32- and 37-amino acid residues (GLP-32 and GLP-37), displaying greater structural similarity to human GLP-1 than to GLP-2, were isolated from Bufo pancreas. Both peptides produced concentration-dependent increases in insulin release from glucose-responsive rat insulinoma-derived BRIN-BD11 cells. The threshold concentrations producing a significant (P < 0.001) effect were 10(-8) M (GLP-32) and 10(-9) M (GLP-37), and the maximum increase in the rate of insulin release produced by 10(-6) M concentrations of both peptides was approximately 5-fold.
10.1210/endo.139.8.6139
pubmed_787_5795
Microcystins are cyanobacterial hepatotoxins capable of accumulation into animal tissues. The toxins act by inhibiting specific protein phosphatases and both non-covalent and covalent interactions occur. The 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB) method determines the total, i.e. the sum of free and protein-bound microcystin in tissues. The aim of the method development in this paper was to tackle the problems with the MMPB methodology: the rather laborious workflow and the loss of material during different steps of the method. In the optimised workflow the oxidation recovery was of acceptable level (29-40%), the extraction efficiency good (62-97%), but the signal suppression effect from the matrix remained severe in our system (16-37% signal left). The extraction efficiency for the determination of the free, extractable microcystins, was found to be good, 52-100%, depending on the sample and the toxin variant and concentration.
10.1016/j.envpol.2009.10.023
pubmed_443_12954
Autonomous expression of progesterone receptors (PR) in human meningiomas is well established. To evaluate whether, similar to progesterone receptors, other estrogen-inducible proteins are also autonomously expressed in meningiomas, concentrations of pS2 and cathepsin-D (Cath-D) were measured in 52 meningiomas. No pS2 protein was detectable in 52/52 tested meningiomas. The Cath-D protein was measurable in all 52 meningiomas, but the mean concentration of Cath-D in meningioma cytosols was 2.4-fold lower than that of a group of 54 breast tumors (p < 0.001). These results indicate that autonomous expression is a PR-related rather than an estrogen receptor-related phenomenon and, consequently, that estradiol is probably not responsible for PR synthesis in human meningiomas. To evaluate the role of other, non-estradiol-dependent signalling pathways in PR synthesis, the effects of EGF, Forskolin and phorbol ester on PR synthesis were tested in vitro. No PR was detectable after the addition of EGF to six different primary cultures. Forskolin and TPA addition caused a morphological change in meningioma cells, but did not induce PR or pS2 synthesis in two different primary meningioma cultures. We conclude that PR synthesis in human meningiomas cannot be triggered by switching on the signalling pathways activated by these growth factors.
10.1177/172460089801300104
pubmed_57_7147
Solid dispersion technique is known to be an effective approach for the polymer to keep drugs stable in the solid state, thereby improving the dissolution rate and oral bioavailability through inhibiting reprecipitation in supersaturated solution. In this study, to evaluate the inhibitory effect of polyethylene glycol-6000 (PEG), Polyvinylpyrrolidone K30 (PVP) and Aminoalkyl methacrylate copolymer (Eudragit), the reprecipitation profiles were observed from supersaturated solutions of Patchouli alcohol (PA) in the presence and absence of the polymers. Furthermore, the dissolution profiles of PA solid dispersions formulated with PEG, PVP or Eudragit were compared for investigating the effect on improving dissolution of each polymer. Solid dispersions formulated with Eudragit were found to result in solution with the highest extent of supersaturation. By contrast, PEG and PVP were less effective. At equivalent supersaturation, all three polymers are capable of mitigating reprecipitation relative to that of PA alone. In addition, in the PA solid dispersion with Eudragit (E-SD (1/3)), the highest concentration of supersaturation of PA was maintained for prolonged time. These results unambiguously indicate that it is imperative to select the appropriate polymer and drug/polymer ratio in addition to considering the stability of the supersaturated solution, which was generated following dissolution of amorphous solid dispersion.
10.3109/03639045.2013.877482
pubmed_3_14998
In this paper we propose a boosting approach to random subspace method (RSM) to achieve an improved performance and avoid some of the major drawbacks of RSM. RSM is a successful method for classification. However, the random selection of inputs, its source of success, can also be a major problem. For several problems some of the selected subspaces may lack the discriminant ability to separate the different classes. These subspaces produce poor classifiers that harm the performance of the ensemble. Additionally, boosting RSM would also be an interesting approach for improving its performance. Nevertheless, the application of the two methods together, boosting and RSM, achieves poor results, worse than the results of each method separately. In this work, we propose a new approach for combining RSM and boosting. Instead of obtaining random subspaces, we search subspaces that optimize the weighted classification error given by the boosting algorithm, and then the new classifier added to the ensemble is trained using the obtained subspace. An additional advantage of the proposed methodology is that it can be used with any classifier, including those, such as k nearest neighbor classifiers, that cannot use boosting methods easily. The proposed approach is compared with standard ADABoost and RSM showing an improved performance on a large set of 45 problems from the UCI Machine Learning Repository. An additional study of the effect of noise on the labels of the training instances shows that the less aggressive versions of the proposed methodology are more robust than ADABoost in the presence of noise.
10.1016/j.neunet.2007.12.046
pubmed_156_14052
OBJECTIVE To assess the effect of recombinant growth hormone (rhGH) therapy for liver cirrhosis patients with hypoproteinemia. METHODS Fifteen patients with liver cirrhosis were treated with rhGH (4 U per day) for 7 days and 15 controls were given human albumin (10 g) for every other day (altogether 3 times). Albumin was measured one day before the treatment, and on day 1, 10, 14, and 28 after the treatment. RESULTS After 7 days of rhGH administration, the albumin level of the patients was significantly higher and the function lasted longer than those of patients treated with human albumin (P < 0.05). CONCLUSION Exogenous rhGH in treating hypoproteinemia in patients with liver cirrhosis is more effective than human albumin.
pubmed_156_14052
pubmed_885_15213
PURPOSE To evaluate the relative enhancement of liver, pancreas, focal nodular hyperplasia (FNH), pancreas-to-liver index, and FNH-to-liver index in the hepatic arterial dominant phase (HADP) after injection of hepatocyte-specific MRI contrast agents, gadoxetic acid and gadobenate dimeglumine, on 3 and 1.5 Tesla (T) MRI in the same patient. MATERIALS AND METHODS The MRI database was retrospectively searched to identify consecutive patients who underwent abdominal MRI at 3T and 1.5T systems, using both 0.025 mmol/kg gadoxetic acid-enhanced and 0.05 mmol/kg gadobenate dimeglumine-enhanced MRI at the same magnetic strength field system. 22 patients were identified, 10 were scanned at 3T system and 12 at 1.5T system. The enhancement of liver, pancreas, and FNH was evaluated quantitatively on MR images. RESULTS The relative enhancement of liver in HADP in the gadobenate dimeglumine-enhanced group in all subjects was significantly higher than that in gadoxetic acid-enhanced group (P = 0.023). The gadobenate dimeglumine-enhanced group in HADP had better relative enhancement of pancreas and FNH, pancreas-to-liver index, and FNH-to-liver index than gadoxetic acid-enhanced group, but the difference was not statistically significant. CONCLUSION The 0.05 mmol/kg gadobenate dimeglumine-enhanced abdominal MRI studies at 3T and 1.5T MR systems are superior in relative enhancement of the liver in HADP to 0.025 mmol/kg gadoxetic acid-enhanced MRI. This type of assessment may provide comparative effectiveness data.
10.1002/jmri.23874
pubmed_857_17268
The bone mineral content of young adults as well as of osteoporotic patients and age-matched controls without bone disease was measured by single-photon absorptiometry. A retrospective nutrition survey was additionally made to study the relationship between bone mineral content and calcium intake in different periods of life. The bone mineral content and bone mineral density of young adults is directly related to the calcium intake through milk and dairy products. The osteoporotics had a significantly lower bone mineral content than the controls. Calcium intake through milk and milk products in childhood and adolescence had been significantly lower in the patients than in the controls, whereas in the later periods of life (20-30 years prior to the study and at the time of the study) there were no significant differences between the calcium intakes of the two groups. It was also found that an adequate intake of calcium protected against increased bone resorption, as evidenced in particular by the reduced levels of serum osteocalcin, a parameter of bone turnover. In conclusion it can be stated that the data support the hypothesis that adequate calcium intake through milk and milk products in childhood and adolescence is a decisive marker for obtaining a maximum bone mass (peak adult bone mass) and for the prevention of osteoporosis. Furthermore, it can be stated that increased calcium intake in the later years may not reduce the accelerated risk of osteoporosis resulting from inadequate calcium intake during childhood and adolescence.
pubmed_857_17268
pubmed_561_11170
The addition of L-alanine reduced lactate dehydrogenase leakage from primary cultured rat hepatocytes treated with galactosamine (D-gal), while D-alanine and other amino acids did not. However, the mechanisms have not yet been entirely clarified. In this study, we used various inhibitors of metabolism, i.e., aminooxyacetate, oligomycin, and quinolinic acid, to examine the relation between this protective effect and the metabolism of L-alanine. Quinolinic acid (10 mM) did not affect the hepatoprotective effect of L-alanine, while oligomycin (0.1 mug/ml) and aminooxyacetate (1 mM) eliminated the hepatoprotective effect of L-alanine. L-Alanine also increased the albumin secretion by cultured hepatocytes treated with D-gal, while pyruvate had little effect. It was revealed that the intracellular content of pyruvate did not increase as a result of addition of L-alanine. These results are consistent with the hypothesis that L-alanine metabolism is important for hepatoprotection, but pyruvate cannot be used as a substitute for L-alanine.
10.1006/bbrc.2002.6508
pubmed_766_3380
1. Complete crown epoxy resin dies are undersized. 2. MOD onlay epoxy resin dies are accurate. 3. Detail duplication of epoxy resin dies is comparable to that of die stone. 4. Hardness values of epoxy resin are generally less than those of die stone. The hardness of Epoxydent closely approached that of die stone.
10.1016/0022-3913(80)90045-1
pubmed_1029_9903
Magnesium and trace element determinations in 29 urinary tract calculi were carried out using an atomic absorption spectrophotometric method. Of the calculi examined, 9 were pure calcium oxalate, 5 were mixed calcium oxalate/uric acid, 5 were mixed calcium oxalate/phosphate, 5 were magnesium ammonium phosphate and 5 were pure cystine. The measurement of magnesium and trace element levels has been considered useful in the elucidation of the mechanism of stone formation and the evaluation of factors leading to pathological consequences. In this study, the Mg, Zn, Cu, Fe, Cd and Pb content in all of the samples was determined and an attempt was made to compare the levels of these elements in calculi with the levels in normal hair.
10.1111/j.1464-410x.1988.tb04318.x
pubmed_556_12340
Cytokinins (CKs) are adenine-derived, small-molecule plant growth regulators that control aspects of almost all plant growth and development processes. Internally, CKs play significant roles in plant cell division, nutrient allocation, and photosynthetic performance, and they are also detection and signaling agents for plant responses to the environmental challenges. CK functions in plant metabolism include plant adaptations to various abiotic stresses as well as their regulatory role in plant interactions with biotic components of the environment. Interestingly, CK biosynthesis is not exclusive to plants. New genetic and chemical approaches have revealed that both beneficial (symbiotic microorganisms) and detrimental (pathogenic bacteria, fungi, or insects) non-plant biota can secrete these phytohormones to purposefully modify plant metabolism. Therefore, while many open questions remain about how CKs are actively utilized by plants and plant-interacting organisms, CK roles should be seen more broadly, as signaling molecules for which effects range from within cells to as far as interkingdom relationships. The papers in this Special Issue highlight several aspects of CK biosynthesis, metabolism, and functions within plants and among plant-associated organisms, typifying the extensive range of roles played by these signaling molecules. The collection of papers represents new examples for CK researchers to consider advancing the growing range of topics related to how CKs mediate responses to many kinds of environmental stimuli and stresses.
10.3390/plants9091158
pubmed_639_24074
Skeletal trauma accounts for 10% to 15% of all childhood injuries, with approximately 15% to 30% of these representing physeal injuries. Talus fractures are rare injuries in children with an estimated prevalence of 0.008% of all childhood fractures. Cast immobilization is sufficient treatment for non-displaced fractures, however displaced fractures of the talus require surgical intervention to minimize the risk of trauma-related avascular necrosis (AVN) due to disruption of the vascular supply originating from the talar neck. A 13-year-old boy was brought to the accident and emergency (A/E) department following a road traffic accident while he was pillion riding a bike. Following the accident, he was unable to bear weight on his right foot and his anterior ankle region was swollen, with no neurological deficit or open wound. He had no other injury and no medical or surgical history. On review of the ankle and foot radiographs, he was noted to have a right talar neck fracture with subtalar and ankle dislocation. His computer tomographic (CT) images demonstrated a Hawkins Type IV talus fracture. Initial treatment involved a plaster of Paris (POP) back slab with the ankle in a neutral position. His right leg was elevated on pillows and treated with elevation and ice to alleviate the swelling. As the fracture was comminuted and displaced with ankle and subtalar dislocation, operative intervention (open reduction and fixation of talus with crossed K wires) was planned. The patient was discharged in below knee slab which was changed to a non-walking cast at two weeks. The patient was kept non-weight bearing until fracture united. These types of fractures are rare in children and proper clinical and radiological evaluation is essential. Such fractures should be reduced as early as possible to reduce the ischemia time thus prevent the chances of osteonecrosis. Lastly avoid tourniquets and stable anatomical reduction of fracture is must.
10.7759/cureus.13801
pubmed_490_19209
During the last 10 years, there have been major technological achievements in pediatric interventional cardiology. In addition, there have been several advances in cardiac imaging, especially in 3-dimensional imaging of echocardiography, computed tomography, magnetic resonance imaging, and cineangiography. Therefore, more types of congenital heart diseases can be treated in the cardiac catheter laboratory today than ever before. Furthermore, lesions previously considered resistant to interventional therapies can now be managed with high success rates. The hybrid approach has enabled the overcoming of limitations inherent to percutaneous access, expanding the application of endovascular therapies as adjunct to surgical interventions to improve patient outcomes and minimize invasiveness. Percutaneous pulmonary valve implantation has become a successful alternative therapy. However, most of the current recommendations about pediatric cardiac interventions (including class I recommendations) refer to off-label use of devices, because it is difficult to study the safety and efficacy of catheterization and transcatheter therapy in pediatric cardiac patients. This difficulty arises from the challenge of identifying a control population and the relatively small number of pediatric patients with congenital heart disease. Nevertheless, the pediatric interventional cardiology community has continued to develop less invasive solutions for congenital heart defects to minimize the need for open heart surgery and optimize overall outcomes. In this review, various interventional procedures in patients with congenital heart disease are explored.
10.3345/kjp.2017.60.8.237
pubmed_777_346
The possibility of controlling the harmful intra-articular influence of elevated interleukin (IL)-1beta synovial fluid concentration after anterior cruciate ligament (ACL) surgery could be useful. We investigated the correlation between serum and synovial fluid IL-1beta levels following ACL reconstruction. We measured IL-1beta concentration periodically in three synovial fluid and four serum samples in each of 20 patients receiving either autologous conditioned serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and several growth factors (group A) or placebo (group B). A decrease in IL-1beta synovial fluid concentration appeared to be more pronounced in absolute terms in group A. In eight patients serum IL-1beta was detected on the 6th postoperative day. In four of them whose synovial fluid levels were over 10 pg/ml on the 6th postoperative day, serum IL-1beta was detected on the 10th postoperative day. The results were different in group B. Correlation between serum and synovial fluid IL-1beta appearance persists in patients after ACL surgery and ACS application. This study is an example of ACS influence on the ACL healing process controlling the IL-1beta levels on the basis of the serum IL-1beta detection.
10.1007/s00264-008-0649-1
pubmed_944_23890
Efficient nutrient removal in decentralized wastewater treatment systems is a challenging task. To improve the removal of organic matter and nitrogen from wastewater, two types of bioreactors using membrane-aerated biofilm reactor (MABR) and microbial fuel cell (MFC) techniques were evaluated. During more than 250 days of continuous-flow reactor operation, both reactors showed consistently high chemical oxygen demand removal (>86%). At an influent ammonium-nitrogen (NH4(+)-N) concentration of 30 mg N/L, the average effluent NH4(+)-N concentrations were 6.2 and 0.5 mg N/L for the MABR and MFC reactor, respectively, while the effluent nitrate-nitrogen (NO3(-)-N) concentrations were 5.4 mg/ L in the MABR and 19.2 mg/L in the MFC-based reactor. The overall total inorganic nitrogen removal efficiencies were 64% and 36% for the MABR and MFC reactor, respectively. At the measured dissolved oxygen concentrations of 5.2 and 0.23 mg/L in the aerobic/anoxic zone of the MFC and MABR, respectively, a specific oxygen uptake rate of 0.1 g O2/g VSS-d, resulting from ammonia oxidation, was detected in the settled sludge of the MFC, while no nitrifying activity of the sludge from the MABR was detected. Molecular microbial analysis demonstrated a link between the bacterial community structure and nitrifying activity. The relatively high abundance of Nitrosomonas europaea was associated with its detectable nitrification activity in the settled sludge of the MFC. The results suggest that MABR and MFC techniques have the potential to improve organic and nitrogen removal in decentralized wastewater systems.
10.2175/106143011x12928814444691
pubmed_825_16682
RNA sequencing has been used to assess the relationships among species of the subgenus Sophophora of the genus Drosophila. Two divergent domains, D1 and D2, of the large ribosomal RNA (28S), totalling 550 nucleotides have been sequenced using the rRNA direct sequencing method. A tree has been reconstructed from the neighbor-joining algorithm and the confidence intervals were evaluated by the bootstrap procedure. Results have shown that the branching of the willistoni and saltans groups of the subgenus Sophophora is very ancient and probably predates that of the subgenus Drosophila. The other groups and subgroups of Sophophora are clustered in three main lineages: 1) the melanogaster and oriental subgroups; 2) the montium subgroup; 3) the ananassae subgroup of the melanogaster group clustered with the fima and obscura groups. Thus, in comparison with our results, several taxa of various ranks appear paraphyletic (the genus Drosophila, the subgenus Sophophora and the melanogaster group). Our biochemical phylogeny is only in partial agreement with the pattern of Throckmorton's radiations as well as with classical taxonomy, both based on morphological data.
10.1007/BF00116547
pubmed_921_604
Stridor in infants is a symptom that indicates partial obstruction of the large airways. Vascular rings are an unusual cause of tracheal compression which can induce stridor in infants and children. We report a 4-month-old boy with recurrent wheezing and stridor for 2 months. Spiral computed tomography (CT) and three-dimensional (3D) reconstruction aided in the diagnosis of external compression on the trachea by an innominate artery. Successful relief of the airway's obstruction was achieved by aortopexy. Three months after surgery, he was symptom free without any medication.
pubmed_921_604
pubmed_946_4383
The allograft of chicken spleen to homologous embryo recipients aged 9 days induces a systemic Graft Versus Host Reaction. In the 8 days after grafting, the recipients show a mesenchymatous goitre. The severity of the immunological conflict, expressed with the spleen index, and the decrease of thyroid activity, detected by follicle number reduction and T4 level fall, are closely linked; these findings indicate that, in this model, thyroid is a target organ of the immunological conflict.
pubmed_946_4383
pubmed_67_12190
Background: In the previous study, Puerariae Lobatae Radix (named Gegen in Chinese) water extract attenuated M3 receptor agonist carbachol-induced detrusor contraction after 3-week oral administration in a hypertension-associated OAB (overactive bladder) model. This research aimed to investigate the active ingredients from Gegen water extract against OAB. Methods: Bioassay-guided fractionation was performed by using preparative HPLC for fast isolation of fractions followed by screening their ex vivo activity through carbachol-induced bladder strip contraction assay. Chemicals in each active fraction were analyzed by HPLC-UV. Urine metabolites were quantified by LC-MS/MS after sub-acute administration. Thermal shift assay with the recombinant human M3 receptor protein was performed, and molecular docking analysis was used for molecular modelling of M3 receptor inhibition. Results: Bioassay-guided fractionation results for isolating M3 receptor inhibitors indicated that four compounds were identified as active ingredients of Gegen water extract, and their inhibition potency on carbachol-induced detrusor contraction was ranked in descending order according to their inhibition concentrations as follows: genistein > daidzein > biochanin A >> puerarin. Daidzein in urine reached an ex vivo effective concentration to inhibit detrusor contraction, but others did not. Daidzein concentration-dependently increased the melt temperature (Tm) of recombinant human M3 receptor protein with a positive binding (ΔTm = 2.12 °C at 100 μg/ml). Molecular docking analysis showed that daidzein can potently bind to the ligand binding pocket of the M3 receptor via hydrogen bonding. Conclusion: Puerarin and its derivatives were pro-drugs, and daidzein was their in vivo active form via M3 receptor inhibition for treating OAB.
10.3389/fphar.2022.924251
pubmed_723_24537
Dobutamine (DBT) is a sympathomimetic amine drug that was designed as an inotropic agent for use in congestive heart failure. Hence, there was an impetus to develop a rapid and accurate method for monitoring the concentration of DBT within clinical samples. To address this critical need, a novel In2O3 and functionalized multi-walled carbon nanotubes nanocomposite (In2O3@FMWCNTs) was successfully prepared and applied in an electrochemical sensor to detect DBT. The resulting sensor displayed electrocatalytic toward the oxidation of DBT, which attributed to the synergistic effect of In2O3 and FMWCNTs. Electrochemical impedance spectroscopy (EIS) studies revealed that the smaller charge transfer resistance value (Rct) was observed at In2O3@FMWCNTs modified glassy carbon spherical (GCS) paste electrode (PE) as compared to that of In2O3NPs/GCSPE, FMWCNTs/GCSPE and GCSPE, which authenticates its good conductivity. Furthermore, the calculated value of standard rate constant (ks) for the modified electrode demonstrates the fast electron transfer between DBT and the electrode surface. The fabricated electrochemical sensor indicated high selectivity and sensitivity for DBT determination over the oxidation of uric acid and ascorbic acid. The limit of detection of DBT at In2O3@FMWCNTs/GCSPE was found to be 1.42 × 10-10 M. The proposed sensor is effectively used for the detection of DBT in biological fluids, clinical patient blood and in injection dosage form.
10.1016/j.talanta.2019.120362
pubmed_970_3603
INTRODUCTION Enolases are enzymes in the glycolytic pathway, which catalyse the reversible conversion of D-2-phosphoglycerate into phosphoenol pyruvate in the second half of the pathway. In this research, the effects of α-enolase (ENO1) on steroid reproductive-related hormone receptor expression and on hormone synthesis of primary granulosa cells from goose F1 follicles were studied. MATERIAL AND METHODS Primary granulosa cells from the F1 follicles of eight healthy 8-month-old Zi geese were separated and cultured. An ENO1 interference expression vector was designed, constructed and transfected into primary cultured granulosa cells. The mRNA expression levels of follicle-stimulating hormone receptor (FSHR), luteinising hormone receptor (LHR), oestrogen receptor α (ER α), oestrogen receptor β (ER β), growth hormone receptor (GHR) and insulin-like growth factor binding protein-1 (IGFBP-1) in the cells were evaluated as were the secretion levels of oestradiol, activin, progesterone, testosterone, inhibin and follistatin in cell supernatant. RESULTS α-enolase gene silencing reduced the expression of FSHR, LHR, ERα, ERβ, GHR, and IGFBP-1 mRNA, potentiated the secretion of oestrogen, progesterone, testosterone, and follistatin of granulosa cells, and hampered the production of activin and inhibin. CONCLUSION ENO1 can regulate the reactivity of granulosa cells to reproductive hormones and regulate cell growth and development by adjusting their hormone secretion and reproductive hormone receptor expression. The study provided a better understanding of the functional action of ENO1 in the processes of goose ovary development and egg laying.
10.2478/jvetres-2020-0008
pubmed_695_21797
An expeditious route to planar chiral sulfur-based scaffolds has been achieved in two operational steps from cheap and commercial [2.2]paracyclophane hydrocarbon. The sulfur atom was introduced in a specific benzylic position of the [2.2]paracyclophane according to a reductive sulfanylation reaction, which proceeds under two complementary reaction conditions with either the BF3·OEt2/Et3SiH or TFA/BH3·THF combinations. The study was completed by the development of a highly efficient resolution approach by HPLC.
10.1021/acs.joc.0c02235
pubmed_449_4676
The present study investigated the correlation between cancer pain severity and mood states, and addressed methodological issues involved in measuring the association between these groups of variables. Five monthly interviews were administered to 95 cancer pain patients; each interview contained four measures of pain severity and the Profile of Mood States (POMS). The relationships between the two sets of variables were assessed using both interindividual (cross-sectional) and intraindividual (within-subject) methods of correlational analysis. Both types of analyses suggested small but significant positive correlations between the pain measures and negative mood states, and inverse correlations between pain and positive mood. The data also indicated that patients reported high levels of pain but reported little mood disturbance. In addressing methodological issues, the study clarified conceptual and computational differences between the two types of correlational analyses and indicated the appropriate applications of each method.
10.1007/BF00846327
pubmed_270_13166
We studied the aerobic bacterial isolates from bile and their susceptibilty pattern in patients with biliary tract disease. Samples of bile collected during endoscopic retrograde cholangio pancreatography (ERCP) and surgery, were inoculated on standard media. Bacterial identification and susceptibility were done by standard techniques. A total of 209 samples were cultured, out of which 128 samples showed growth. Total number of isolates obtained was 221. Poly-microbial infection was detected in 67 patients. Predominant aerobic bacterial isolates obtained were Escherichia coli 30% (67), Klebsiella species 23.98% (53), Enterococcus species 12.21% (27). Multi-drug resistance was noted in 57%. Higher resistance rate was noted among Gram negative bacilli for ampicillin (92.4%), cephalexin (82.46%), ciprofloxacin (68.42%), piperacillin (64.33%). Sensitivity to meropenem was 90.64% and amikacin was 76.61%. Gram positive bacteria showed high resistance to gentamicin (39.53%). Sensitivity to ampicillin was 86.05% and penicillin was 81.4%. Vancomycin and teicoplanin showed 100% sensitivity. From our study we conclude that E. coli, Klebsiella species and Enterococcus species are common pathogens infecting biliary tract. Poly-microbial infection and multi-drug resistance warrants culture and sensitivity to guide antimicrobial therapy. We recommend combination of amikacin and ampicillin for empirical therapy at our institution.
pubmed_270_13166
pubmed_656_1847
Long noncoding RNAs (lncRNAs) play important roles in regulating diverse cellular processes in the vessel wall, including atherosclerosis. RNA-Seq profiling of intimal lesions revealed a lncRNA, VINAS (Vascular INflammation and Atherosclerosis lncRNA Sequence), that is enriched in the aortic intima and regulates vascular inflammation. Aortic intimal expression of VINAS fell with atherosclerotic progression and rose with regression. VINAS knockdown reduced atherosclerotic lesion formation by 55% in LDL receptor-deficient (LDLR-/-) mice, independent of effects on circulating lipids, by decreasing inflammation in the vessel wall. Loss- and gain-of-function studies in vitro demonstrated that VINAS serves as a critical regulator of inflammation by modulating NF-κB and MAPK signaling pathways. VINAS knockdown decreased the expression of key inflammatory markers, such as MCP-1, TNF-α, IL-1β, and COX-2, in endothelial cells (ECs), vascular smooth muscle cells, and bone marrow-derived macrophages. Moreover, VINAS silencing decreased expression of leukocyte adhesion molecules VCAM-1, E-selectin, and ICAM-1 and reduced monocyte adhesion to ECs. DEP domain containing 4 (DEPDC4), an evolutionary conserved human ortholog of VINAS with approximately 74% homology, showed similar regulation in human and pig atherosclerotic specimens. DEPDC4 knockdown replicated antiinflammatory effects of VINAS in human ECs. These findings reveal a potentially novel lncRNA that regulates vascular inflammation, with broad implications for vascular diseases.
pubmed_656_1847
pubmed_402_9279
The increasing use of CT for the evaluation of blunt abdominal trauma has diagnosed undetected pneumothoraces in many patients. We performed a retrospective study at a major trauma center to determine the incidence of occult pneumothorax in the trauma patient. All trauma patients (3121) admitted to a Level I trauma center over a 51-month period were reviewed to determine the incidence of pneumothorax and occult pneumothorax, the method of diagnosis, and treatment. All major trauma patients received a chest X-ray (CXR), whereas 842 patients (27%) underwent an abdominal CT scan. In the 172 patients diagnosed with pneumothorax, 157 abdominal CT scans were performed and 143 were positive for pneumothorax. CXR revealed 49 right-sided pneumothoraces and 58 left-sided pneumothoraces in 95 patients. Abdominal CT scans diagnosed 73 right pneumothoraces and 90 left pneumothoraces in 143 patients. There were 67 patients (71 thoraces) who were seen to have a pneumothorax on abdominal CT scan not seen on admission CXR. This represents 2.2 per cent of all trauma patients and 7.9 per cent of patients with abdominal CT scans. In looking at just trauma patients with pneumothorax, the CT scan was responsible for diagnosing 39 per cent of the patients with a pneumothorax. The occult pneumothorax is being diagnosed more frequently as methods of evaluating and diagnosing trauma patients become more sensitive.
pubmed_402_9279
pubmed_279_21817
Isolated hepatocytes from obese Zucker rats showed an increased capacity for lipid synthesis measured as the incorporation of 3H2O into lipid fractions. In addition lipid synthesis from 1 mM U-14C-alanine was elevated as compared to those isolated from their lean counterparts. On these lines, the amino acid was a better lipogenic substrate than U-14C-lactate at 5 mM concentration. Insulin increased lipid synthesis from the amino acid in the lean animals while showed no effects on this parameter in the obese. While the hepatocytes from the lean animals used to a similar extent U-14C-alanine carbon from 14CO2 production, lipid synthesis and 14C-glycogen incorporation, those from the obese animals showed a decreased oxidation and glycogen incorporation while an augmented lipid synthesis. The total amount of the amino acid taken up by the obese animals was also significantly elevated. Conversely, the metabolic fate of U-14C-leucine was very similar between the two groups. It can be concluded that in the obese Zucker rat alanine is a very important amino acid which contributes to sustain the high liver hyperlipogenesis previously described.
pubmed_279_21817
pubmed_536_8141
Parameters of the Jacobi room model were estimated with simulation of Brownian motion. Deposition on internal room surfaces and attachment of progeny atoms to three modally distributed aerosols were taken into account. The values of parameters were presented as functions of aerosol concentrations. The deposition rate of an unattached progeny was estimated in the range 30-47 h-1; the deposition rate of an attached progeny was very small and its range is 0.0007-0.004 h-1; the attachment rate of a progeny is in range 40-170 h-1. The statistical uncertainty was lower than 1%. The ranges of parameters were similar to those reported in literature.
10.1097/01.HP.0000326328.47540.6d
pubmed_38_21703
How does attention alter neural responses? Decades of electrophysiological measurements in non-human primates as well as human EEG and fMRI studies have shown that spatial attention modulates firing rates across the visual cortex, but the computations that drive this process are still unclear. Further, while it is well known that attention affects perception, we have only a limited understanding of the link between attentionally driven changes in neural firing rates and subject performance. Here we used a novel human neuroimaging method to measure the effect of spatial attention on neural responses in V1, hMT+, hV4, and the intraparietal sulcus (IPS). Attention altered signals in different ways across the visual cortex: areas V1, hMT+, and IPS exhibited primarily response gain changes while hV4 showed contrast gain modulation. Signals in V1, hMT+, and IPS correlated with contrast detection performance suggesting that behavior can be predicted by population-level signals as early as striate cortex.
pubmed_38_21703
pubmed_637_9455
INTRODUCTION Congenital Heart Defects (CHDs) are one of the most common forms of congenital anomalies. Fetal echocardiography performed during second trimester aims at early diagnosis of congenital heart disease which is instrumental in proper planning of delivery, perinatal care and counselling of parents. AIM To evaluate the role of fetal echocardiography in prenatal screening of CHDs and to study the role of associated extracardiac anomalies. MATERIALS AND METHODS This was a hospital based prospective and correlative type of study, done over a period of one year. Antenatal screening of fetal heart was done in mid-trimester high and low risk pregnancies. The prenatal echo findings were co-related with postnatal findings in case of any abnormality detected. The extra-cardiac anomalies associated with positive cases were evaluated and studied for their impact on postnatal outcome. RESULTS A total of 1200 pregnancies were screened out of which 672 were low risk and 528 were high risk. The cases with abnormal echo findings were followed postnatally. The overall incidence of CHD in study population was 15 per 1000. The incidence in high and low risk pregnancies were 16.3 and 13.25 per thousand respectively. Complete agreement of 68.17% was found between prenatal and postnatal findings. The most frequent Extra-Cardiac Anomalies (ECA) in cases with CHD was of musculoskeletal system. The CHD cases with ECA were significantly of low birth weight, born preterm and delivered by Lower Segment Caesarean Section (LSCS). CONCLUSION Fetal heart is the most overlooked part in every routine anomaly scan. We conclude that fetal echocardiography should be an integral part of every second trimester anomaly scan for all pregnant females irrespective of their risk factors. The associated ECAs are another factor that causes increased mortality both in antenatal and neonatal life, again warranting an early fetal echo.
10.7860/JCDR/2017/25929.9750
pubmed_1075_24932
Sequencing studies using whole-genome or exome scans are still more expensive than genome-wide association studies on a per-subject basis. As a result, only a subset of subjects from a larger study will be selected for sequencing. To perform an agnostic investigation of the entire genome, subjects may be selected that capture independent ancestral lineages, i.e., founder genomes, and thus avoid redundant information from regions that were inherited identical by descent (IBD) from a common ancestor. We present SampleSeq2 that can be used to select a subset of optimally unrelated subjects with minimal IBD sharing. It also can be used to estimate the number, G(T), of founder chromosomes in a sample or select the minimum number of subjects that will carry a target G(T). We evaluated SampleSeq2 compared to a random draw of a small number of subjects both by simulation and using the Anabaptist genealogy. SampleSeq2 provided an increase in G(T) relative to a random draw across a range of small sample sizes. This increase in founder chromosomes improves the power of association tests, mitigates the effect of cryptic relatedness on parameter estimates, increases the total yield of alleles from sequencing, and minimizes the average size of regions shared IBD around disease alleles in cases.
10.1002/gepi.21641
pubmed_202_17968
In previous work, we established that treatment with melphalan (L-phenylalanine mustard) produced a predominance of A.T-->T.A transversions in the Simian virus 40 (SV40)-based shuttle vector pZ189 during replication in human 293 cells. Mutations were induced with varying doses (4-12 microM) melphalan in the aprt gene of the hemizygous Chinese hamster ovary (CHO) cell line D422 to determine whether a similar mutation spectrum would be observed in an endogenous gene. DNA sequence alterations were determined for 39 spontaneous and 41 melphalan-induced independent mutant clones. Other than a predominance of transversions in both systems, the spectrum of melphalan-induced aprt mutations bears little resemblance to the spectrum observed in the supF gene of the shuttle plasmid pZ189. In aprt, mutations at G.C base pairs (bp) predominated (29 of 41 base substitutions). Significantly enhanced mutagenesis was observed at 5' G-G-C 3' and 5' G-G-C-C 3' sites in the aprt gene. Almost half of the melphalan-induced base substitutions occurred at 5' G-N-C 3' sequences, which are believed to be potential interstrand crosslink sites.
10.1016/0165-4608(92)90326-4
pubmed_674_25309
Hepatitis B virus (HBV) reverse transcriptase (RT) is encoded by the polymerase gene in the reverse transcriptase region, which overlaps with the S gene. The association between mutations of HBV RT and the pathobiological features of hepatocellular carcinoma (HCC) remain to be elucidated. The present study aimed to examine mutations in this region of the HBV genome and its clinical significance. Briefly, HBV total DNA was extracted from 84 pairs of HCC tumor tissue and corresponding adjacent non‑tumor tissue samples. The RT/S regions (nt130‑1161) were amplified and sequenced using the Sanger method, and associations between RT mutations and the clinical characteristics of patients with HCC were analyzed. Finally, 27 and 29 mutations with frequencies >5% were identified in the RT and S regions, respectively. The rtF221Y variation and a tumor size >8 cm were found to be independent risk factors for the postoperative recurrence of HCC, with hazard ratios of 2.345 (95% CI, 1.391‑3.953; P=0.001) and 1.838 (95% CI, 1.069‑3.161; P=0.028), respectively. rtF221Y was also an independent risk factor for poor overall survival rates (HR=2.557; 95% CI, 1.344‑4.866; P=0.004). The mutation of R122 K in the HBV S protein was closely associated with tumor recurrence (P<0.001). As a result, rtF221Y was identified as a risk factor for poor prognosis and may be a potential viral marker for predicting prognosis in HCC.
10.3892/mmr.2017.6362
pubmed_614_9684
Prior to transplantation, mesenchymal stem/stromal cells (MSCs) can be induced toward the osteoblastic phenotype using a cocktail of soluble supplements. However, there is little evidence of differentiated MSCs directly participating in bone formation, suggesting that MSCs may either die or revert in phenotype upon transplantation. Cell-secreted decellularized extracellular matrices (DMs) are a promising platform to confer bioactivity and direct cell fate through the presentation of a complex and physiologically relevant milieu. Therefore, we examined the capacity of biomimetic DMs to preserve the mineral-producing phenotype upon withdrawal of the induction stimulus. Regardless of induction duration, ranging up to 6 weeks, MSCs exhibited up to a 5-fold reduction in osteogenic markers within 24 h following stimulus withdrawal. We show that seeding osteogenically induced MSCs on DMs yields up to 2-fold more calcium deposition than tissue culture plastic, and this improvement is at least partially mediated by increasing actin cytoskeletal tension via the ROCK II pathway. MSCs on DMs also secreted 25% more vascular endothelial growth factor (VEGF), a crucial endogenous proangiogenic factor that is abrogated during MSC osteogenic differentiation. The deployment of DMs into a subcutaneous ectopic site enhanced the persistence of MSCs 5-fold, vessel density 3-fold, and bone formation 2-fold more than MSCs delivered without DMs. These results underscore the need for deploying MSCs using biomaterial platforms such as DMs to preserve the in vitro-acquired mineral-producing phenotype and accelerate the process of bone repair.
pubmed_614_9684
pubmed_1094_3217
Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content is a key determinant of its structure/function, thereby affecting ECT therapeutic potential for advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell sorting by using cardiac-specific markers. Notably, ECTs showed synchronized spontaneous beating when cardiomyocytes constituted ≥50% of total cells, with the electrical-conduction velocity increasing depending on cardiomyocyte ratio; however, ECTs containing 90% cardiomyocytes failed to form stable structures. ECTs containing 25% or 50% cardiomyocytes predominantly expressed collagen and fibronectin, whereas ECTs containing 70% cardiomyocytes predominantly expressed laminin and exhibited the highest contractile/relaxation properties. Furthermore, transplantation of ECTs containing 50% or 70% cardiomyocytes into a rat chronic myocardial infarction model led to a more profound functional recovery as compared with controls. Notably, transplanted ECTs showed electrical synchronization with the native heart under Langendorff perfusion. Collectively, these results indicate that the quantity of non-cardiomyocytes is critical in generating functional iPSC-derived ECTs as grafts for cardiac-regeneration therapy, with ECTs containing 50-70% cardiomyocytes exhibiting stable structures and increased cardiotherapeutic potential.
10.1089/ten.TEA.2016.0535
pubmed_360_5379
Food is mankind's most basic need. A recent global survey revealed that the single most important problem in the world--in developed and developing countries alike--was the high cost of living, and of food, its major component. In a world where many are starving, undernourished, malnourished or suffering from deficiency diseases, the problems of food quality and safety must be given special attention. Many developed countries have already made food a priority and created effective systems of consumer protection for food. But a number of developing countries are still struggling with the best way to control food problems. This paper will deal primarily with food and consumer protection problems in Asia and the Pacific region, but the solutions offered are universal.
pubmed_360_5379
pubmed_767_2354
Key genes involved in metabolism and signalling of abscisic acid and gibberellins during Epimedium pseudowushanense B.L.Guo seed morphophysiological dormancy release were identified using phytochemistry, transcriptomics, and bioinformatic methods. The molecular mechanism of seed morphophysiological dormancy of Epimedium pseudowushanense B.L.Guo. remains largely unknown. The endogenous abscisic acid (ABA) and gibberellin (GA) content of E. pseudowushanense seeds at three developmental stages were quantitatively determined. The results showed the levels of ABA in E. pseudowushanense seeds decreased during seed embryo growth and development, while levels of GA3 increased during seed embryo growth, and levels of GA4 increased during seed dormancy release and seed sprouting. A high-throughput sequencing method was used to determine the E. pseudowushanense seed transcriptome. The transcriptome data were assembled as 178,613 unigenes and the numbers of differentially expressed unigenes between the seed development stages were compared. Computer analysis of reference pathways revealed that 12 candidate genes were likely to be involved in metabolism and signalling of ABA and GAs. The expression patterns of these genes were revealed by real-time quantitative PCR. Phylogenetic relationships among the deduced E. pseudowushanense proteins and their homologous proteins in other plant species were analysed. The results indicated that EpNCED1, EpNCED2, EpCYP707A1, and EpCYP707A2 are likely to be involved in ABA biosynthesis and catabolism. EpSnRK2 is likely implicated in ABA signalling during seed dormancy. EpGA3ox is likely to be involved in GA biosynthesis. EpDELLA1 and EpDELLA2 are likely implicated in GA signalling. This study is the first to provide the E. pseudowushanense seed transcriptome and the key genes involved in metabolism and signalling of ABA and GAs, and it is valuable for studies on the mechanism of seed morphophysiological dormancy.
10.1007/s00299-018-2291-8
pubmed_936_5329
Heat perception enables acute avoidance responses to prevent tissue damage and maintain body thermal homeostasis. Unlike other modalities, how heat signals are processed in the spinal cord remains unclear. By single-cell gene profiling, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat-sensitive spinal neurons in mice. Ablating spinal ErbB4+ neurons attenuates heat sensation. These neurons receive monosynaptic inputs from TRPV1+ nociceptors and form excitatory synapses onto target neurons. Activation of ErbB4+ neurons enhances the heat response, while inhibition reduces the heat response. We showed that heat sensation is regulated by NRG1, an activator of ErbB4, and it involves dynamic activity of the tyrosine kinase that promotes glutamatergic transmission. Evidence indicates that the NRG1-ErbB4 signaling is also engaged in hypersensitivity of pathological pain. Together, these results identify a spinal neuron connection consisting of ErbB4+ neurons for heat sensation and reveal a regulatory mechanism by the NRG1-ErbB4 signaling.
10.1016/j.neuron.2022.04.021
pubmed_167_22518
Daily dynamics of changes in the latency of a response to dissociative anesthetic tiletamine (time from injection to ataxia) was studied in mature Wistar rats. Both intramuscular and intravenous administration of the anesthetic was associated with 4-day oscillations of the latent period synchronous with the dynamics of changes in the concentration of glucocorticoid hormones. The period and phases of the infradian rhythm of resistance to the anesthetic remained unchanged after removal of both adrenal glands and testes and administration of corticosterone synthesis blocker trilostane diminishing the 4-day cycle of changes in corticosterone level. Therefore, hormones of the adrenal glands and testes do not play the key role in the mechanisms of formation of the 4-day infradian rhythm.
10.1007/s10517-019-04362-x
pubmed_163_11953
The Fontan is a complex surgical procedure used as a palliative treatment for children with univentricular hearts. In the past, the mortality rate was high and the associated comorbidities as a result of the Fontan circulation were many. However, as research into the condition developed, better understanding has led to a massive reduction in early mortality and a rapidly increasing population of such patients surviving well into adulthood. This has led to a large surge in patients with congenital heart disease being referred for cardiac transplant assessment. According to research, listing these patients at the optimal time is the key to improving transplant outcomes. However, determining that optimal time is unclear and controversial. In this article, I address this issue by developing an optimal timing rule that accounts for the factors faced by specialist cardiologists in determining when transplant ought to be considered for this cohort of patients.
10.1177/23814683211057472