Hypolipidemic and antioxidant effects of dietary curcumin and capsaicin in induced hypercholesterolemic rats.
Health beneficial hypolipidemic and antioxidant influences of dietary spice principles--curcumin, capsaicin alone and in combination included in the diet for 8 weeks were evaluated in induced hypercholesterolemic rats, in order to verify if there is any additive or synergistic effect of these two bioactive compounds. Dietary curcumin (0.2%), capsaicin (0.015%) or their combination significantly countered the hypercholesterolemia brought about by high cholesterol feeding. Hepatic cholesterol was lowered by dietary spice principles only in normal rats. Liver triglyceride levels were lowered in both normal and hypercholesterolemic rats by capsaicin. Curcumin and capsaicin lowered hepatic and blood lipid peroxides in hypercholesterolemic rats, while the effect in blood was additive with their combination. Hepatic ascorbic acid was enhanced by dietary spice principles in normal rats; glutathione was enhanced by their combination only in hypercholesterolemic rats. Activities of serum glutathione reductase, glutathione transferase and catalase and hepatic glutathione reductase in normal rats and serum glutathione peroxidase in hypercholesterolemic rats were enhanced by dietary spice principles. While dietary curcumin and capsaicin normalized the changes in the levels of antioxidant molecules and activities of antioxidant enzymes to a significant extent, this effect was not generally additive when given in combination, and was higher than the individual effects only in a few instances.


Characterisation of pSMA23, a 3.5 kbp plasmid of Lactobacillus casei, and application for heterologous expression in Lactobacillus.
The complete nucleotide sequence of plasmid pSMA23 isolated from Lactobacillus casei A23 was determined. Plasmid pSMA23 is a 3497bp circular molecule with a G+C content of 38.18%. Four putative open reading frames were identified. Based on homology, two orfs were identified as genes encoding replication initiation (Rep) and mobilisation (Mob) protein, respectively. Various regulatory regions like promoters, ribosome binding site (RBS), transcriptional terminators were deduced from the sequences of rep and mob. The origin of replication (dso) was predicted. Shuttle vectors pL142 and pL157 were constructed for Escherichia coli and Lactobacillus using rep gene and ori of pSMA23 for replication in Lactobacillus, the ori of the commercial vector pBluescript SkII+ for replication in E. coli, and the erythromycin and chloramphenicol resistance genes of pE194 and pC194, respectively, as selection markers. Transformants of E. coli and Lactobacillus were obtained on media containing erythromycin and chloramphenicol, respectively, suggesting expression of the ermC and cat194 genes in both organisms. The shsp gene of plasmid pSt04 of Streptococcus thermophilus encoding a small heat shock protein and the Lactobacillus plantarum cbh gene encoding conjugated bile salts hydrolase were cloned and successfully expressed in the heterologous host Lb. casei LK1 with the aid of pSMA23-derived vectors.


Quantitative proteomic analysis reveals complex regulatory and metabolic response of Iris lactea Pall. var. chinensis to cadmium toxicity.
Cadmium pollution has become a serious environmental problem. Iris lactea var. chinensis showed strong Cd tolerance and accumulation ability, which has significant potential to be applied for the phytoremediation of Cd-contaminated soil. However, the lack of molecular information on the mechanism of I. lactea response to Cd limited the improvement of phytoremediation efficiency. In this study, label-free proteomics analysis of Cd response in I. lactea showed that there were 163 and 196 differentially expressed proteins (DEPs) in the shoots and roots, respectively. Bioinformatics analysis indicated the DEPs responding to Cd stress mainly involved in signal transduction, ion transport, redox etc., and participate in the pathway of amino acid biosynthesis, lignin biosynthesis, glycerolipid metabolism and glutathione metabolism. Besides, differential expression of seven DEPs was validated via gene expression analysis. Finally, we found that a Cd-induced mannose-specific lectin (IlMSL) from I. lactea enhanced the Cd sensitivity and increased Cd accumulation in yeast. The results of this study will enhance our understanding of the molecular mechanism of Cd tolerance and accumulation in I. lactea and ultimately provide valuable resources for using Cd tolerant genes for developing efficient strategies for phytoremediation of Cd-contaminated soils or limiting Cd accumulation in food crops.


Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression.
The Wnt/beta-catenin signaling cascade is an important signal transduction pathway in human cancers. Overexpression of beta-catenin and its downstream effector, cyclin D1, is implicated in malignant transformation and acquisition of an invasive tumor phenotype. This study aimed to determine the clinical significance of Wnt/beta-catenin canonical pathway components in breast cancer. Expression of beta-catenin, dishevelled (Dvl) and cyclin D1 was examined in invasive ductal carcinomas (IDCs) of the breast by immunohistochemical analysis. Of the 98 IDCs analyzed, 30% of tumors displayed both nuclear and cytoplasmic staining of Dvl protein, while 52% showed nuclear localization. Loss of cell surface beta-catenin was observed in 66% of breast carcinomas, whereas nuclear expression was observed in 48% IDCs. Cyclin D1 overexpression was observed in 60% IDCs; 31/59 (53%) of these tumors showed nuclear expression of beta-catenin, suggesting upregulation of the canonical Wnt/beta-catenin pathway. Our study demonstrates a significant association between nuclear localization of Dvl and beta-catenin (p < 0.01, OR = 15.8). To our knowledge, this is the first study showing an association between nuclear localization of Dvl and beta-catenin in IDCs and suggests the upregulation of Wnt/beta-catenin pathway components, beta-catenin, Dvl and cyclin D1 in IDCs of the breast.


Durable lithium-ion insertion/extraction and migration behavior of LiF-encapsulated cobalt-free lithium-rich manganese-based layered oxide cathode.
Lithium-rich manganese-based cathode has made a subject of intense scrutiny for scientists and application researchers due to their exceptional thermal stability, high specific capacity, high operating voltage, and cost-effectiveness. However, the inclusion of cobalt, as a crucial component in lithium-rich manganese-based cathode materials, has become a cause for concern due to its limited availability and non-renewable nature, which eventually limits the growth of the battery industry and increase costs. Considering the poor stability of cobalt-free cathode, this work proposes a coating strategy of LiF through a simple high-temperature melting method. Directly coating LiF on Li1.2Ni0.2Mn0.6O2 surface is found to be an effective way to protect the cathode material, decrease metal solubility, and inhibit irreversible phase transition processes, thus leading to an improved electrochemical performance. As a result, the battery employing LiF coated Li1.2Ni0.2Mn0.6O2 cathode can be stabilized over 280 cycles and maintain a capacity of 110 mAh g-1 at 1C. What's more, the mechanisms of ion insertion/extraction behavior and ion migration process are also studied systematically. This study will open the avenue to develop a high-energy battery system with cobalt-free cathode.


To support the use of NT-proBNP to better detect heart failure in patients with type 2 diabetes.
Heart failure (HF) is a chronic disease that causes approximately 300,000 and 250,000 deaths per year in Europe and United States, respectively. Type 2 Diabetes Mellitus (T2DM) is one the major risk factors of HF, and the investigation of NT-proBNP might support the early identification of HF in T2DM sufferers. Nevertheless, this parameter is poorly investigated. Thus, we aimed to demographically and clinically characterize diabetic patients which were prescribed with NT-proBNP in the primary care setting. Using a primary care database, we formed a cohort of patients aged ≥18 years diagnosed with T2DM between 2002 and 2021. A multivariate Cox model was adopted to assess the determinants associated with the prescription of NT-proBNP. Among 167,961 T2DM patients, 7558 (4.5%, 95% CI: 4.4-4.6) were prescribed with NT-proBNP. Males and increasing age were expectedly associated with a higher propensity to be prescribed with NT-proBNP. In addition, a significant association was found for those suffering from obesity, ischemic cardiomyopathy, stroke, atrial fibrillation, hypertension, and with a Charlson Index of 2+. These determinants might contribute to investigate the NT-proBNP in T2DM sufferers. A decision support system to appropriately ease the prescription of NT-proBNP might be therefore implemented in primary care settings.


Life course socioeconomic disadvantage and cognitive function among the elderly population of seven capitals in Latin America and the Caribbean.
To examine the influence of life course socioeconomic disadvantages (SED) on cognitive function in later life. Data originate from a survey of people 60 and older living in seven Latin American and Caribbean cities. Cognitive function was measured with a modified Mini-Mental State Examination and the Pfeffer Scale of Functional Capacity. Homogeneity tests were used to pool data. Associations between cognitive function and SED were evaluated, fitting logistic regressions. Cognitive impairment (CI) prevalence ranged from 0.3% to 6.5% in men and 1.2% to 10.1% in women. Childhood rural living, poor childhood health, illiteracy, housewife or farmer occupation, and insufficient income were associated with CI in all seven cities. The odds of CI increase with cumulative exposure to disadvantages along life course. Life course SED is related to cognitive function later in life. Difficulty in properly distinguishing cognitive function from test performance remains an issue.


Sex differences in presentation and outcome among patients with type 2 diabetes and coronary artery disease treated with contemporary medical therapy with or without prompt revascularization: a report from the BARI 2D Trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes).
This study evaluated differences in outcome among women and men enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Women and men with coronary artery disease have different clinical presentations and outcomes that might be due to differences in management. We compared baseline variables, study interventions, and outcomes between women and men enrolled in the BARI 2D trial and randomized to aggressive medical therapy alone or aggressive medical therapy with prompt revascularization. At enrollment, women were more likely than men to have angina (67% vs. 58%, p < 0.01) despite less disease on angiography (Myocardial Jeopardy Index 41 ± 24 vs. 46 ± 24, p < 0.01; number of significant lesions 2.3 ± 1.7 vs. 2.8 ± 1.8, p < 0.01). Over 5 years, no sex differences were observed in BARI 2D study outcomes after adjustment for difference in baseline variables (death/myocardial infarction/cerebrovascular accident: hazard ratio: 1.11, 99% confidence interval [CI]: 0.85 to 1.44). However, women reported more angina than men (adjusted odds ratio: 1.51, 99% CI: 1.21 to 1.89, p < 0.0001) and had lower scores for the Duke Activity Status Index (adjusted beta coefficient: -1.58, 99% CI: -2.84 to -0.32, p < 0.01). There were no sex differences in death, myocardial infarction, or cerebrovascular accident among patients enrolled in the BARI 2D trial. However, compared with men, women had more symptoms and less anatomic disease at baseline, with persistence of higher angina rates and lower DASI scores after 5 years of medical therapy with or without prompt revascularization. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).


Sodium, added sugar and saturated fat intake in relation to mortality and CVD events in adults: Canadian National Nutrition Survey linked with vital statistics and health administrative databases.
This study aimed to determine whether higher intakes of Na, added sugars and saturated fat are prospectively associated with all-cause mortality and CVD incidence and mortality in a diverse population. The nationally representative Canadian Community Health Survey-Nutrition 2004 was linked with the Canadian Vital Statistics - Death Database and the Discharge Abstract Database (2004-2011). Outcomes were all-cause mortality and CVD incidence and mortality. There were 1722 mortality cases within 115 566 person-years of follow-up (median (interquartile range) of 7·48 (7·22-7·70) years). There was no statistically significant association between Na density or energy from saturated fat and all-cause mortality or CVD events for all models investigated. The association of usual percentage of energy from added sugars and all-cause mortality was significant in the base model with participants consuming 11·47 % of energy from added sugars having 1·34 (95 % CI 1·01, 1·77) times higher risk of all-cause mortality compared with those consuming 4·17 % of energy from added sugars. Overall, our results did not find statistically significant associations between the three nutrients and risk of all-cause mortality or CVD events at the population level in Canada. Large-scale linked national nutrition datasets may not have the discrimination to identify prospective impacts of nutrients on health measures.


Pulmonary manifestations of childhood-onset primary Sjogren's syndrome (SS) masquerading as reactive airways disease in a male patient and review of interstitial lung disease associated with SS.
Sjogren's syndrome (SS) is a rare chronic autoimmune disease involving exocrine glands presenting with sicca syndrome, recurrent parotitis and other extraglandular stigmata. SS is well characterized in the adult population with classification criteria; however, primary SS presenting in childhood is poorly defined and rare in males. Recurrent parotitis is the most common presenting symptom in children with primary SS; however, clinical phenotype in children appears more variable than in adults. The lungs are a common extraglandular location for manifestations of primary SS. However, interstitial lung disease (ILD) is rare in children with primary SS. There are only four published reports of ILD associated with primary SS in female children. Here, we present a very rare case of primary SS in a pediatric male with pulmonary manifestations and review of the literature on ILD in childhood-onset primary SS. A 14-year-old White male with a history of chronic severe asthma, recurrent parotitis and idiopathic intracranial hypertension was referred to pediatric rheumatology for evaluation of a positive ANA. In early childhood, he was diagnosed with persistent asthma recalcitrant to therapy. At age 8, he developed recurrent episodes of bilateral parotitis despite multiple treatments with sialoendoscopy. At age 14, respiratory symptoms significantly worsened prompting reevaluation. Lab workup was notable for positive ANA and Sjogren's Syndrome A and B antibodies. Pulmonary function tests showed only a mild obstructive process. Computed tomography of chest was significant for small airway disease, and lung biopsy was positive for mild interstitial lymphocytic inflammation presenting a conflicting picture for ILD. The constellation of findings led to the diagnosis of primary SS with associated pulmonary manifestations. He was treated with hydroxychloroquine, mycophenolate mofetil and oral corticosteroids with resolution of symptoms. Primary SS is a rare disease in the pediatric population that is poorly characterized. This case is the very rare presentation of childhood-onset primary SS with pulmonary manifestations in a male patient. ILD associated with primary SS is also very rare with only four pediatric patients reported in the literature. Collaborative effort is needed to develop pediatric specific diagnostic and treatment guidelines in this rare condition.


Discrimination of toxigenic and non-toxigenic Aspergillus flavus in wheat based on nanocomposite colorimetric sensor array.
A novel method was developed for the early detection of wheat infected with Aspergillus flavus (A. flavus) using a nanocomposite colorimetric sensors array (CSA). LC-MS analysis revealed the presence of Aflatoxin B1 (AFB1) and Aflatoxin B2 (AFB2) on day seven, demonstrating mycotoxin variabilities in infected wheat. HS-SPME-GC-MS analysis detected 2-methylbutyral, a gas exclusively associated with toxigenic A. flavus. The CSA was modified using three nanoparticles of MOF and successfully used to detect the wheat infected with A. flavus. Discrimination of different types of infected wheat samples was achieved using the RGB difference map and Principal Component Analysis (PCA) model. Additionally, the Linear Discriminant Analysis (LDA) model accurately predicted the presence of toxigenic A. flavus at various stages of infection. These findings highlight the promising capabilities of nanocomposite CSA for early-stage detection of A. flavus infection in wheat.


Low-fat school lunch programs: achieving acceptance.
A study was carried out to determine whether hands-on classroom experience with low-fat foods would increase children's acceptance of those foods in the school's lunch program. The 9-month project took place at an elementary school in upstate New York. Half of the classrooms served as the intervention group and received classroom experience with new foods; the other half served as the control group and received no classroom experience. Consumption measurements of 16 new foods, introduced at approximately 2-week intervals, were taken for all students who ate school lunches. Compared with children in the control group, those in the intervention group ate significantly more of the new foods when they were offered in the lunch program. The study demonstrated that experiential learning about food in the classroom is an effective way to gain acceptance of diverse, low-fat foods in the school lunch program.


Laparoscopy in infants and children.
Laparoscopy has been performed in 60 infants and children over a 32-mo period. Indications included: the problem of possible appendicitis, chronic abdominal pain, possible regional enteritis, possible biliary atresia, and liver biopsy. Fifty-two per cent of patients were spared laparotomy, while in 32% the need for operation was established. There were 2 errors in diagnosis, 3 failures, and 1 complication. Laparoscopy is considered to be a safe, effective, and economical diagnostic procedure that deserves wider application in the pediatric patient.


Indisulam exerts anticancer effects via modulation of transcription, translation and alternative splicing on human cervical cancer cells.
Indisulam is a synthetic sulfonamides drug with anticancer activity in various tumors. However, the effect and molecular mechanism of indisulam have still not been studied in human cervical cancer. We treated human cervical cancer cell lines (HeLa and C33A) with indisulam, evaluated its efficacy, and investigated its molecular targets. Indisulam inhibited tumor growth and induced RBM39 degradation in a dose-dependent manner. RNA-seq and proteomics analysis revealed that indisulam disrupted transcriptional regulation pathways related to mRNA splicing and apoptosis. More importantly, indisulam caused mis-splicing of RNA transcripts including p73 isoforms ΔNp73 and TAp73 which have opposite roles in apoptosis regulation. Indisulam increased TAp73 expression and triggered mitochondrial apoptosis independent of p53 status in HeLa cells. In summary, our data suggests that indisulam has therapeutic potential in cervical cancer, representing an attractive strategy in p53-disrupted cancers and should be further investigated.


Inferior Vena Cava Filter Resulting in Perforation and Massive Retroperitoneal Hematoma Presenting as Acute Onset of Lower Extremity Weakness.
Perforation of inferior vena cava (IVC) filter struts is a common incidental finding on postoperative computed tomography (CT) scans that is not associated with bleeding or major complications. However, in rare circumstances, it can be associated with hemorrhage requiring immediate removal. We present a case of a 62-year-old man who developed abdominal pain and right lower extremity weakness 2 weeks after treatment of a pulmonary embolism with IVC filter placement and anticoagulation. A CT scan revealed a large right-sided retroperitoneal hematoma with active extravasation from the IVC filter struts that had perforated the IVC wall. He underwent a hybrid operation with endovascular retrieval of the IVC filter and concomitant IVC primary repair combined with evacuation of the hematoma, causing nerve compression. Postoperatively, he regained normal sensory and motor function. Perforation of IVC filter struts is usually asymptomatic, but in rare circumstances, it can cause hemorrhage requiring immediate removal and IVC repair. Surgical intervention is indicated in the setting of a large hematoma with nerve or vessel compression and may require a combined endovascular and open approach.


metAlignID: a high-throughput software tool set for automated detection of trace level contaminants in comprehensive LECO two-dimensional gas chromatography time-of-flight mass spectrometry data.
A new alternative data processing tool set, metAlignID, is developed for automated pre-processing and library-based identification and concentration estimation of target compounds after analysis by comprehensive two-dimensional gas chromatography with mass spectrometric detection. The tool set has been developed for and tested on LECO data. The software is developed to run multi-threaded (one thread per processor core) on a standard PC (personal computer) under different operating systems and is as such capable of processing multiple data sets simultaneously. Raw data files are converted into netCDF (network Common Data Form) format using a fast conversion tool. They are then preprocessed using previously developed algorithms originating from metAlign software. Next, the resulting reduced data files are searched against a user-composed library (derived from user or commercial NIST-compatible libraries) (NIST=National Institute of Standards and Technology) and the identified compounds, including an indicative concentration, are reported in Excel format. Data can be processed batch wise. The overall time needed for conversion together with processing and searching of 30 raw data sets for 560 compounds is routinely within an hour. The screening performance is evaluated for detection of pesticides and contaminants in raw data obtained after analysis of soil and plant samples. Results are compared to the existing data-handling routine based on proprietary software (LECO, ChromaTOF). The developed software tool set, which is freely downloadable at www.metalign.nl, greatly accelerates data-analysis and offers more options for fine-tuning automated identification toward specific application needs. The quality of the results obtained is slightly better than the standard processing and also adds a quantitative estimate. The software tool set in combination with two-dimensional gas chromatography coupled to time-of-flight mass spectrometry shows great potential as a highly-automated and fast multi-residue instrumental screening method.


Responsibility of citizens in food safety social co-governance in the context of China.
This study aims to identify all actors that hold some responsibility for ensuring food safety based on the complete food supply chain in the context of China's current circumstances. The study was conducted among citizens in Wuxi, Jiangsu, China. All citizens fully understood the purpose of the study and voluntarily agreed to participate. From December 10 to 14, 2020, a total of 398 valid samples were collected by the researchers using a structured questionnaire. Survey data were assessed using best-worst scaling and a mixed logit model from the perspective of citizen responsibility. In descending order, responsibility for ensuring food safety goes from food producers and traders (including producers, distributors, and retailers) to the government, social organizations, news media, and finally to citizens. Food producers and traders are the actors who should take the greatest responsibility, whereas citizens bear the least responsibility. The responsibility of citizens in food safety co-governance should be recognized but it should not be arbitrarily extended.


Pain exposure physical therapy (PEPT) compared to conventional treatment in complex regional pain syndrome type 1: a randomised controlled trial.
To compare the effectiveness of pain exposure physical therapy (PEPT) with conventional treatment in patients with complex regional pain syndrome type 1 (CRPS-1) in a randomised controlled trial with a blinded assessor. The study was conducted at a level 1 trauma centre in the Netherlands. 56 adult patients with CRPS-1 participated. Three patients were lost to follow-up. Patients received either PEPT in a maximum of five treatment sessions, or conventional treatment following the Dutch multidisciplinary guideline. Outcomes were assessed at baseline and at 3, 6 and 9 months after randomisation. The primary outcome measure was the Impairment level Sum Score--Restricted Version (ISS-RV), consisting of visual analogue scale for pain (VAS-pain), McGill Pain Questionnaire, active range of motion (AROM) and skin temperature. Secondary outcome measures included Pain Disability Index (PDI); muscle strength; Short Form 36 (SF-36); disability of arm, shoulder and hand; Lower Limb Tasks Questionnaire (LLTQ); 10 m walk test; timed up-and-go test (TUG) and EuroQol-5D. The intention-to-treat analysis showed a clinically relevant decrease in ISS-RV (6.7 points for PEPT and 6.2 points for conventional treatment), but the between-group difference was not significant (0.96, 95% CI -1.56 to 3.48). Participants allocated to PEPT experienced a greater improvement in AROM (between-group difference 0.51, 95% CI 0.07 to 0.94; p=0.02). The per protocol analysis showed larger and significant between-group effects on ISS-RV, VAS-pain, AROM, PDI, SF-36, LLTQ and TUG. We cannot conclude that PEPT is superior to conventional treatment for patients with CRPS-1. Further high-quality research on the effects of PEPT is warranted given the potential effects as indicated by the per protocol analysis. NCT00817128 and NTR 2090.


The precursors of fecapentaenes: purification and properties of a novel plasmalogen.
Fecapentaene-12 and fecapentaene-14 are genotoxic poly-unsaturated ether-lipids produced by the colonic microflora in humans and pigs. Although the fecapentaenes have been extensively characterized, little is known about the nature of the precursors from which they are produced. We purified one form of these precursors from feces of an individual who excreted high levels of fecapentaene-12 and its precursors. Purification was carried out by a series of extractions and precipitation in organic solvents followed by silica and amine high performance liquid chromatography. The purified precursor had identical UV spectral characteristics as the fecapentaenes indicating that it contained the same ether-linked pentaenyl functional group. However, it was not mutagenic. The precursor was amphiphilic in nature, behaving like a synthetic "model" ether-phospholipid on silica and C18 thin layer chromatography. When incorporated into phosphatidylcholine micelles it could be hydrolyzed in vitro by a combination of lipase and phospholipase C to fecapentaene-12. Our findings indicate that the general structure of this precursor is that of a phospholipid, specifically a plasmalogen--the exact structures of which remain to be determined.


Pseudomonas aeruginosa quorum-sensing signal molecules induce IL-8 production by human corneal epithelial cells.
The aim of the present study was to evaluate whether the quorum-sensing molecules of Pseudomonas aeruginosa could induce the production of interleukin-8 (IL-8) in human corneal epithelial (HCE) cells in vitro. A confluent monolayer of immortalized HCE cells was treated with 12.5 to 50 microM n-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) or n-butanoyl-L-homoserine lactone (BHL) for 18 hours, or challenged with a wild-type P. aeruginosa PAO1 and its quorum-sensing mutants PAO-JP1 (lasI(-)), PDO100 (rhlI(-)), and PAO-JP2 (lasI(-)/rhlI(-)) for 1 hour. The levels of IL-8 in the culture supernatants were determined using an enzyme-linked immunosorbent assay. OdDHL stimulated the production of IL-8 in HCE cells in a dose dependent manner. IL-8 production was seen with low concentrations of BHL (12.5 and 25 microM), but not at higher levels. There was significantly less IL-8 production in the HCE cells challenged with quorum-sensing mutants compared with the wild-type strain PAO1-challenged cells. These findings suggest that quorum-sensing signal molecules OdDHL and BHL may directly contribute to the induction of the inflammatory response in Pseudomonas keratitis.


Central giant cell lesion of the jaws: study of CCND1 gene amplification and p16INK4a protein levels.
Central giant cell lesions (CGCLs) are uncommon benign jaw lesions with uncertain etiology and a variable clinical behavior. In neoplasms, alterations in molecules involved in the G1/S checkpoint are frequently found. Loss of p16(INK4a) expression or overexpression of cyclin D1 may stimulate cell proliferation. The purpose of this study was to analyze CCND1 gene amplification and the expression of p16(INK4a) in CGCLs. Structural analysis of the CCND1 was performed using chromogenic in situ hybridization. Immmunohistochemistry was used to identify p16(INK4a) protein levels. Statistical analysis correlated the two biomarkers with clinical behavior and between each other. Twenty-four lesions were included, being 11 aggressive and 13 non-aggressive. Moderate/high-level CCND1 amplification was found in 12 lesions. Also, immunoreactivity for p16(INK4a) was present in 12 cases, mainly in mononuclear cells. There was a significantly higher level of p16(INK4a) expression in mononuclear cells of non-aggressive lesions and lesions with moderate/high-level CCND1 amplification in mononuclear cells. It could be speculated that some CGCLs may develop as a true benign neoplasm. The higher expression of p16(INK4a) in non-aggressive lesions and in cases with moderate/high-level CCND1 amplification may show that these molecules have a role in CGCLs.


Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder.
Few reports describe the influence pregnancy has on the annualized relapse rate (ARR) in neuromyelitis optica spectrum disorder (NMOSD). To examine pregnancy-related attacks (attacks during pregnancy or within 1 year postpartum) and identify the risk factors for an attack in Japanese NMOSD patients. We retrospectively reviewed 139 Japanese women whom had aquaporin-4 (AQP4) antibody-positive NMOSD. Among the 114 patients with information, 47 women had 56 pregnancies. We compared the ARR before, during and after pregnancy. Of the 47 NMOSD patients with pregnancy, 22 women (46.8%) had a pregnancy-related attack of the disease (either an onset event or a relapse). The ARR was significantly higher in the first 3 months postpartum (1.80 ± 2.04), than before the pregnancy (0.57 ± 1.16; p = 0.0043) and did not significantly decrease during pregnancy. The ARR before hospitalization and treatment was analyzable in 55 patients without pregnancy and was 1.09 ± 1.17. Among the 11 patients with onset before pregnancy, nine patients had a pregnancy-related attack with a relapse in the previous year, and their immunosuppression was discontinued or made to be at low doses; while the two patients on higher-dose therapies were relapse-free. In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.


Reduced Purkinje cell density in Huntington's disease.
We studied, in a "blind" and quantitative fashion, the density of cerebellar Purkinje cells in 17 adult cases of Huntington's disease (HD), 17 patients with other movement disorders, 17 with schizophrenia, and 23 normal controls. There was a highly significant reduction in Purkinje cell density in HD compared with any of the other three groups. A much smaller difference in neuronal density between patients with other movement disorders and normal controls was barely significant. Eight of the 17 HD patients and only 1 of the other 57 subjects had Purkinje cell density less than 50% of the mean for the normal controls. The low density of Purkinje cells in HD could not be attributed to aging, seizures, or cause of death, nor was it merely a part of a generalized brain atrophy. The loss of large Purkinje cells suggests that the neuronal loss in HD may not be restricted to small and medium-size neurons.


The Effects of Migration and Limited Medical Resources of the Transmission of SARS-CoV-2 Model with Two Patches.
The sudden outbreak of SARS-CoV-2 has caused the shortage of medical resources around the world, especially in developing countries and underdeveloped regions. With the continuous increase in the duration of this disease, the control of migration of humans between regions or countries has to be relaxed. Based on this, we propose a two-patches mathematical model to simulate the transmission of SARS-CoV-2 among two-patches, asymptomatic infected humans and symptomatic infected humans, where a half-saturated detection rate function is also introduced to describe the effect of medical resources. By applying the methods of linearization and constructing a suitable Lyapunov function, the local and global stability of the disease-free equilibrium of this model without migration is obtained. Further, the existence of forward/backward bifurcation is analyzed, which is caused by the limited medical resources. This means that the elimination or prevalence of the disease no longer depends on the basic reproduction number but is closely related to the initial state of asymptomatic and symptomatic infected humans and the supply of medical resources. Finally, the global dynamics of the full model are discussed, and some numerical simulations are carried to explain the main results and the effects of migration and supply of medical resources on the transmission of disease.


Association Between Emergency Medical Service Agency Volume and Mortality in Trauma Patients.
Evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies. Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS. Retrospective analysis of prospective cohort including eight trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18-90 years old with injury severity scores >9 transported from scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and mortality. 33,511 were included with a median EMS agency volume of 374 patients annually (IQR 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (aOR 0.95; 95%CI 0.92-0.99, P=0.03) and 3% decreased odds of 24-hour mortality (aOR 0.97; 95%CI 0.95-0.99, P=0.04). Pre-specified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% versus 4.8%, P<0.01). A higher volume of trauma patients transported at the EMS agency-level is associated with improved early survival. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.


Iron: metabolism, toxicity and therapy.
This paper is an overview on iron metabolism, iron toxicity and therapeutics against this toxicity. The attention has been focused on: i) the solubilization of iron by living organisms; ii) the iron metabolism in human; iii) the toxicity of iron (Fe-catalyzed reduction of oxygen, Fenton reaction, decomposition of lipid peroxides); iv) the natural protective mechanisms; v) the relations between iron, free radicals and human diseases; and vi) the iron overload and its treatment.


Ectopic Splicing Disturbs the Function of Xist RNA to Establish the Stable Heterochromatin State.
Non-coding Xist RNA plays an essential role in X chromosome inactivation (XCI) in female mammals. It coats the X chromosome in cis and mediates the recruitment of many proteins involved in gene silencing and heterochromatinization. The molecular basis of how Xist RNA initiates chromosomal silencing and what proteins participate in this process has been extensively studied and elucidated. Its involvement in the establishment and maintenance of the X-inactivated state is, however, less understood. The Xist IVS allele we previously reported is peculiar in that it can initiate XCI but fails to establish the inactive state that is stably maintained and, therefore, may provide an opportunity to explore how Xist RNA contributes to establish a robust heterochromatin state. Here we demonstrate that ectopic splicing taking place to produce Xist IVS RNA disturbs its function to properly establish stable XCI state. This finding warrants the potential of Xist IVS RNA to provide further insight into our understanding of how Xist RNA contributes to establish sustainable heterochromatin.


SARS-CoV-2 seroprevalence worldwide: a systematic review and meta-analysis.
COVID-19 has been arguably the most important public health concern worldwide in 2020, and efforts are now escalating to suppress or eliminate its spread. In this study we undertook a meta-analysis to estimate the global and regional seroprevalence rates in humans of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to assess whether seroprevalence is associated with geographical, climatic and/or sociodemographic factors. We systematically reviewed PubMed, Scopus, Embase, medRxiv and bioRxiv databases for preprints or peer-reviewed articles (up to 14 August 2020). Study eligibility criteria were population-based studies describing the prevalence of anti-SARS-CoV-2 (IgG and/or IgM) serum antibodies. Participants were people from different socioeconomic and ethnic backgrounds (from the general population), whose prior COVID-19 status was unknown and who were tested for the presence of anti-SARS-CoV-2 serum antibodies. We used a random-effects model to estimate pooled seroprevalence, and then extrapolated the findings to the global population (for 2020). Subgroup and meta-regression analyses explored potential sources of heterogeneity in the data, and relationships between seroprevalence and sociodemographic, geographical and/or climatic factors. In total, 47 studies involving 399 265 people from 23 countries met the inclusion criteria. Heterogeneity (I2 = 99.4%, p < 0.001) was seen among studies; SARS-CoV-2 seroprevalence in the general population varied from 0.37% to 22.1%, with a pooled estimate of 3.38% (95%CI 3.05-3.72%; 15 879/399 265). On a regional level, seroprevalence varied from 1.45% (0.95-1.94%, South America) to 5.27% (3.97-6.57%, Northern Europe), although some variation appeared to relate to the serological assay used. The findings suggested an association of seroprevalence with income levels, human development indices, geographic latitudes and/or climate. Extrapolating to the 2020 world population, we estimated that 263.5 million individuals had been exposed or infected at the time of this study. This study showed that SARS-CoV-2 seroprevalence varied markedly among geographic regions, as might be expected early in a pandemic. Longitudinal surveys to continually monitor seroprevalence around the globe will be critical to support prevention and control efforts, and might indicate levels of endemic stability or instability in particular countries and regions.


Docking, molecular dynamics and QM/MM studies to delineate the mode of binding of CucurbitacinE to F-actin.
CucurbitacinE (CurE) has been known to bind covalently to F-actin and inhibit depolymerization. However, the mode of binding of CurE to F-actin and the consequent changes in the F-actin dynamics have not been studied. Through quantum mechanical/molecular mechanical (QM/MM) and density function theory (DFT) simulations after the molecular dynamics (MD) simulations of the docked complex of F-actin and CurE, a detailed transition state (TS) model for the Michael reaction is proposed. The TS model shows nucleophilic attack of the sulphur of Cys257 at the β-carbon of Michael Acceptor of CurE producing an enol intermediate that forms a covalent bond with CurE. The MD results show a clear difference between the structure of the F-actin in free form and F-actin complexed with CurE. CurE affects the conformation of the nucleotide binding pocket increasing the binding affinity between F-actin and ADP, which in turn could affect the nucleotide exchange. CurE binding also limits the correlated displacement of the relatively flexible domain 1 of F-actin causing the protein to retain a flat structure and to transform into a stable "tense" state. This structural transition could inhibit depolymerization of F-actin. In conclusion, CurE allosterically modulates ADP and stabilizes F-actin structure, thereby affecting nucleotide exchange and depolymerization of F-actin.


Global evaluation of carbon neutrality and peak carbon dioxide emissions: current challenges and future outlook.
With the acceleration of urbanization and industrialization, carbon neutrality and peak carbon dioxide emissions have become common sustainability goals worldwide. However, there are few literature statistics and econometric analyses targeting carbon neutrality and peak carbon dioxide emissions, especially the publication trends, geographic distribution, citation literature, and research hotspots. To conduct an in-depth analysis of existing research fields and future perspectives in this research area, 1615 publications from the Web of Science Core Collection, between 2010 and 2020, were evaluated by using three analysis tools, under the framework of the bibliometrics method. These publications are distributed between the start-up (2010-2015) and the stable development (2016-2020) phases. Cluster analysis suggests three areas of ongoing research: energy-related carbon emissions, methane emissions, and energy biomass. Overall, future trends in this field include cumulative carbon emissions, the residential building sector, methane emission measurement, nitrogen fertilization, land degradation neutrality, and sciamachy satellite methane measurement. Finally, this paper further examines the most comprehensive coverage of nitrogen fertilization and the most recent research of the residential building sector. In view of the statistical clusters from 1615 publications, this paper provides new insights and perspectives for climate-environment-related researchers and policymakers. Specifically, countries could apply nitrogen fertilizer to crops according to the conditions of different regions. Additionally, experiences from developed countries could be learned from, including optimizing the energy supply structure of buildings and increasing the use of clean energy to reduce CO2 emissions from buildings.


Unique antigens on neoplastic cells of the soft shell clam Mya arenaria.
Soft shell clams (Mya arenaria) are commonly found in coastal waters of both the eastern and western United States. These invertebrates, which have an open circulatory system, may develop neoplasms of the haemolymph which ultimately kill the host. In this study we have 1) recorded the prevalence of hematopoietic neoplasms (HN) in Mya arenaria within a 50 mile radius of Woods Hole, Massachusetts and 2) utilized cells from one HN bearing clam to generate a series of monoclonal antibodies. Our data show that determinants are expressed on HN cells which are not detected on normal clam haemocytes, suggesting separate ontogenetic pathways of cell differentiation.


Characterization and expression analysis of WRKY genes during leaf and corolla senescence of Petunia hybrida plants.
Several families of transcription factors (TFs) control the progression of senescence. Many key TFs belonging to the WRKY family have been described to play crucial roles in the regulation of leaf senescence, mainly in Arabidopsis thaliana. However, little is known about senescence-associated WRKY members in floricultural species. Delay of senescence in leaves and petals of Petunia hybrida, a worldwide ornamental crop are highly appreciated traits. In this work, starting from 28 differentially expressed WRKY genes of A. thaliana during the progression of leaf senescence, we identified the orthologous in P. hybrida and explored the expression profiles of 20 PhWRKY genes during the progression of natural (age-related) leaf and corolla senescence as well as in the corollas of flowers undergoing pollination-induced senescence. Simultaneous visualization showed consistent and similar expression profiles of PhWRKYs during natural leaf and corolla senescence, although weak expression changes were observed during pollination-induced senescence. Comparable expression trends between PhWRKYs and the corresponding genes of A. thaliana were observed during leaf senescence, although more divergence was found in petals of pollinated petunia flowers. Integration of expression data with phylogenetics, conserved motif and cis-regulatory element analyses were used to establish a list of candidates that could regulate more than one senescence process. Our results suggest that several members of the WRKY family of TFs are tightly linked to the regulation of senescence in P. hybrida. The online version contains supplementary material available at 10.1007/s12298-022-01243-y.


Anti-inflammatory properties of griseofulvin.
Anti-inflammatory activity of griseofulvin has been investigated in comparison with indomethacin and flufenamic acid. In vitro, griseofulvin has been proved the most effective of these agents in suppressing the contractions of smooth muscle preparations induced by a variety of proposed mediators of inflammation, i.e. histamine, 5-hydroxy-tryptamine, bradykinin and prostaglandin E2. In vivo, griseofulvin was unable to modify dextran oedema but suppressed carrageenin oedema, although its activity was poor when compared to that exhibited by indomethacin and flufenamic acid. When tested in rat pleurisy induced by dextran or homologous serum griseofulvin was able to prevent polymorph migration into the pleural space while mononuclears remained virtually unaffected. In contrast indomethacin and flufenamic acid mainly suppressed mononuclear migration while polymorphs resulted only slightly affected. Similar results have been exhibited by the drugs when tested on mononuclear turnover in pleural cavities from normal rats. Results are discussed in the light of the clinically established ability of griseofulvin to prevent cutaneous inflammatory reactions as well as of its effectiveness in the treatment of several polyarthritic syndromes.


In vitro metabolism of [3H] corticosterone by mammary glands from lactating rats. Isolation and identification of 21-acyl[3H]corticosterone.
[3H] Corticosterone undergoes extensive 21-acylation on incubation with minced mammary glands from lactating rats. A purified 21-acyl [3H] corticosterone fraction was obtained by subjecting extracts of the incubated tissues to Sephadex LH-20 column chromatography followed by partitioning between n-heptane/methanol. The methanol extracts were chromatographed consecutively on columns of silica gel and C18-silanized (reverse-phase) silica gel. The radioactive product was methoximated and re-chromatographed on the reverse-phase column. Mass spectral analysis of the 21-acyl [3H] corticosterone 3,20-dimethoxime and synthetic corticosterone 21-oleate 3,20-dimethoxime suggested identity. Confirmation of the precise nature of the 21-acyl moiety was obtained by isotope dilution analysis of the underivatized radiometabolite with corticosterone 21-oleate. The composition of the 21-acyl [3H] corticosterone fraction (i.e. before extensive purification) was ascertained by isotope dilution analysis with various corticosterone esters. It appears that [3H] corticosterone 21-oleate is a major component of this fraction, representing 80% of the radioactivity; [3H] corticosterone 21-linoleate is a minor component, i.e. 8.6%. [3H] Corticosterone 21-palmitate, [3H] corticosterone 21-arachidonate, and [3H] corticosterone 21-stearate, if indeed present, constitute considerably less than 14, 6, and 2%, respectively, of the radiometabolite fraction. It is suggested that bioacylation of corticosterone serves to modulate the biological action of the glucocorticoid hormone on the mammary glands during lactation.


Timing RNA polymerase pausing with TV-PRO-seq.
Transcription of many genes in metazoans is subject to polymerase pausing, which is the transient stop of transcriptionally engaged polymerases. This is known to mainly occur in promoter-proximal regions but it is not well understood. In particular, a genome-wide measurement of pausing times at high resolution has been lacking. We present here the time-variant precision nuclear run-on and sequencing (TV-PRO-seq) assay, an extension of the standard PRO-seq that allows us to estimate genome-wide pausing times at single-base resolution. Its application to human cells demonstrates that, proximal to promoters, polymerases pause more frequently but for shorter times than in other genomic regions. Comparison with single-cell gene expression data reveals that the polymerase pausing times are longer in highly expressed genes, while transcriptionally noisier genes have higher pausing frequencies and slightly longer pausing times. Analyses of histone modifications suggest that the marker H3K36me3 is related to the polymerase pausing.


Intraverbal behavior and verbal conditional discriminations in typically developing children and children with autism.
Individuals with autism often experience difficulty acquiring a functional intraverbal repertoire, despite demonstrating strong mand, tact, and listener skills. This learning problem may be related to the fact that the primary antecedent variable for most intraverbal behavior involves a type of multiple control identified as a verbal conditional discrimination (VC(D)). The current study is a descriptive analysis that sought to determine if there is a general sequence of intraverbal acquisition by typically developing children and for children with autism, and if this sequence could be used as a framework for intraverbal assessment and intervention. Thirty-nine typically developing children and 71 children with autism were administered an 80-item intraverbal subtest that contained increasingly difficult intraverbal questions and VC(D)s. For the typically developing children the results showed that there was a correlation between age and correct intraverbal responses. However, there was variability in the scores of children who were the same age. An error analysis revealed that compound VC(D)s were the primary cause of errors. Children with autism made the same types of errors as typically developing children who scored at their level on the subtest. These data suggest a potential framework and sequence for intraverbal assessment and intervention.


Biophysical compartment models for single-shell diffusion MRI in the human brain: a model fitting comparison.
Clinically oriented studies commonly acquire diffusion MRI (dMRI) data with a single non-zerob-value (i.e. single-shell) and diffusion weighting ofb= 1000 s mm-2. To produce microstructural parameter maps, the tensor model is usually used, despite known limitations. Although compartment models have demonstrated improved fits in multi-shell dMRI data, they are rarely used for single-shell parameter maps, where their effectiveness is unclear from the literature. Here, various compartment models combining isotropic balls and symmetric tensors were fitted to single-shell dMRI data to investigate model fitting optimization and extract the most information possible. Full testing was performed in 5 subjects, and 3 subjects with multi-shell data were included for comparison. The results were tested and confirmed in a further 50 subjects. The Markov chain Monte Carlo (MCMC) model fitting technique outperformed non-linear least squares. Using MCMC, the 2-fibre-orientation mono-exponential ball and stick model (BSME2) provided artifact-free, stable results, in little processing time. The analogous ball and zeppelin model (BZ2) also produced stable, low-noise parameter maps, though it required much greater computing resources (50 000 burn-in steps). In single-shell data, the gamma-distributed diffusivity ball and stick model (BSGD2) underperformed relative to other models, despite being an often-used software default. It produced artifacts in the diffusivity maps even with extremely long processing times. Neither increased diffusion weighting nor a greater number of gradient orientations improvedBSGD2fits. In white matter (WM), the tensor produced the best fit as measured by Bayesian information criterion. This result contrasts with studies using multi-shell data. However, in crossing fibre regions the tensor confounded geometric effects with fractional anisotropy (FA): the planar/linear WM FA ratio was 49%, whileBZ2andBSME2retained 76% and 83% of restricted fraction, respectively. As a result, theBZ2andBSME2models are strong candidates to optimize information extraction from single-shell dMRI studies.


Association between maximum standarised uptake value (SUV) and local control in patients with oropharyngeal carcinoma treated with radiotherapy.
To analyse the prognostic ability of the maximum standardised uptake value (SUVmax) on local disease control in patients with oropharyngeal carcinoma treated with radiotherapy. Retrospective study of 105 patients with oropharyngeal carcinomas treated with radiotherapy, including chemo- and bio-radiotherapy, and who had a PET-CT scan prior to the start of treatment. Patients with a SUVmax value higher than 17.2 at the primary tumour site had a significantly higher risk of local recurrence. The 5-year local recurrence-free survival for patients with SUVmax less than or equal to 17.2 (n = 71) was 86.5% (95% CI 78.2-94.7 %), and for patients with SUVmax greater than 17.2 (n = 34) it was 55.8% (95% CI 36.0-75.6 %) (P = 0.0001). This difference in local control was maintained regardless of patients' HPV status. Specific survival was similarly lower for patients with a SUV greater than 17.2. The 5-year specific survival for patients with SUVmax greater than 17.2 was 39.5% (95% CI: 20.6-58.3 %), significantly shorter than that of patients with SUVmax equal to or less than 17.2, which was 77.3% (95% CI: 66.9-87.6 %) (P = 0.0001). Patients with oropharyngeal carcinomas treated with radiotherapy with a SUVmax greater than 17.2 at the level of the primary tumour site had a significantly higher risk of local recurrence.


Cardiorespiratory and metabolic changes during yoga sessions: the effects of respiratory exercises and meditation practices.
The novelty of this study was to investigate the changes in cardiorespiratory and metabolic intensity brought about by the practice of pranayamas (breathing exercises of yoga) and meditation during the same hatha-yoga session. The technique applied was the one advocated by the hatha-yoga system. Nine yoga instructors-five females and four males, mean age of 44+/-11, 6, were subjected to analysis of the gases expired during three distinct periods of 30 min: rest, respiratory exercises and meditative practice. A metabolic open circuit computerized system was applied (VO2000, MedGraphics-USA). The oxygen uptake (VO(2)) and the carbon dioxide output (VCO(2)) were statistically different (P <or= 0.05) during meditation and pranayama practices when compared with rest. The heart rate also suffered relevant reductions when results at rest were compared with those during meditation. A smaller proportion of lipids was metabolized during meditation practice compared with rest. The results suggest that the meditation used in this study reduces the metabolic rate whereas the specific pranayama technique in this study increases it when compared with the rest state.


Acoustic radiation force impulse (ARFI) elastography in the evaluation of renal parenchymal stiffness in patients with ureteropelvic junction obstruction.
To investigate the role of acoustic radiation force impulse (ARFI) elastography in the detection of renal parenchymal damage in kidneys with and without ureteropelvic junction obstruction (UPJO). Twenty-five pediatric patients with a diagnosis of UPJO who underwent surgery and 15 pediatric patients with conservatively managed UPJO were prospectively evaluated with ARFI elastography. Sixteen healthy volunteers constituted the control group. Shear wave velocity (SWV) measurements in the upper, mid, and lower poles of the affected kidney were performed. SWV values of kidneys based on presence of UPJO and hydronephrosis grade were compared. The correlation of SWV values with residual renal function obtained from diethylenetriaminepentaacetic acid or mercaptoacetyltriglycine-3 renal scan was evaluated. Significantly, higher SWV values were found in control kidneys compared to kidneys affected by UPJO. The median SWVs were 2.82 (2.51-3.07) m/s for the control kidneys and 2.36 (2.09-2.53) m/s for the kidneys in the UPJO group (p < 0.001). When UPJO patients were grouped according to the grade of hydronephrosis, grade 0 hydronephrotic kidneys [2.35 (2.11-2.50) m/s] and grade 3-4 hydronephrotic kidneys [1.86 (1.96-2.25) m/s] had significantly lower SWV values compared to grade 1-2 hydronephrotic kidneys [2.62 (2.37-2.90) m/s] (p < 0.05). ARFI as a noninvasive, radiation-free procedure for evaluating parenchymal stiffness may prove useful in the diagnostic work-up and follow-up of children with UPJO-induced renal disease.


Length variations of the poly(T) tract at the exon 3 splice acceptor site of the choroideremia gene.
By using the single strand conformational analysis to search for point mutations in the choroideremia gene, we have identified an intronic polymorphism within the intron 2 of the CHM gene. We have studied the frequency of this polymorphism in the population from South of France.


Aspirin use and cardiovascular events in social networks.
We tested whether friends' and family members' cardiovascular health events and also their own aspirin use are associated with the likelihood that an individual takes aspirin regularly. Analyses were based on longitudinal data on 2724 members of the Framingham Heart Study (based in Massachusetts, U.S.A.) who were linked to friends and family members who were also participants in the same study. Men were more likely to take aspirin if a male friend had recently been taking aspirin, and women were more likely to take aspirin if a brother had recently been taking aspirin. Men were also more likely to take aspirin if a brother recently had a cardiovascular event, and women were more likely to take aspirin if a female friend recently experienced a cardiovascular event. Aspirin use is correlated with the health and behavior of friends and family. These findings add to a growing body of evidence which suggests that behavioral changes that promote cardiovascular health may spread through social networks.


[Clinico-psychopathologic features of remissions and work capacity among schizophrenic patients with a continuous of shift-like progressive course].
The author describes 5 clinical variants isolated during clinico-psychopathological analysis of 102 schizophrenic patients with a continuous and attacklike-progressive course of the disease. The indices of socio-labor rehabilitation in patients with affective, asthenical and psychopathlike remissions were rather good. And on the contrary, in cases of residual productive and apathic remissions there were only single cases of satisfactory sociolabor rehabilitation.


Association of Interleukin-10 -1082G > A Polymorphism with Susceptibility to Preeclampsia: A Systematic Review and Meta-Analysis Based on 21 Studies.
Background: Previous studies have reported the association between IL-10 -1082 G > A polymorphism and preeclampsia risk, but the results remained controversial. Therefore, this meta-analysis was performed to evaluate the association of IL-10 -1082 G > A polymorphism with preeclampsia risk.Methods: We searched PubMed, ISI Web of Knowledge and CNKI databases to identify eligible studies up to September 05, 2019.Results: A total of 21 case-control studies with 3,510 cases and 5,874 controls were selected. The results revealed that IL-10 -1082 G > A polymorphism was significantly associated with an increased risk of preeclampsia under the recessive model (AA vs. AG + GG: OR = 1.191, 95% CI = 1.018-1.394, P = 0.029). Stratified analyses by ethnicity revealed a significantly increased risk of preeclampsia in Asian and mixed populations, but not in Caucasians. Moreover, there was a significant association among Chinese and Brazilian.Conclusions: Our results showed that IL-10 -1082 G > A polymorphism was significantly associated with an increased risk of preeclampsia.


Effect of pH on tolerance of Hormidium rivulare to zinc and copper.
The toxicity of zinc to a population of Hormidium rivulare isolated from an acid mine drainage was shown to be least at the optimum pH range for the growth of the alga, pH 3.5-4.0; toxicity increases markedly at higher pH values. Calcium clearly antagonizes the toxicity of zinc. Populations of H. rivulare isolated from higher pH values and which are resistant to zinc, are also especially resistant to low pH values, although they are unlikely ever to encounter such values naturally. Nevertheless raised levels of calcium bring about only a slight improvement of growth at very low pH values in the absence of zinc, so the mechanisms of pH and zinc tolerance are not the same. Although the acid stream population grows in the field in an environment with rather similar levels of zinc and copper, copper is less toxic than zinc at pH 3.5, but much more toxic than zinc at pH 6.0.


A rapid method for assay of branched-chain keto acid decarboxylation in cultured cells and its application to prenatal diagnosis of maple syrup urine disease.
A sensitive assay for measurement of branched-chain keto acid decarboxylation in small numbers of fibroblasts or amniotic cells grown in the wells of a microtitre plate using [1-14C]leucine as substrate is described. The method was applied to the amniotic cells from a pregnancy at risk for maple syrup urine disease and a heterozygous fetus predicted.


Genotypic and phenotypic characterization of enterotoxigenic Escherichia coli (ETEC) strains isolated in Rio de Janeiro city, Brazil.
Enterotoxigenic Escherichia coli (ETEC) strains have been implicated as important etiological agents of diarrheal disease, especially in developing countries. This group of microorganisms has been associated with a diverse range of genotypic and phenotypic markers. In the present study, 21 ETEC isolates previously defined according to the toxigenic genotypes, were characterized on the basis of O:H typing, cell adherence patterns, and colonization factors (CFs) antigens. Genetic diversity was investigated by random amplification polymorphic DNA (RAPD-PCR), pulsed-field gel electrophoresis (PFGE) and multilocus enzyme electrophoresis (MLEE). LT-I probe-positive isolates belonged to serotypes ONT:HNT, O7:H24, O48:H21, O88:H25, O148:H28, O159:H17 and O159:H21. ST-h probe-positive isolates belonged to serotypes O159:H17, O148:H28 and O6:H-. Serotypes O148:H28, O159:H17 and O6:H- were associated with the CS6, CFA/I and CS1 CS3 antigens, respectively. Most ETEC strains exhibited a diffuse pattern of adherence to cultured epithelial cells. In general, phenotypic and genotypic characteristics correlated well. RAPD-PCR, PFGE and MLEE showed reproducibility and good discriminatory potential. The application of molecular typing systems allowed the detection of significant diversity among the isolates, indicating a non-clonal origin and revealing intra-serotype variation overlooked by classical epidemiological approaches. The phenotypic and genotypic diversity observed lead us to recommend the use of different typing systems in order to elucidate the epidemiology of ETEC infection.


Selective detection of dihydrogen phosphate anion by fluorescence change with tetraamide-based receptors bearing isoquinolyl and quinolyl moieties.
Novel fluororeceptors 2 and 3 based on tetraamide bearing 1-isoquinolyl and 2-quinolyl moieties were designed and synthesized. Highly selective and significant changes in the UV-vis and fluorescence spectra of the receptors upon the addition of H(2)PO(4)(-) were found. In particular, receptor 3 bearing 2-quinolyl groups shows selective and nearly perfect quenching by H(2)PO(4)(-), whereas 3 shows small or no fluorescence changes by another anion.


Tissue specificity of glycosphingolipids as expressed in pancreas and small intestine of blood group A and B human individuals.
A chemical investigation has been done on blood group active glycosphingolipids of both small intestine and pancreas from two individuals, one blood group A and one blood group B. Total non-acid glycolipid fractions were prepared and the major blood group fucolipids present were purified and structurally characterized by mass spectrometry, proton NMR spectroscopy, and degradation methods. The glycolipid structures identified were a blood group Leb hexaglycosylceramide, a B-hexaglycosylceramide with a type 1 (Gal beta 1 leads to 3GlcNAc) carbohydrate chain, A-hexaglycosylceramides with types 1 and 2 (Gal beta 1 leads to 4GlcNAc) carbohydrate chains, a B-heptaglycosylceramide with a type 1 carbohydrate chain, and A-heptaglycosylceramides with type 1 and 2 carbohydrate chains. In addition several minor glycolipids having more than seven sugar residues were detected by thin-layer chromatography. The small intestine and pancreas had some distinct differences in their expression of the major fucolipids. The small intestine contained only glycolipids based upon type 1 carbohydrate chain while the pancreas had both type 1 and type 2 structures. The intestines contained mainly difucosyl compounds while the pancreas tissues contained both mono- and difucosyl glycolipids. Monofucosylglycolipids based on both types 1 and 2 saccharides were present in one pancreas while the other one contained only monofucosylcomponents based on type 1 chain. The ceramides of the intestinal glycolipids were found to be more hydroxylated (trihydroxy long-chain base, hydroxy fatty acids) compared to the pancreas glycolipids (dihydroxy long-chain base, non-hydroxy fatty acids).


Radiotherapy for parotid IgG4-related disease.
We describe the use of radiotherapy for parotid IgG4-related disease (IgG4-RD), initially misdiagnosed as Kimura's disease, with sustained good partial response in a 37-year-old male. To the best of our knowledge, this is the first reported case of radiation for extra-orbital IgG4-RD, albeit inadvertently.


Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection.
The identification of new high-sensitivity and high-specificity markers for hepatocellular carcinoma (HCC) is essential. We aimed at identifying serum microRNAs (miRNAs) as potential biomarkers for early detection of HCC on top hepatitis C virus (HCV) infection. We investigated serum expression of 13 miRNAs in 384 patients with HCV-related chronic liver disease (192 with HCC, 96 with liver cirrhosis (LC), and 96 with chronic hepatitis C (CHC)) in addition to 96 healthy participants enrolled as a control group. The miRNA expression was performed using real-time quantitative PCR-based SYBR Green custom miRNA arrays. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of miRNA panels for early detection of HCC. Using miRNA panel of miR-122, miR-885-5p, and miR-29b with alpha fetoprotein (AFP) provided high diagnostic accuracy (AUC = 1) for early detection of HCC in normal population while using miRNA panel of miR-122, miR-885-5p, miR-221, and miR-22 with AFP provided high diagnostic accuracy (AUC = 0.982) for early detection of HCC in LC patients. However, using miRNA panel of miR-22 and miR-199a-3p with AFP provided high diagnostic accuracy (AUC = 0.988) for early detection of HCC in CHC patients. We identified serum miRNA panels that could have a considerable clinical use in early detection of HCC in both normal population and high-risk patients.


Isolation, purification and structural investigation of a water-soluble polysaccharide from Solanum lyratum Thunb.
Polysaccharides, extracted from the herbs of Chinese natural Solanum lyratum Thunb (SLT), which is a traditional Chinese medicine with hot water and 0.04 M sodium hydroxide successively, were fractionated and purified by ion-exchange and gel-filtration chromatography. According to methylation, periodate oxidation, NMR spectroscopy, partial and graded acid and enzymic hydrolysis analysis, the results indicated the D-glucan to be linear and to contain both (1-->3)- and (1-->4)-linkages. The anomeric NMR and IR spectra measurements confirmed that the sugar residues were beta-glycosidically linked.


Pre-sliced fruit in school cafeterias: children's selection and intake.
It is often assumed that children avoid fruit in school cafeterias because of higher relative prices and preferences for other foods. Interviews with children reveal that eating whole fresh fruit can be difficult for those with small mouths or braces. Older girls find whole fruits messy and unattractive to eat. To determine the effect of offering pre-sliced fruit in schools on selection and intake. Three of six schools were assigned randomly to serve apples in slices. Three control schools served apples whole. Selection, consumption, and waste of apples were measured prior to and during treatment. Cafeterias in six public middle schools in Wayne County NY in 2011. Participants included all students who purchased lunch on days when data were collected. Treatment schools were provided with a standard commercial fruit slicer, and cafeteria staff members were instructed to use it when students requested apples. Trained researchers recorded how much of each apple was consumed and how much was wasted in both control and treatment schools. Daily apple sales, percentage of an apple serving consumed per student, and percentage of an apple serving wasted per student. Data were analyzed in 2012. Schools that used fruit slicers to pre-slice fruit increased average daily apple sales by 71% compared to control schools (p<0.01). The percentage of students who selected apples and ate more than half increased by 73% (p=0.02) at schools that served pre-sliced fruit, and the percentage that wasted half or more decreased by 48% (p=0.03). Sliced fruit is more appealing to children than whole fruit because it is easier and tidier to eat. This study applies the principle of convenience from behavioral economics and provides an example of a scalable, low-cost environmental change that promotes healthy eating and decreases waste.


The photodegradation of trichloroethylene with or without the NAPL by UV irradiation in surfactant solutions.
The photodegradation of trichloroethene (TCE) with or without nonaqueous phase liquids (NAPL) by ultraviolet irradiation in surfactant solutions was examined in this study. The photodecay of TCE was studied at monochromatic 254nm UV lamps. The effects of the type of surfactants, initial surfactant concentrations, pH levels and NAPL concentrations were examined to explore the photodecay of TCE. All the photodegradation of TCE followed pseudo-first-order decay kinetics at various conditions. It was found that Brij 35 overdose and higher initial pH levels may retard or inhibit the photodecay of TCE, mainly due to protons, intermediate generation and change of surfactant structure in the processes. The optimal condition for TCE photodecay was suggested based on the analysis of kinetics data, from which the reaction mechanism of TCE in the presence of NAPL form was also studied. In general, the reactions of TCE in micellar solution and NAPL pool can be considered as independent pathways due to the low molecule diffusion between the two phases.


Machine learning-based radiomics analysis in predicting the meningioma grade using multiparametric MRI.
To investigate the prediction performance of radiomic models based on multiparametric MRI in predicting the meningioma grade. In all, 229 low-grade [Grade I] and 87 high-grade [Grade II/III] patients with pathologically diagnosed meningiomas were enrolled. Radiomic features from conventional MRI (cMRI), ADC maps and SWI were extracted based on the volume of entire tumor. Classification performance of different radiomic models (cMRI, ADC, SWI, cMRI + ADC, cMRI + SWI, ADC + SWI, and cMRI + ADC + SWI models) was evaluated by a nested LOOCV approach, combining the LASSO feature selection and RF classifier that was trained (1) without subsampling, and (2) with the synthetic minority over-sampling technique (SMOTE). The prediction performance of radiomic models was assessed using ROC curve and AUC of them was compared using Delong's test. The cMRI + ADC + SWI model demonstrated the best performance without or with subsampling, which AUCs were 0.84 and 0.81, respectively. Following the cMRI + ADC + SWI model, the AUC range of the other models was 0.75-0.80 without subsampling, and was 0.71-0.79 with subsampling. Although the cMRI + ADC model and cMRI + SWI model showed higher AUCs than the cMRI model without subsampling (0.77 vs 0.80, P = 0.037 and 0.77 vs 0.80, P = 0.009, respectively), there was no significant difference among these models with subsampling (0.78 vs 0.77, P = 0.552 and 0.78 vs 0.79, P = 0.246, respectively). Multiparametric radiomic model based on cMRI, ADC map and SWI yielded the best prediction performance in predicting the meningioma grade, which might offer potential guidance in clinical decision-making.


Eyelid reconstruction in pachydermoperiostosis.
Our experience with an unusual case of pachydermoperiostosis is described. This case was accompanied by enlargement of the eyelids, excessive secretions, and difficulty in opening the eyes. Partial and serial excisions of the upper and lower eyelids were done to correct the thickened eyelids. As a result of the operations, this patient can open his eyes fully and the secretions have decreased.


Regulation of Mammalian 13-Subunit Cytochrome c Oxidase and Binding of other Proteins: Role of NDUFA4.
Cytochrome c oxidase (CcO) is the final oxygen accepting enzyme complex (complex IV) of the mitochondrial respiratory chain. In contrast to the other complexes (I, II, and III), CcO is highly regulated via isoforms for six of its ten nuclear-coded subunits, which are differentially expressed in species, tissues, developmental stages, and cellular oxygen concentrations. Recent publications have claimed that NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (NDUFA4), originally identified as subunit of complex I, represents a 14th subunit of CcO. Results on CcO composition in tissues from adult animals and the review of data from recent literature strongly suggest that NDUFA4 is not a 14th subunit of CcO but may represent an assembly factor for CcO or supercomplexes (respirasomes) in mitochondria of growing cells and cancer tissues.


[Neuropathological study of incontinentia pigmenti. Anatomical case report (author's transl)].
Report of a case of Incontinentia pigmenti (IP) of the Bloch-Sulzberger type, with neurological features, in a 3 month-old deceased infant. The neuropathological examination revealed signs of a destructive process which had occurred in the perinatal period: ulegyria, cavities of white matter and patchy scar softening of the cerebellar cortex. In addition, there was a diffuse inflammatory process involving the pia-arachnoid and brain tissue: perivascular cuffs of lymphocytes, histiocytes and eosinophilic polymorphs, and mononuclear nodules. No prenatal malformations or vascular lesions were found. These findings are discussed in the light of both the relevant literature on neurological abnormalities in IP and the only already reported neuropathological examination by O'Doherty and Norman (1968). Two main hypotheses might account for the frequency of neurological disturbances in IP, 1. a peculiar sensitivity of the brain to anoxia and/or ischemia: 2. its involvement by the specific inflammatory process which occurs both in the skin as other tissues in this genetically determined disease (Perié et al., 1976).


Accurate-parametric SAR-TL dating protocols for older sediments using quartz.
Thermoluminescence (TL) dating is one of the most significant chronological tools used in Quaternary research. However, for changes in the characteristics of quartz, the larger deviation is still a problem in TL dating, especially with the single-aliquot regeneration-does (SAR) procedure. In the SAR-TL protocol, changes in the characteristics of quartz inevitably cause a shift in the TL peak position and a reduction in the sensitivity of the TL peak during repetitive thermal treatment. In this paper, we studied the optimal TL parameters to minimize the effect of the above problems for TL dating. Based on the optimization experiment combining OSL and TL measurements, the optimal preheat temperature was found to be 300 °C for both silt-sized grains and sand-sized grains, which eliminates the remainder of the 325 °C TL signals and inhibits the 375 °C TL peak position shift. Referring to the test does in SAR-OSL dating protocol, the optimal test doses, 200 Gy and 250 Gy for the silt-sized grains and sand-sized grains respectively, were determined to correct the reduction in TL sensitivity, and they were added to improve the SAR-TL protocol. The improved SAR-TL protocol with the optimal measurement parameters, which we called the accurate-parametric SAR-TL protocol, improves the accuracy of quartz TL dating and expands the range of accurate TL dating. For the experimental doses of 400 Gy and 700 Gy, the relative error of De obtained by the accurate-parametric SAR-TL protocol was less than ±5.5% for both silt-sized grains and sand-sized grains. In addition, we discussed the application conditions of the accurate-parametric SAR-TL protocol and the method that obtains the same level of thermal lag for different luminescence measurement equipment.


Saccharin Test Time as a New Prognostic Predictor of Tympanoplasty.
In India, Chronic suppurative otitis media (CSOM) is a general public health issue leading to hearing loss which can be corrected surgically by Tympanoplasty. By applying predictors for a successful surgery the effectiveness of the surgery can be improved. In this study we aim to determine the usefulness of prognostic factors in predicting outcome of surgery for better patient compliance. 1. To compare MERI scores and saccharin test time in predicting graft uptake and hearing outcomes in Tympanoplasty surgery. A prospective study included all cases of mucosal type of CSOM of either sex according to the inclusion and exclusion criteria. Saccharin clearance time was used to assess Eustachian tube function and Pure Tone Audiometry has been done Pre-operatively to assess Hearing. Risk categories were assigned using MERI scoring chart and severity of disease assessed by otomicroscopy during surgery. Patients were post-operatively followed up to 6 months. Outcomes were assessed using Graft uptake, Hearing improvement and for recurrence of infection, compared with different categories of MERI and Saccharin time. The overall graft uptake was 96.6%. 100% successful graft uptake was seen among normal eustachian tube function. Hearing improvement after surgery may be predicted by saccharin and MERI test. Abnormal Saccharin test shows guarded prognosis in predicting the success of middle ear surgeries. Based on the MERI score and saccharin clearance time, hearing benefit and Surgical success can be assessed and patients can be counselled prior surgery regarding the expected outcome.


Successful retrieval of a plastic bead from the airway of a child by flexible bronchoscopy and a balloon-tipped catheter: A case report and literature review.
Bronchial foreign body aspiration is a critical condition that jeopardizes the respiratory function of children. Prompt diagnosis and removal of the foreign body can reduce occurrence of foreign body complications and mortality. Aspiration of spherical plastic beads is rare, and the bead is difficult to retrieve. An 8-year-old girl developed cough, transient throat wheezing, and intermittent cough after she accidentally inhaled a plastic bead 7 hours ago. Chest computed tomography scan revealed a round shadow 1.2 cm in diameter in the right main bronchus. Foreign body in the right main bronchus. Retrieval by balloon-tipped catheter via flexible bronchoscopy was undertaken. The bead was successfully retrieved and the child recovered uneventfully. Foreign body aspiration in children constitutes a medical emergency in severe cases. Flexible bronchoscopy and balloon-tipped catheter retrieval can be used as an effective noninvasive treatment for aspiration of plastic beads.


B0 insensitive multiple-quantum resolved sodium imaging using a phase-rotation scheme.
Triple-quantum filtering has been suggested as a mechanism to differentiate signals from different physiological compartments. However, the filtering method is sensitive to static field inhomogeneities because different coherence pathways may interfere destructively. Previously suggested methods employed additional phase-cycles to separately acquire pathways. Whilst this removes the signal dropouts, it reduces the signal-to-noise per unit time. In this work we suggest the use of a phase-rotation scheme to simultaneously acquire all coherence pathways and then separate them via Fourier transform. Hence the method yields single-, double- and triple-quantum filtered images. The phase-rotation requires a minimum of 36 instead of six cycling steps. However, destructive interference is circumvented whilst maintaining full signal-to-noise efficiency for all coherences.


Clinical efficacy of renal dosing adjustments of ceftazidime-avibactam in patients affected by carbapenem-resistant Gram-negative infections: A systematic review and meta-analysis of observational studies.
The aim of this study is to assess clinical efficacy of ceftazidime-avibactam for the management of carbapenem-resistant Gram-negative infections in renal patients receiving recommended dosing adjustments compared to those treated with scheduled full-dose. Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 31 December 2021, to retrieve randomized controlled trials or observational studies comparing clinical efficacy of ceftazidime-avibactam in patients affected by carbapenem-resistant Gram-negative infections receiving recommended renal dosing adjustments compared to those treated with scheduled full-dose. Data were independently extracted by the 2 authors, and the quality of included studies was independently assessed according to ROBINS-I tool for observational studies. Mortality rate was selected as primary outcome. Meta-analysis was conducted by including only studies at low or moderate risk of bias providing adjustment for confounders. In total, 1794 articles were screened, and 11 observational studies (1 prospective and 10 retrospective) were included. Serious or critical risk of bias was found in 4 studies, while the other 7 were classified at moderate risk of bias and included in the meta-analysis. Renal dosing adjustments of ceftazidime-avibactam were associated with higher risk of mortality (odds ratio 1.79; 95% confidence interval 1.18-2.72). Renal dosing adjustment of ceftazidime-avibactam seems to be associated with a higher risk of mortality in patients affected by carbapenem-resistant Gram-negative infections. However, residual confounder associated with baseline conditions cannot be excluded. Further prospective studies including larger samples are warranted to definitively address this unmet clinical need.


Ultrasound-induced light transmission change within platelet suspensions as an indirect measure of platelet morphology: preliminary correlation with stirring-induced light transmission change.
Discoid platelets were directionally orientated using stirring or ultrasound, and the change from random orientation was measured by light transmission. Stirring-induced light transmission change (SILTC), already well established as a good indirect indicator of platelet morphology, was compared with ultrasound-induced light transmission change (USILTC) in order to determine whether USILTC may be a similarly good indicator of platelet morphology. Numerous direct comparisons were made between SILTC and USILTC at various static temperatures, and during the dynamic thermal transitions of warming and cooling. Good correlation exists between quantitated SILTC and USILTC values, but the relationship is not exact. Furthermore, single stirring events may considerably distort the relationship under certain conditions. At the ultrasound frequency of 5 MHz and at an estimated peak positive pressure of 2.03 X 10(4) Pa, the USILTC response patterns exhibit a qualitative "spike" pattern for unfixed platelets, which disappears following glutaraldehyde fixation. These preliminary findings are described and discussed in detail, since they suggest that USILTC is a better index of platelet viability than SILTC, although much research is still required in this area.


Isolation and structural characterization of two novel oxidative degradation products of losartan potassium active pharmaceutical ingredient using advanced analytical techniques.
Losartan potassium (losartan) is the most frequently utilized antihypertensive medication in the world. However, partial oxidation of losartan produces toxic by-products that could be harmful to living organisms. Therefore, it is necessary to degrade the losartan and identify the potential toxic oxidative degradation products to minimize their formation during manufacturing, formulation, storage, and packing conditions. Oxidative degradation experiments of losartan were performed according to ICH guidelines. The degradation products were detected using ultra-high-performance liquid chromatography-mass spectrometry analysis, isolated by using preparative HPLC, and identified by using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopic techniques. The degradation products (DP-1, DP-2, and DP-3) were identified as (((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)amino)-2-oxoethylpentanoate, 5-(4'-((2 butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-yl)-1H tetrazol-1-ol, and 5-(4'-((2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1 yl)methyl)-[1,1'-biphenyl]-2-yl)-2H-tetrazol-2-ol, respectively. Forced degradation of losartan potassium API under oxidative condition indicates the formation of two major novel oxidative degradation products (DP-2 and DP-3) and one minor known degradation product (DP-1).Preparative HPLC used for the isolation of the resultant DPs and their structures were successfully established using UHPLC-MS, 1H NMR, 13C NMR, HSQC, HMBC, and HRMS spectroscopic techniques.


Therapeutic strategies for patients with internal carotid or middle cerebral artery occlusion complicated by severe coronary artery disease.
Ischemic stroke is one of major complications of cardiac surgery. Although a current American Heart Association (AHA) guideline states that carotid endarterectomy is probably recommended before or concomitant to coronary artery bypass grafting (CABG) for the carotid stenosis, there is no report that analyzed optimal strategies in cardiac surgery for patients with total occlusion of the internal carotid artery (ICA) or the middle cerebral artery (MCA). Therefore, this preliminary study was aimed to clarify whether preoperative blood flow measurements and prophylactic superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis could reduce the incidence of perioperative ischemic stroke during cardiac surgery in patients with total occlusion of the ICA or MCA. This prospective study included eight patients who were admitted to undergo cardiac surgery including CABG. All of them had total ICA or MCA occlusion on preoperative magnetic resonance (MR) examinations. Preoperative cerebral blood flow and its reactivity to acetazolamide were quantitatively determined in all eight patients using single photon emission computed tomography or positron emission tomography. Preoperative blood flow measurements revealed that two (25%) of eight patients had normal cerebral hemodynamics because of well-developed collaterals. They safely underwent cardiac surgery. However, a marked impairment of cerebral perfusion reserve was identified in six (75%) of eight patients in the ipsilateral hemispheres. Of these, four patients underwent prophylactic STA-MCA anastomosis prior to CABG. Subsequently, they safely underwent CABG without perioperative ischemic stroke. This is the first report suggesting that preoperative identification of hemodynamic compromise and prophylactic STA-MCA anastomosis may reduce perioperative ischemic stroke during cardiac surgery in patients with ICA or MCA occlusion, although further studies are needed to assess the validity.


An automated flow injection system for metal determination by flame atomic absorption spectrometry involving on-line fabric disk sorptive extraction technique.
A novel flow injection-fabric disk sorptive extraction (FI-FDSE) system was developed for automated determination of trace metals. The platform was based on a minicolumn packed with sol-gel coated fabric media in the form of disks, incorporated into an on-line solid-phase extraction system, coupled with flame atomic absorption spectrometry (FAAS). This configuration provides minor backpressure, resulting in high loading flow rates and shorter analytical cycles. The potentials of this technique were demonstrated for trace lead and cadmium determination in environmental water samples. The applicability of different sol-gel coated FPSE media was investigated. The on-line formed complex of metal with ammonium pyrrolidine dithiocarbamate (APDC) was retained onto the fabric surface and methyl isobutyl ketone (MIBK) was used to elute the analytes prior to atomization. For 90s preconcentration time, enrichment factors of 140 and 38 and detection limits (3σ) of 1.8 and 0.4μgL(-1) were achieved for lead and cadmium determination, respectively, with a sampling frequency of 30h(-1). The accuracy of the proposed method was estimated by analyzing standard reference materials and spiked water samples.


Polypropylene film chemical and physical modifications by dielectric barrier discharge plasma treatment at atmospheric pressure.
Dielectric barrier discharge (DBD) technologies have been used to treat a polypropylene film. Various parameters such as treatment speed or electrical power were changed in order to determine the treatment power impact at the polypropylene surface. Indeed, all the treatments were performed using ambient air as gas to oxidize the polypropylene surface. This oxidation level and the surface modifications during the ageing were studied by a wetting method and by X-ray photoelectron spectroscopy (XPS). Moreover polypropylene film surface topography was analyzed by atomic force microscopy (AFM) in order to observe the surface roughness modifications. These topographic modifications were correlated to the surface oxidation by measuring with a lateral force microscope (LFM) the surface heterogeneity. The low ageing effects and the surface reorganization are discussed.


Intestinal mucin antigens in ulcerative colitis and their relationship with malignancy.
The expression of two intestinal mucin-associated antigens large intestine mucin antigen (LIMA) and small intestine mucin antigen (SIMA) were investigated by indirect immunoperoxidase staining of rectal mucosa from patients suffering from ulcerative colitis with (n = 6) and without (n = 31) associated carcinoma and in noncolitic controls (n = 40). The aim was to assess the relationship between antigen patterns and malignant change. SIMA, which is localised predominantly in the small intestine, is virtually undetectable in the normal adult colonic mucosa. However, this antigen is present in the foetal colon and colonic carcinoma. LIMA is expressed in normal colonic mucosa, but absent from the small intestine. LIMA staining patterns were not significantly different among the three groups. In contrast, expression of SIMA was significantly higher in the patients who had developed carcinoma (6/6) than in the noncancer group (7/71) (P less than 0.001). The presence of SIMA was also significantly related to areas of dysplasia compared to normal (P = .03) or inflammation (P less than .05), but it did not differ from mucosa showing "indefinite" atypia. The finding of 31% SIMA-positive biopsies associated with severe inflammation in colitis with active disease, but no evidence of malignancy, is difficult to explain at the present stage. A followup study would be necessary to determine its significance. Perhaps the most important finding is the increased frequency of SIMA-positive foci in histologically normal mucosa in carcinoma patients compared with the noncancer group (P less than .001), suggesting a field change. These observations may be prove useful for the identification of patients who may be at risk of developing carcinoma.


Primary leiomyosarcoma of the pancreas: report of a case treated by local excision and review of the literature.
First described by Ross in 1951, primary pancreatic leiomyosarcoma is a rare mesenchymal tumour of the pancreas, with nonspecific clinical and radiological features and a poor prognosis, if unresectable. A 60-year-old woman presented with abdominal pain. Magnetic resonance imaging (MRI) and computed tomography (CT) scan detected a dishomogeneous egg-shaped 8-cm mass, arising from the pancreatic head, with duodenal compression, without dilation of the Wirsung duct. (18)F-FDG positron-emission tomography (PET)-CT showed a moderate tracer uptake, and the endoscopic ultrasound (US) showed a hypoechoic lesion, arising from the duodenal wall, suspected to be a gastrointestinal stromal tumour (GIST). CEA, CA19-9, NSE, and chromogranin A were normal. At the surgical exploration, a 10-cm mass, adherent to the anterior aspect of the pancreatic head, was found. The lesion was easily separable from the duodenal wall and was totally excised. The frozen intraoperative examination showed a mesenchymal tumour, with spindle-shaped cells, suggesting that a GIST diagnosis was likely. Postoperative course was uneventful. Histology and immunohistochemistry demonstrated a well-differentiated leiomyosarcoma, with five to six mitotic counts per 10 high-power field (HPF) and proliferative index (MIB-1) 10 % (grade 2 according to Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC)), with positive smooth muscle actin, desmin, and caldesmon but negative CD117 (c-kit) and S-100. The patient is alive and asymptomatic 19 months after surgery, without evidences of disease. In the English literature, only 44 cases of primary pancreatic leiomyosarcoma have been reported. If a pancreatic mass suspected for primary pancreatic leiomyosarcoma has no adjacent organ/vessel invasion or distant metastases, surgical resection is the therapy of choice.


The earlier the better: the role of palliative care consultation on aggressive end of life care, hospice utilization, and advance care planning documentation among gynecologic oncology patients.
To evaluate the role of specialty palliative care consultation (PCC) on end of life care outcomes among terminally ill gynecologic oncology patients. Retrospective chart review of currently deceased gynecologic oncology patients seen at a single, academic institution between October 2006 and October 2016. Clinical characteristics and outcomes were examined using descriptive statistics and logistic regression. Two hundred and four patients were eligible. Forty-one percent underwent at least one marker of aggressive care at the end of life. Most (53%) had a PCC prior to death, and of these most were inpatient (89%). Patients with a PCC had higher odds of hospice enrollment before death (OR 2.55, p = 0.016) and higher odds of advance care planning documentation before death (OR 6.79, p = < 0.001). Among patients with an inpatient PCC, 44% underwent a marker of aggressive medical care at the end of life and 82% enrolled in hospice before death. Among patients with an outpatient PCC, 25% underwent a marker of aggressive medical care at the end of life and 92% enrolled in hospice before death. Patients with outpatient PCC were engaged in palliative care longer than patients with inpatient PCC (median 106 days vs. 33 days prior to death). PCC increased hospice enrollment and advance care planning documentation. Patients with outpatient PCC had lower rates of aggressive medical care and higher rates of hospice enrollment when compared to inpatient PCC. Location of initial PCC plays an important role in end of life care outcomes.