Viral oncolysates in patients with advanced ovarian cancer.
Viral oncolysates (VO) derived from two cultured ovarian carcinoma cell lines infected with influenza A/PR8/34 were administered intraperitoneally (IP) to 40 patients with advanced ovarian carcinoma, including 31 with late-onset ascites and 5 with pleural effusions. PR8 virus-specific antigens and ovarian tumor-associated antigens have been demonstrated on two oncolysates designated OVO1 and OVO2. Thirty-five patients received 9 mg of a 1:1 mixture of OVO1 and OVO2, 5 patients received one or the other. During the first month three IP schedules were evaluated, i.e., single, biweekly, and weekly, which were followed by monthly injections. Intrapleural (IP1) injections of a 3.0-mg 1:1 mixture of OV1 and OV2 were administered to 3 patients concurrently with initial IP injections and to 2 patients following later development of pleural effusions. In 7 patients ascites disappeared; in 5 of these the number of cytologically detected malignant cells was markedly reduced, in 1 pleural effusion disappeared, and in 3 tumor masses were reduced. Tumor masses shrank also in 2 patients without ascites. Tumor reduction conformed to standard response criteria in 2 of the 5 patients. Response duration in the 9 responding patients lasted from 3 to 19 months and survival durations 4 to 42 months. Disease symptoms in 7 patients improved noticeably. Two of the 9 responders later developed unilateral pleural effusions that responded for 7 and 15+ months to a single IP1 injection. Seventeen patients experienced one or more treatment side effects including fever, nausea or anorexia, malaise, abdominal pain, and arthralgia, but in only 2 patients, both on the weekly schedule, was toxicity severe enough to require treatment withdrawal. Humoral responses to viral and tumor cell-surface antigens were frequently observed in patients demonstrating clinical activity.


Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found as an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and has diuretic, vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. The anti-inflammatory effects of emodin have been exhibited in various in vitro as well as in vivo models of inflammation including pancreatitis, arthritis, asthma, atherosclerosis and glomerulonephritis. As an anti-cancer agent, emodin has been shown to suppress the growth of various tumor cell lines including hepatocellular carcinoma, pancreatic, breast, colorectal, leukemia, and lung cancers. Emodin is a pleiotropic molecule capable of interacting with several major molecular targets including NF-κB, casein kinase II, HER2/neu, HIF-1α, AKT/mTOR, STAT3, CXCR4, topoisomerase II, p53, p21, and androgen receptors which are involved in inflammation and cancer. This review summarizes reported anti-inflammatory and anti-cancer effects of emodin, and re-emphasizes its potential therapeutic role in the treatment of inflammatory diseases and cancer.


Microbial pathogenesis in inflammatory bowel diseases.
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal system. Previously, it is considered the disease of the western world but now the incidence and prevalence of IBD are increasing globally with urbanization and modernization. Additionally, the major problem is the highest incidence of IBD among children and adolescents. The precise etiology of IBD is unknown and there is no cure for IBD, which is also the reason for increasing the number of cases worldwide. The IBD is a complex interplay of environment, immune system, and microbiota in a genetically susceptible host. Among these factors, the alteration in intestinal microbiota has been detected in IBD patients. The bacterial species associated with IBD include Mycobacterium paratuberculosis, adherent-invasive E. coli (AIEC), Helicobacter pylori, and Campylobacter concisus. Moreover, the efficacy of antibiotics and probiotics further suggests the role of microbes in IBD. However, no study confirmed the bacterial species as a cause of IBD as per Koch's postulates. Thus, still controversies exist regarding the role of microbes in IBD. Therefore, this paper aims to review the current literature to evaluate the role of microbes in IBD that would be a useful inventory of researchers working in this area.


Clustering of chronic kidney disease and cardiovascular risk factors in South-West Nigeria.
There exists a synergy between chronic kidney disease (CKD) and cardiovascular risk factors (CVRFs) with increased morbidity and poor outcomes. Data relating to this clustering in black homogenous populations is scanty. We aim to investigate this relationship in Nigerian communities. It was a cross-sectional observation study from semi-urban communities in South-West Nigeria. We used modified World Health Organization (WHO) questionnaire on chronic diseases (WHO STEPS) to gather information on socio-demographic data, biophysical and clinical characteristics. Biochemical analysis of plasma samples was done. We analyzed data of 1084 with mean age of 56.3 ± 19.9 years (33.4% female). Prevalence of stage 3 CKD was 14.2% (3a and 3b were 10.3% and 3% respectively). Prevalence of hypertension (systolic and diastolic blood pressure) and low high-density lipoprotein cholesterol (HDL-C) increased as clustering of cardiovascular (CV) risk factors (CVFRs) increased both in CKD and proteinuria (P < 0.05). CKD prevalence increases with number of risk factors. There was an inverse relationship between increasing risk factors and mean estimated glomerular filtration rate (eGFR) (P < 0.05). Clustering at least 2 CVRFs in the population with CKD compared to those without CKD was significantly higher (76.6% vs. 65.1%, OR: 1.8, 95% CI: 1.2-2.6, P = 0.005). Similarly, in a univariate analysis, albuminuria had an increased odds of clustering (69.7% vs. 59.6%, OR: 1.9, 95% CI 0.6-6.2, P = 0.409). Using multivariate logistic analysis, there is significantly increased odds of clustering when eGFR is <45 mL/min/1.73 m2 (OR: 2.66, 95% CI: 1.12-6.32) and microalbuminuria 1.74 (95% CI: 1.10-2.75). Reduced kidney function and proteinuria significantly clustered with CVRFs. This data suggests that individuals with CV clusters should be screened for CKD or vice versa and they should be considered for prompt management of their CVRFs.


Using an Early Warning Score for Nurse Shift Patient Handover: Before-and-after Study.
This study aimed to examine the impact of using an early warning score for shift patient handover on nurse and patient outcomes. A before-and-after study was conducted with nurses and patients in three general wards in a tertiary teaching hospital. A short-time nurse education on the National Early Warning Score 2 and the use of a checklist for score calculation were performed from June 4, 2019 to June 30, 2019. Outcomes of nurse response (safety competency, handover quality, teamwork, safety climate, and documentation of vital signs and clinical concerns), patient response (deterioration occurrence postadmission, hospitalization length, and discharge status), and adverse events (mortality, cardiopulmonary arrest, and unplanned intensive care unit admission) were measured using questionnaires and medical record reviews. Data from 89 nurses and 388 patients were analyzed. Regarding nurse outcomes, handover quality (p < .001), teamwork (p = .004), safety climate (p = .018), and recordings of vital signs (p = .047) and clinical concerns (p = .008) increased after early warning score use. However, no significant change in the safety competency scores was observed. Regarding patient outcomes, there were no significant changes in the occurrence of deterioration, hospitalization length, discharge status, and occurrence of adverse events between preintervention and postintervention. Despite no significant changes in patient outcomes, using a simple, evidence-based early warning score for patient handover enhanced socio-cultural factors for patient safety, with improved patient monitoring. The findings provide evidence that supports the active implementation of an early warning score to improve patient safety.


A Naringin-loaded gelatin-microsphere/nano-hydroxyapatite/silk fibroin composite scaffold promoted healing of critical-size vertebral defects in ovariectomised rat.
In this study, we investigated the effect of three-dimensional of naringin/gelatin microspheres/nano-hydroxyapatite/silk fibroin (NG/GMs/nHA/SF) scaffolds on repair of a critical-size bone defect of lumbar 6 in osteoporotic rats. In this work, a cell-free scaffold for bone-tissue engineering based on a silk fibroin (SF)/nano-hydroxyapatite (nHA) scaffold was developed. The scaffold was fabricated by lyophilization. Naringin (NG) was loaded into gelatin microspheres (GMs), which were encapsulated in the nHA/SF scaffolds. The materials were characterized using x ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. Moreover, the biomechanics, degradation, and drug-release profile of the scaffold were also evaluated. In vitro, the effect of the scaffold on the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was evaluated. In vivo, at 3 months after ovariectomy, a critical-size lumbar defect was indued in the rats to evaluate scaffold therapeutic potential. A 3-mm defect in L6 developed in 60 SD rats, which were randomly divided into SF scaffold, nHA/SF scaffold, NG/nHA/SF scaffold, NG/GMs/nHA/SF scaffold, and blank groups (n = 12 each). At 4, 8, 12, and 16 weeks postoperatively, osteogenesis was evaluated by X-ray, micro-computed tomography, hematoxylin-eosin staining, and fast green staining, and by analysis of BMP-2, Runx2, and Ocn protein levels at 16 weeks. In our results, NG/GM/nHA/SF scaffolds exhibited good biocompatibility, biomechanical strength, and promoted BMSC adhesion, proliferation, and calcium nodule formation in vitro. Moreover, NG/GMs/nHA/SF scaffolds showed greater osteogenic differentiation potential than the other scaffolds in vitro. In vivo, gradual new bone formation was observed, and bone defects recovered by 16 weeks in the experimental group. In the blank group, limited bone formation was observed, and the bone defect was obvious. In conclusion, NG/GMs/nHA/SF scaffolds promoted repair of a lumbar 6 defect in osteoporotic rats. Therefore, the NG/GMs/nHA/SF biocomposite scaffold has potential as a bone-defect-filling biomaterial for bone regeneration.


AeWRKY32 from okra regulates anthocyanin accumulation and cold tolerance in Arabidopsis.
Okra (Abelmoschus esculentus L.) is a tropical crop species, and its growth and development are severely affected by cold stress. Recent studies have identified a potential association between WRKY transcription factors and the cold response mechanism of crops. In this study, the AeWRKY32 transcription factor that encodes 482 amino acids was amplified from A. esculentus, and its expression level was found to be the highest in the okra flower. AeWRKY32 localized to the nucleus and displayed transcriptional activation capability. Under normal conditions, overexpression of AeWRKY32 induced anthocyanin accumulation, with higher expression levels of AtCHS1, AtCHI4, AtF3H1, and AtDFR2 in transgenic Arabidopsis. Under cold stress, anthocyanin levels were further elevated in transgenic Arabidopsis plants. At the same time, AeWRKY32 overexpression promoted ABA biosynthesis, inhibited H2O2 and O2- generation, induced stomatal closure, reduced electrolyte leakage, and thus improved the cold resistance of transgenic Arabidopsis. Furthermore, under cold stress, the expression profiles of AtCOR413, AtCOR15B, AtCBF1, and AtCBF2 were upregulated in transgenic Arabidopsis. Overall, our study provides evidence that AeWRKY32 serves as a crucial regulator in both anthocyanin accumulation and cold tolerance of transgenic Arabidopsis. Our findings could provide insights into the molecular mechanism linking AeWRKYs to plant cold tolerance.


Concanavalin A binding sites on the luminal surface of ependymal cells of third ventricle.
Detection of the Concanavalin A binding sites within the luminal surface of ependymal cells of the third ventricle has been accomplished using perfusion techniques as a way of exposing the cells to reaction solutions. Parameters for this procedure were established. It was found that electron dense reaction products form a layer ranging from 25--40 nm in thickness on the luminal surface of investigated cells. The microvilli exhibited a slightly thiner layer, the reaction products formed small patches on cilia.


[Calcium channel blockade and anti-free-radical actions of panaxadiol saponins Rb1, Rb2, Rb3, Rc, and Rd].
To identify the calcium channel blockade and anti-free-radical actions of panaxadiol saponins Rb1, Rb2, Rb3, Rc, and Rd. On ventricular myocardiocytes of Wistar rats, single channel activities of L, T, and B type Ca2+ channels were recorded with the cell-attached configuration of patch-clamp technic, and free radical contents were measured with electron spin resenance method. Rb1, Rb2, Rb3, and Rc 200 mumol.L-1 shortened the open times, prolonged the close times, and reduced the openstate probabilities of calcium channels and 30 mumol.L-1 antagonized the increase of free radical content induced by xanthine 0.42 mmol.L-1-xanthine oxidase 5.3 nmol.L-1, but Rd in the same dose behaved none of the effects. Rb1, Rb2, Rb3, and Rc had both the calcium channel blockade and anti-free-radical actions.


Prognostic Implications of Right Ventricular Function and Pulmonary Pressures Assessed by Echocardiography in Hospitalized Patients with COVID-19.
Pulmonary involvement in Coronavirus disease 2019 (COVID-19) may affect right ventricular (RV) function and pulmonary pressures. The prognostic value of tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (PAPS), and TAPSE/PAPS ratios have been poorly investigated in this clinical setting. This is a multicenter Italian study, including consecutive patients hospitalized for COVID-19. In-hospital mortality and pulmonary embolism (PE) were identified as the primary and secondary outcome measures, respectively. The study included 227 (16.1%) subjects (mean age 68 ± 13 years); intensive care unit (ICU) admission was reported in 32.2%. At competing risk analysis, after stratifying the population into tertiles, according to TAPSE, PAPS, and TAPSE/PAPS ratio values, patients in the lower TAPSE and TAPSE/PAPS tertiles, as well as those in the higher PAPS tertiles, showed a significantly higher incidence of death vs. the probability to be discharged during the hospitalization. At univariable logistic regression analysis, TAPSE, PAPS, and TAPSE/PAPS were significantly associated with a higher risk of death and PE, both in patients who were and were not admitted to ICU. At adjusted multivariable regression analysis, TAPSE, PAPS, and TAPSE/PAPS resulted in independently associated risk of in-hospital death (TAPSE: OR 0.85, CI 0.74-0.97; PAPS: OR 1.08, CI 1.03-1.13; TAPSE/PAPS: OR 0.02, CI 0.02 × 10-1-0.2) and PE (TAPSE: OR 0.7, CI 0.6-0.82; PAPS: OR 1.1, CI 1.05-1.14; TAPSE/PAPS: OR 0.02 × 10-1, CI 0.01 × 10-2-0.04). Echocardiographic evidence of RV systolic dysfunction, increased PAPS, and poor RV-arterial coupling may help to identify COVID-19 patients at higher risk of mortality and PE during hospitalization.


RNA-Sequencing Reveals Gene Expression and Pathway Signatures in Umbilical Cord Blood Affected by Birth Delivery Mode.
Cesarean section (CS) confers increased risk of type I diabetes, asthma, inflammatory bowel disease, celiac disease, overweight and obesity, etc., in the offspring. However, the underlying mechanism remains unknown. To investigate the influence of CS on gene expression in cord blood, we have performed RNA-sequencing followed by single-gene analysis, gene set enrichment analysis, gene co-expression network analysis, and interacting genes/proteins analysis in eight full-term infants born by elective CS and eight matched vaginally delivered (VD) infants. Crucial genes identified above were further validated in another 20 CS and 20 VD infants. We found for the first time that mRNA expression of genes involved in immune response (IL12A, INFG, IL1B, TNF, MIF, IL4, CA1, IFI27, HLA-DOB and EPHB1) and metabolism (DLK1, CYP2A6 and GATM) were significantly influenced by CS. Notably, serum TNF-α and IFN-γ were remarkably up-regulated in the CS infants (p = 5.0 × 10-4 and 3.0 × 10-3, respectively) compared to the VD infants. It is biologically plausible that CS may exert adverse impacts on offspring health through influencing expression of genes in the above processes. These findings will help understand the potential underlying mechanisms of the adverse health impacts of CS and identify biomarkers for future health of offspring born with different delivery modes. The online version contains supplementary material available at 10.1007/s43657-022-00086-7.


Overall survival benefits of first-line EGFR tyrosine kinase inhibitors in EGFR-mutated non-small-cell lung cancers: a systematic review and meta-analysis.
Accumulating data shows that exon 19 deletions and L858R, both activating epidermal growth factor receptor mutations in non-small-cell lung cancers (NSCLCs), are just two different entities in terms of prognosis and treatment response to tyrosine kinase inhibitors (TKIs). A systematic review and meta-analysis of randomized controlled trials comparing TKIs with conventional chemotherapy was performed. Eight trials of 1498 patients and five trials of 1279 patients with either exon 19 deletions or L858R were included in the meta-analysis. TKI treatment demonstrated progression-free survival benefit in patients with exon 19 deletions (hazard ratio (HR): 0.27, 95% confidence interval (CI): 0.21-0.35) and L858R (HR: 0.45, 95% CI: 0.35-0.58). Patients with exon 19 deletions had significant overall survival (OS) benefit under TKI treatment (HR: 0.72, 95% CI: 0.60-0.88). Subgroup analyses showed that irreversible TKIs, but not reversible TKIs, had statistically significant OS benefit in these patients (irreversible TKIs, HR: 0.59, 95% CI: 0.47-0.73; reversible TKIs, HR: 0.84, 95% CI: 0.69-1.02). Patients with L858R demonstrated no OS benefit under first-line TKI use (HR: 1.15, 95% CI: 0.95-1.39). In patients with advanced NSCLC harbouring exon 19 deletions, TKIs are associated with better OS compared with conventional chemotherapy. Future clinical trials should take exon 19 deletions and L858R as distinct disease entities and evaluate the treatment efficacy separately.


Understanding coronary artery disease patients' decisions regarding the use of chelation therapy for coronary artery disease: descriptive decision modeling.
A considerable number of patients receive chelation therapy to treat their coronary artery disease. However, there is no current empirical evidence to support its use. To better understand patient's decision-making processes regarding the use of chelation therapy as a treatment for coronary artery disease. Based on qualitative interviews with 32 coronary artery disease patients, a taxonomy of decision-related issues, hierarchical decision-model, and survey based on the model were developed. The model was then pilot tested with another group of 30 patients and revised accordingly. The final model was tested with another group of 167 patients (27 current users, 72 previous users, and 68 never users of chelation therapy). The primary examination of the model was to determine the degree to which it successfully identified people who fell within each behavioral group. This was done by dividing the total number of successes by the total number of cases on all paths (or questions in the questionnaire). The most important elements in the decision to use or not use chelation therapy were: previous experience with or learning about chelation therapy, openness to alternative treatments, satisfaction with current level of (traditional) care, physician opinion regarding chelation therapy, costs associated with chelation therapy, perceived access to chelation therapy provider, current state of health (good or bad), and wanting to do 'all one can' for heart health. When tested, the ability of the model to predict the appropriate outcome was nearly 93%. The most salient junctures in the model that led participants to different behavioral outcomes were: considering using non-traditional treatments; perceptions regarding potential risks and benefits; cost; and believing that using chelation therapy was 'doing all that they can' to help their heart health. Descriptive decision-modeling is a useful method to depict cardiac patients' decision-making concerning the use of chelation therapy. It can also assist healthcare providers and policy makers in directing interventions and policy aimed at enhancing the use of evidence-based therapies for cardiac patients.


DEPTOR is an in vivo tumor suppressor that inhibits prostate tumorigenesis via the inactivation of mTORC1/2 signals.
The DEPTOR-mTORC1/2 axis has been shown to play an important, but a context dependent role in the regulation of proliferation and the survival of various cancer cells in cell culture settings. The in vivo role of DEPTOR in tumorigenesis remains elusive. Here we showed that the levels of both DEPTOR protein and mRNA were substantially decreased in human prostate cancer tissues, which positively correlated with disease progression. DEPTOR depletion accelerated proliferation and survival, migration, and invasion in human prostate cancer cells. Mechanistically, DEPTOR depletion not only activated both mTORC1 and mTORC2 signals to promote cell proliferation and survival, but also induced an AKT-dependent epithelial-mesenchymal transition (EMT) and β-catenin nuclear translocation to promote cell migration and invasion. Abrogation of mTOR or AKT activation rescued the biological consequences of DEPTOR depletion. Importantly, in a Deptor-KO mouse model, Deptor knockout accelerated prostate tumorigenesis triggered by Pten loss via the activation of mTOR signaling. Collectively, our study demonstrates that DEPTOR is a tumor suppressor in the prostate, and its depletion promotes tumorigenesis via the activation of mTORC1 and mTORC2 signals. Thus, DEPTOR reactivation via a variety of means would have therapeutic potential for the treatment of prostate cancer.


Predicted health care profile after transition to adult care in Turner syndrome children-experience of single center.
Turner Syndrome (TS) is caused by the complete or partial loss of one of the X chromosomes in all or some female cell lines. The variable genotypes are responsible for a large phenotypic diversity, nevertheless most studies emphasize a weak correlation between genotype and phenotype. The study aimed to assess the occurrence of defects and diseases depending on the karyotype in patients with TS and correlation with the predicted health care profile after the transition to adulthood. 45 patients of the Department of Endocrinology and Pediatrics of the Medical University of Warsaw in 1990-2002 were analyzed. Girls were divided into 2 subgroups: "A", which included 16 patients with the karyotype 45,X, and "B", which included 29 girls with mosaic karyotypes. Based on the literature data, characteristic phenotypic features and the typical defects or diseases accompanying TS were selected, and the frequency of their occurrence was compared in both subgroups. Accordingly to this data, the predicted medical care profile was determined. In our study, patients with complete monosomy of the X chromosome had more characteristic phenotypic features. They needed sex hormone replacement therapy more often and started to menstruate spontaneously much less frequently (only 18.18% in monosomy vs. 73.91% in mosaic patients, p = 0.006). In patients with monosomy, congenital defects of the circulatory system were found more often (46.67% vs. 30.77%). The diagnosis in patients with mosaic karyotype was more often delayed, therefore the optimal time of growth hormone therapy was shorter. In our study, the X isochromosome determined the higher prevalence of autoimmune thyroiditis (83.33% vs. 12.5%, p = 0.049). We didn't find a correlation between the type of karyotype and health care profile after the transition, most of the patients needed more than 2 specialists. Most often, they required: gynecologists, cardiologists, and orthopedics. After the transition from pediatric to adulthood, patients with TS need multidisciplinary care, but not all need the same kind of assistance. The phenotype and comorbidities determine the profile of patients' health care, however it wasn't directly related to the type of karyotype in our study.


A genetic analysis of the photosynthetic properties of populations of Danthonia spicata that have different growth responses to light level.
Three populations of the grass Danthonia spicata were observed to have different rates of biomass accumulation when grown in common environment treatments. The populations were native to adjacent sites of different successional age and different levels of shading. Twelve individuals from each population were clonally replicated and two replicates were grown in each of two light treatments, 100% and 22% of unshaded sunlight. Following growth in the treatments the populations all exhibited the same mean light-saturated photosynthetic rate of 11.7 μmol m-2s-1. This rate is intermediate for published values of sun and shade species and for species from along a successional gradient. There was no difference in photosynthetic rate among treatments. There was significant genetic variation for lightsaturated photosynthetic rate within populations but no significant differences among populations. The populations had similar leaf water potential values of-1.12 MPa in all treatments. There were significant differences among treatments and genotypes for specific leaf weight which resulted in significant differences among treatments and no significant differences among genotypes in light-saturated photosynthetic rate expressed on a leaf weight basis. Lightsaturated photosynthetic rate had a high heritability and low plasticity. We postulate that photosynthetic rate is under strong selection and that the observed rates permit populations of D. spicata to grow in a wide range of habitat light levels.


Triggered Golgi membrane enrichment promotes PtdIns(4,5)P2 generation for plasma membrane repair.
The maintenance of plasma membrane integrity and a capacity for efficiently repairing damaged membranes are essential for cell survival. Large-scale wounding depletes various membrane components at the wound sites, including phosphatidylinositols, yet little is known about how phosphatidylinositols are generated after depletion. Here, working with our in vivo C. elegans epidermal cell wounding model, we discovered phosphatidylinositol 4-phosphate (PtdIns4P) accumulation and local phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] generation at the wound site. We found that PtdIns(4,5)P2 generation depends on the delivery of PtdIns4P, PI4K, and PI4P 5-kinase PPK-1. In addition, we show that wounding triggers enrichment of the Golgi membrane to the wound site, and that is required for membrane repair. Moreover, genetic and pharmacological inhibitor experiments support that the Golgi membrane provides the PtdIns4P for PtdIns(4,5)P2 generation at the wounds. Our findings demonstrate how the Golgi apparatus facilitates membrane repair in response to wounding and offers a valuable perspective on cellular survival mechanisms upon mechanical stress in a physiological context.


Bivalvular mechanical mitral-aortic valve replacement in 254 patients: long-term results--a 22-year follow-up.
We have retrospectively studied 254 patients who underwent a bivalvular mechanical mitral-aortic replacement in the cardiovascular and thoracic surgery unit of Nantes from 1979 to 1989. The follow-up was 22 years (1979 to 2001). The last patient was operated on 12 years before the end of the follow-up. All mitral prostheses were St. Jude Medical (SJM) bileaflet valves, and the aortic prostheses were 124 monodisc Björk-Shiley valves, 3 Sorin prostheses, and 127 St. Jude Medical bileaflet prostheses. The mean age was 56.8 +/- 8.5 years with a sex ratio equal to 1. Rheumatism as the etiology predominated with 79.5%. Ninety-seven percent of the patients were followed for a total of 2,779 patient-years and a mean of 11.7 years. Operative mortality was 7.08%. Freedom from overall mortality and valve-related mortality at 22 years were 45.7% +/- 3.6% and 73.1% +/- 3%, respectively. The linearized rates of thromboembolic and hemorrhagic events were 1.07% and 0.9% per patient-year, respectively. Multivariate analysis showed age (p < 0.002), sex (p < 0.01), and degenerative etiology (p = 0.04) as independent factors of late mortality, and age, sex, degenerative disease, and tricuspid pathology were related to valve-related mortality. This study shows good results after mechanical mitral-aortic replacement in terms of survival rate and quality of life in surviving patients, and outlines the factors influencing long-term results as compared with isolated mitral valve replacement.


Bacteroides humanifaecis sp. nov., isolated from faeces of healthy Korean.
Two obligately anaerobic, Gram-stain-negative, non-motile, non-spore-forming and short rod shaped bacteria, designated KGMB07931T and KGMB10229, were isolated from faeces of two Korean persons. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains KGMB07931T and KGMB10229 were very similar to each other (99.9%) and grouped within the genus Bacteroides, displaying the highest similarity with Bacteroides uniformis ATCC 8492T (97.5%), Bacteroides rodentium JCM 16496T (96.6%), and Bacteroides fluxus YIT 12057T (94.5%). Both strains grew optimally at 37 °C and pH 7.5 in the presence of 0.5% (w/v) NaCl. The complete genome of KGMB07931T comprises 3,335 protein-coding genes with a total of 4,240,638 bp and an average G + C content of 46.3 mol%. The major fatty acids were C18:1 cis9, anteiso-C15:0, iso-C15:0, and Summed Feature 11 (iso-C17:0 3OH and/or C18:2 DMA); the predominant respiratory quinones were MK-9 and MK-10; the major fermentation end products were acetate and isobutyrate. The genome of strain KGMB07931T encoded the starch utilization system (Sus) operon, susABCDEFG, suggesting that this strain uses many complex polysaccharides that cannot be digested by humans. Based on polyphasic taxonomic data, strains KGMB07931T and KGMB10229 represent a novel species within the genus Bacteroides, for which the name Bacteroides humanifaecis sp. nov. is proposed. The type strain is KGMB07931T (= KCTC 25160T = NBRC 115005T).


Awareness of and preference for disease prognosis and participation in treatment decisions among advanced cancer patients in Myanmar: Results from the APPROACH study.
To investigate prognostic awareness, preference for prognostic information, and perceived and preferred roles in decision making among patients with advanced cancer in Myanmar. A cross-sectional survey was administered at the Yangon General Hospital to stage 4 cancer patients who were at least 21 years old and aware of their cancer diagnosis. Patients were asked questions about their prognosis, participation in treatment decisions, sociodemographic and clinical information. Data from 131 patients were analyzed using descriptive statistics and logistic regressions. Only 15% of patients surveyed were aware that their cancer was advanced and only a quarter (26%) of patients knew that treatment intent was noncurative. The likelihood of treatment-intent awareness was higher among patients who were male, high income, and aware that they had advanced cancer. Roughly 60% of patients reported playing an active or collaborative role in treatment decisions, with a strong preference (59%) for the latter. For the majority of patients (69%), perceived and preferred roles in decision making were the same. Sociodemographic characteristics did not predict perceived and preferred roles in decision making. This is the first effort to analyze prognostic awareness and decision-making practices among advanced cancer patients in Myanmar. Patients had inadequate knowledge on their disease progression and intent of treatment. Yet, the majority of them were keen to be involved in treatment decisions.


Dentin infiltration ability of different classes of adhesive systems.
This study evaluates the dentin infiltration ability of various types of adhesives and compares four classes of adhesive systems with regard to this property. The infiltration is determined quantitatively, characterized as tag length and ratio of infiltration, and qualitatively, characterized as homogeneity, regularity, and continuity of the resin tags. Flat dentin surfaces from 140 halves of caries-free molars were bonded with four classes of adhesive systems. The adhesives (n = 20) were labeled with rhodamine B isothiocyanate and applied on the occlusal dentin following the manufacturer's recommendations and were subsequently light cured, 20 s. Then a 2-mm thick composite layer was applied and light cured, 20 s. The specimens were stored in distilled water at 37°C, 24 h. Two slices were sectioned mesio-distally from each sample and were investigated with a confocal laser scanning microscope. The measurements were done at 0.5, 1.5, and 2.5 mm from the enamel-dentin junction. The data were analyzed by using analysis of variance and the general linear model. The class of adhesive, the composition, and the dentin position were significant factors affecting the investigated parameters. The use of etch and rinse adhesives in comparison to self-etch adhesives provided the formation of longer, more homogeneous, very regularly distributed but mostly fractured tags. A comparison of adhesives confirmed that etch and rinse systems remain better in bond infiltration. While the importance of tags formation on bonding is still controversially discussed, adhesive systems with a high ratio of infiltration might better protect the tooth against microorganism contamination.


Comparison of postoperative outcomes in ulcerative colitis and familial polyposis patients after ileoanal pouch operations.
Pouchitis is a poorly understood inflammatory condition that occurs in the ileal pouches of patients who have undergone the ileal-pouch anal anastomosis after restorative proctocolectomy. This postoperative condition is much more common in patients with ulcerative colitis (UC) than familial adenomatous polyposis (FAP) colitis. It has been suggested that, owing to pouchitis, UC patients do not attain the same quality of life that FAP patients do after the ileal-pouch anal anastomosis operation. We hypothesized that health-related quality of life does not differ between FAP and UC patients. We analyzed the postoperative morbidity and gastrointestinal function in 110 consecutive patients having undergone the ileal-pouch anal anastomosis for either UC or FAP at OU Medical Center from 1983 to 2000 by retrospective record review. Health-related quality of life was assessed in 83 patients using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and the Medical Outcome Study Short-Form 36 (SF-36) questionnaire. With the exception of pouchitis, there was no difference in perioperative outcome, morbidity, or functional status between UC and FAP patients. The SIBDQ and SF-36 revealed no statistically significant difference between FAP and UC patients. As expected, UC patients are more likely to develop pouchitis. Despite this, our data reveal that both patient groups enjoy a similarly good functional status and quality of life.


[Emergency treatment: coronal restoration with pulpal-dentinal protection. Splints].
The authors, explain the need of a pulpo-dentinal protection, and present the way to adopt in case of dental traumas, as well for hard tissues (coronal and radicular) and for non calcified tissues (luxations). This protection allows a cicatrisation of dento-periodontal tissues.


Neurourological Management After Failed Intradetrusor OnabotulinumtoxinA Injections.
There are more questions than answers in the explanation for failure of onabotulinumtoxinA injection. We need to define what criteria should be used to diagnose it, what local bladder, neurological, or possibly immune phenomena are responsible for it, and the best and safest way to proceed in these vulnerable patients. We propose a management algorithm that may be worth testing at each step in clinical trials.


Characteristics of Doppler embolic signals observed following carotid endarterectomy.
Postoperative Doppler embolic signals following carotid endarterectomy (CEA) are associated with an increased risk of stroke, but the characteristics of these signals are rarely reported. In this study, we survey signals from 1485 emboli, assumed to consist predominantly of thrombus. Data were obtained by monitoring the middle cerebral arteries of 100 consecutive CEA patients during postoperative recovery. The distribution of embolic signal frequencies, intensities and durations revealed that embolic signals do not occur randomly in the sonogram. In particular, we find that the signals possess a characteristic distribution of velocities reflecting the preferred path of the embolus through the artery (at approximately 75% of the distance between the centre of the artery and the artery wall). Embolic signals were more likely to be observed at cardiac cycle positions between 35% and 80% from the start of systole than elsewhere. After eliminating other considerations, we hypothesized that this peak in the distribution of signals in the sonogram arose due to the localization of emboli trajectories and a strong tendency for emboli to detach from the carotid bifurcation during systole.


Maresin conjugates in tissue regeneration-1 suppresses ferroptosis in septic acute kidney injury.
Ferroptosis is unique among different types of regulated cell death and closely related to organ injury. Whether ferroptosis occurs in sepsis-associated acute kidney injury (SA-AKI) is not clear. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is crucial to the regulation of ferroptosis. We and others have shown that Maresin conjugates in tissue regeneration 1 (MCTR1) or other members of specialized pro-resolving mediators (SPMs) can actively regulate inflammation resolution and protect organs against injury in inflammatory diseases by activating the Nrf2 signaling. The aim of this study was to determine whether ferroptosis occurs in SA-AKI. Furthermore, we investigated the potential role and mechanism of MCTR1 in the regulation of ferroptosis in SA-AKI, which mainly focus on the Nrf2 signaling. We demonstrated for the first time that ferroptosis is present in SA-AKI. Moreover, MCTR1 effectively suppressed ferroptosis in SA-AKI. Meanwhile, MCTR1 upregulated the expression of Nrf2 in the kidney of septic mice. Nrf2 inhibitor ML-385 reversed MCTR1-regulated ferroptosis and AKI, implying that Nrf2 is involved in the inhibitory effects of MCTR1 on ferroptosis in SA-AKI. Further, MCTR1 inhibited ferroptosis and elevated the expression of Nrf2 in LPS-induced HK-2 cells. However, Nrf2 siRNA offset the effect of MCTR1 on ferroptosis. Finally, we observed that MCTR1 ameliorates multi-organ injury and improves survival in animal models of sepsis. These data demonstrate that MCTR1 suppresses ferroptosis in SA-AKI through the Nrf2 signaling. Our study enriches the pathophysiological mechanism of SA-AKI and provides new therapeutic ideas and potential intervention targets for SA-AKI.


[In vitro tests for the reduction of high norepinephrine, barbiturate and bromide concentrations in blood by hemofiltration (author's transl)].
In vitro tests have shown that a treatment of blood according to the principle of hemofiltration is suitable both for the normalisation of excessive norepinephrine plasma level, e.g. following severe burns, and also for the elimination of toxic quantities of barbiturate and bromide resulting from poisoning by sedatives.


Multilabel immunofluorescence and antigen reprobing on formalin-fixed paraffin-embedded sections: novel applications for precision pathology diagnosis.
We report new methods for multilabel immunofluorescence (MIF) and reprobing of antigen epitopes on the same formalin-fixed paraffin-embedded (FFPE) sections. The MIF method includes an antigen-retrieval step followed by multilabel immunostaining and examination by confocal microscopy. As examples, we illustrate epitopes localized to the apical and basolateral membranes, and the cytoplasm of enterocytes of normal small intestine and in cases of congenital enteropathies (microvillous inclusion disease and congenital tufting enteropathy). We also demonstrate localization of the bile salt excretion pump protein (BSEP) in bile canalicular membrane of normal hepatocytes and in cases of primary sclerosing cholangitis. To demonstrate colocalization of cytoplasmic and nuclear epitopes we analyzed normal control and hyperplastic pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEBs), presumed airway sensors in the lungs of infants with bronchopulmonary dysplasia (BPD). As cytoplasmic markers we used anti-bombesin or anti-synaptic vesicle protein 2 (SV2) antibody, respectively, and for nuclear localization, antibodies against neurogenic genes mammalian achaete-scute homolog (Mash1) and prospero homeobox 1 (Prox1), essential for NEB cells differentiation and maturation, hypoxia-inducible factor 1α (HIF1α) a downstream modulator of hypoxia response and a proliferation marker Ki67. The reprobing method consisted of removal of the previously immunolabeled target and immunostaining with different antibodies, facilitating colocalization of enterocyte brush border epitopes as well as HIF1α, Mash1 and Prox1 in PNEC/NEB PNEC and NEBs. As these methods are suitable for routine FFPE pathology samples from various tissues, allowing visualization of multiple epitopes in the same cells/sections with superior contrast and resolution, they are suitable for a wide range of applications in diagnostic pathology and may be particularly well suited for precision medicine diagnostics.


Properties of a defined mutant of Escherichia coli thymidylate synthase.
A mutant of Escherichia coli thymidylate synthase (F3-TS), resulting from the replacement of a tyrosine for a cysteine 50 amino acids from the amino-terminal end, has been purified to homogeneity and found to contain less than 0.2% of the activity of the native enzyme (thyA-TS). Although this protein formed a ternary complex with 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5,10-methylenetetrahydrofolate, like the native enzyme, the extent of complex formation was significantly impaired as determined by equilibrium dialysis and circular dichroism. Thus, unlike the native enzyme, where 2 mol of FdUMP were present in each mole of ternary complex, F3-TS contained less than 1 mol of FdUMP/mol of ternary complex. Similarly, the binding of dUMP by F3-TS was greatly diminished relative to thyA-TS, but its binding as well as that of FdUMP could be improved by the presence of either the folate substrate or a tight binding folate analogue, 10-propargyl-5,8-dideazafolate (PDDF). However, despite the fact that PDDF enhanced the binding of FdUMP and dUMP to F3-TS, the binding of PDDF to the mutant enzyme was also greatly impaired. This contrasts with the native enzyme, which, under the same conditions, bound about 2 mol of PDDF/mol of enzyme in the presence or absence of either FdUMP or dUMP. Circular dichroism analyses with PDDF in the presence of dUMP or FdUMP yielded analogous results, but the effects were less dramatic than those obtained by equilibrium dialysis. Evidence in support of a structural difference between thyA-TS and F3-TS was obtained by demonstrating that the latter protein was 15-fold slower in forming a ternary complex with dUMP and PDDF than the former and that the mutant enzyme was less stable than the native enzyme.


Molecular and Neuroendocrine Mechanisms of Avian Seasonal Reproduction.
Animals living outside tropical zones experience seasonal changes in the environment and accordingly, adapt their physiology and behavior in reproduction, molting, and migration. Subtropical birds are excellent models for the study of seasonal reproduction because of their rapid and dramatic response to changes in photoperiod. For example, testicular weight typically changes by more than a 100-fold. In birds, the eyes are not necessary for seasonal reproduction, and light is instead perceived by deep brain photoreceptors. Functional genomic analysis has revealed that long day (LD)-induced thyrotropin from the pars tuberalis of the pituitary gland causes local thyroid hormone (TH) activation within the mediobasal hypothalamus. This local bioactive TH, triiodothyronine (T3), appears to regulate seasonal gonadotropin-releasing hormone (GnRH) secretion through morphological changes in neuro-glial interactions. GnRH, in turn, stimulates gonadotropin secretion and hence, gonadal development under LD conditions. In marked contrast, low temperatures accelerate short day (SD)-induced testicular regression in winter. Interestingly, low temperatures increase circulating levels of T3 to support adaptive thermogenesis, but this induction of T3 also triggers the apoptosis of germ cells by activating genes involved in metamorphosis. This apparent contradiction in the role of TH has recently been clarified. Central activation of TH during spring results in testicular growth, while peripheral activation of TH during winter regulates adaptive thermogenesis and testicular regression.


Preoperative Depression and Anxiety Impact on Inpatient Surgery Outcomes: A Prospective Cohort Study.
To determine the association of preoperative mood symptoms and postoperative adverse outcomes; to explore sex-specific differences. Depression and anxiety can increase postoperative mortality. Psychological stress is associated with a chronic inflammatory response unfavorable to postsurgical healing. Prospective cohort study. Patients were recruited from surgical preadmission clinics at a university hospital. Preoperative depression and anxiety were measured via the Beck Depression and Beck Anxiety Inventories (BDI-II and BAI). Our primary outcome was a composite of postoperative complications, extended length of stay (ELOS) and early readmission. Associated variables included demographics, preoperative pain, pain tolerance/catastrophizing, coping mechanisms, postoperative pain, and opioid use. We adjusted for age, comorbidities, and surgical specialty. Of 1061 recruited patients (ten surgical specialties, 2015-2020), 455 males and 486 females had preoperative and postoperative data available. Mean age was 62.9 (range 20.2-96.2). At baseline, 9.3% of patients had moderate or severe depression; 7.4% had moderate or severe anxiety. Females were more likely to be moderately or severely depressed (11% vs 7%, P = 0.036) and moderately or severely anxious (9% vs 6%, P = 0.034). Females had significantly fewer reported comorbidities and lower American Society of Anesthesiologists category (P < 0.001). Increasing BDI-II and BAI scores significantly increased likelihood of postoperative complications, ELOS, and/or hospital readmission in females (adjusted odds ratio [aOR] = 2.57 for BDI-II 1-19 vs 0, P = 0.041; aOR = 4.48 for BDI-II > 19 vs 0, P = 0.008; aOR = 1.54 for BAI ≤ 6 vs >6, P = 0.038) but not in males. Mood symptoms did not influence postoperative pain or opioid use. Preoperative depression and anxiety negatively impact surgical outcomes in female patients undergoing major surgery.


Use of public data to describe COVID-19 contact tracing in Hubei Province and non-Hubei provinces in China between 20 January and 29 February 2020.
Contact tracing has been used in China and several other countries in the WHO Western Pacific Region as part of the COVID-19 response. We describe COVID-19 cases and the number of contacts traced and quarantined per case as part of COVID-19 emergency public health response activities in China. We abstracted publicly available, online aggregated data published in daily COVID-19 situational reports by China's National Health Commission and provincial health commissions between 20 January and 29 February 2020. The number of new contacts traced by report date was computed as the difference between total contacts traced in consecutive reports. A proxy for the number of contacts traced per case was computed as the number of new contacts traced divided by the number of new cases. During the study period, China reported 80 968 new COVID-19 cases and 659 899 contacts. In Hubei Province, there were 67 608 cases and 264 878 contacts, representing 83% and 40% of the total, respectively. Non-Hubei provinces reported tracing 1.5 times more contacts than Hubei Province; the weekly number of contacts traced per case was also higher in non-Hubei provinces than in Hubei Province and increased from 17.2 in epidemiological week 4 to 115.7 in epidemiological week 9. More contacts per case were reported from areas and periods with lower COVID-19 case counts. With other non-pharmaceutical interventions used in China, contact tracing and quarantining large numbers of potentially infected contacts probably contributed to reducing SARS-CoV-2 transmission.


Poly(3-Hydroxybutyrate) Production in Repeated fed-Batch with Cell Recycle Using a Medium with low Carbon Source Concentration.
Among approaches applied to obtain high productivity and low production costs in bioprocesses are high cell density and the use of low cost substrates. Usually low cost substrates, as waste/agroindustrial residues, have low carbon concentration, which leads to a difficulty in operating bioprocesses. Real time control of process for intracellular products is also difficult. The present study proposes a strategy of repeated fed-batch with cell recycle to attain high cell density of Cupriavidus necator and high poly(3-hydroxybutyrate) (P(3HB)) productivity, using a substrate with low carbon source concentration (90 g l(-1)). Also, the use of the oxygen uptake rate data was pointed out as an on line solution for process control, once P(3HB) is an intracellular product. The results showed that total biomass (X), residual biomass (Xr) and P(3HB) values at the end of the culture were 61.6 g l(-1), 19.3 g l(-1) and 42.4 g l(-1) respectively, equivalent to 68.8 % of P(3HB) in the cells, and P(3HB) productivity of 1.0 g l(-1) h(-1). Therefore, the strategy proposed was efficient to achieve high productivity and high polymer content from a medium with low carbon source concentration.


Bone marrow stromal cells inhibits HMGB1-mediated inflammation after stroke in type 2 diabetic rats.
High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of pro-inflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats. Injection of bone marrow stromal cells (BMSCs) into type 2 diabetic rats significantly reduced the expression of HMGB1 and RAGE, attenuated BBB leakage, and improved functional outcome after stroke. BMSCs-treated type 2 diabetic rats inhibited inflammation and improved functional outcome after stroke. Furthermore, in vitro data support the hypothesis that BMSCs-induced reduction of HMGB1 and RAGE in T2DM-MCAo rats contributed to attenuated inflammatory response in the ischemic brain, which may lead to the beneficial effects of BMSCs treatment. Further investigation of BMSCs treatment in type 2 diabetic stroke is warranted.


GABA receptor alterations after chronic lithium administration. Comparison with carbamazepine and sodium valproate.
1. Effects of lithium, carbamazepine, sodium valproate and baclofen on GABA receptors were examined in several regions of the rat brain. 2. [3H]Muscimol (MUS) and [3H] (-)baclofen (BAC) were used to label GABAA and GABAB receptors, respectively, in synaptic membranes from rat brain. 3. Single treatment with lithium chloride, carbamazepine or sodium valproate did not change [3H]MUS or [3H]BAC binding in the frontal cortex, hippocampus and thalamus. 4. Following chronic treatment with lithium, carbamazepine or sodium valproate, [3H]BAC binding was significantly increased in the hippocampus but not in the frontal cortex, thalamus or striatum. 5. [3H]Muscimol binding did not change in any region examined after chronic treatment with lithium, carbamazepine or sodium valproate. 6. Single and chronic administration of baclofen did not change [3H]MUS or [3H]BAC binding. 7. One common mechanism of action of mood stabilizers may be mediated by GABAB receptors in the hippocampus.


Spatiotemporal mode-locking in multimode fiber lasers.
A laser is based on the electromagnetic modes of its resonator, which provides the feedback required for oscillation. Enormous progress has been made toward controlling the interactions of longitudinal modes in lasers with a single transverse mode. For example, the field of ultrafast science has been built on lasers that lock many longitudinal modes together to form ultrashort light pulses. However, coherent superposition of longitudinal and transverse modes in a laser has received little attention. We show that modal and chromatic dispersions in fiber lasers can be counteracted by strong spatial and spectral filtering. This allows locking of multiple transverse and longitudinal modes to create ultrashort pulses with a variety of spatiotemporal profiles. Multimode fiber lasers thus open new directions in studies of nonlinear wave propagation and capabilities for applications.


Potential anatomic substrate of peri-atrioventricular nodal atrial tachycardia ablated from the noncoronary sinus of Valsalva.
Although focal atrial tachycardia (AT) is known to sometimes be ablated from the noncoronary aortic cusp (NCC), the electro-anatomic characteristics of NCC-AT are not well known. We compared the clinical, 12-lead electrocardiogram (ECG), and transthoracic echocardiogram characteristics of 6 women (median age, 66.5 years) with NCC-AT and 12 age-matched women (median age, 64.0 years) with atrioventricular nodal reentrant tachycardia (AVNRT) as the control group. There was no difference in the prevalence of hypertension between the two groups (67 vs. 33 %, respectively, P = 0.3213). The resting ECG of the NCC-AT group vs. that of the AVNRT group showed a significantly longer PQ interval (170.0 (interquartile range (IQR), 157.5-180.0 ms) vs. 140.0 ms (IQR, 122.5-147.5 ms), P = 0.0010) and leftward shifting of the QRS axis (4° (IQR, -26.0° to 24.0°) vs. 57° (IQR, 43.0-70.2°), P = 0.0087). The upper interventricular septum (IVS) thickness was significantly greater (15.6 (IQR, 11.9-18.7 ms) vs. 11.7 mm (IQR, 10.2-12.9 ms), P = 0.0393), and the angle formed by the aortic roof and IVS (AS angle) was significantly steeper (103.0° (IQR, 94.2-119.2°) vs. 122.5° (IQR, 108.5-128.5°), P = 0.0343) in the NCC-AT group than in the AVNRT group. Our data suggest that NCC-AT is characterized by a longer atrioventricular (AV) conduction time, steeper AS angle, and thicker IVS than are seen with AVNRT. These electrocardiographic and echocardiographic characteristics from the IVS to the peri-AV nodal regions may have some effect on the development of NCC-AT.


Characteristics of patients with vaginal rupture and evisceration.
To characterize vaginal rupture and evisceration. We reviewed medical records (1970-2001) for use of the diagnostic terms "vaginal rupture," "vaginal evisceration," and "ruptured enterocele." Twelve clinical cases were identified. Patients usually presented with pain, vaginal bleeding, and abdominal pressure. In 9 of 12 women, rupture was primarily associated with postmenopausal prolapse and a history of pelvic surgery. Women with a history of abdominal hysterectomy tended to rupture through the vaginal cuff, and those with a history of vaginal hysterectomy tended to rupture through a posterior enterocele. Premenopausal rupture in 1 woman occurred postcoitally and involved the posterior fornix. Prolapse recurrence after repair was limited to 1 woman. Vaginal rupture and evisceration should be considered in women presenting with acute vaginal bleeding and pelvic pain. Evaluation is especially important in postmenopausal women with a history of pelvic surgery. In some cases, surveillance after pelvic surgery may prevent rupture, evisceration, and incarceration. II-3


Percutaneous insertion of double-J ureteral stent in children with ureteral obstruction: our experiences.
Ureteral obstruction (UO) is usually treated by surgical or endoscopic approaches. We investigated whether percutaneous anterograde treatment with insertion of double-J ureteral stent (DJ) is a feasible alternative technique for the management of UO in selected cases, where traditional approaches are not possible or too risky. The DJ was percutaneously inserted into 10 children (mean age 9 years) who suffered from UO. Three children had already been treated surgically for complex urotract congenital anomalies; six children had restenosis/reocclusion or stenosis of ureteropelvic junction; and one girl suffered migration of an intraoperatively placed DJ with stenosis of the distal ureter. Percutaneous insertion of the DJ was successful on the first attempt in 8 and on the second in 2 children. Adverse events after the procedure, all successfully treated, included one pyelonephritis and one migration of DJ, and 3 children had bacteriuria and 3 hematuria. Mean duration of insertion of the DJ was 6.4 months. After removal of the DJ, 7 children did not need any further interventions, but 2 children needed surgical correction and 1 reinsertion of the DJ. In selected cases, percutanous insertion of a DJ should be considered as an alternative to surgery or endoscopic treatment in the management of children with UO.


Correction: Lysosomal sequestration of hydrophobic weak base chemotherapeutics triggers lysosomal biogenesis and lysosome-dependent cancer multidrug resistance.
[This corrects the article DOI: 10.18632/oncotarget.2732.].


Comparison of two immunoradiometric assays for parathyroid hormone-related protein in the evaluation of cancer patients with and without hypercalcemia.
Hypercalcemia is a common paraneoplastic syndrome due to the secretion by tumors of parathyroid hormone-related protein (PTHrP) and/or other osteolytic factors. In the present study, we have measured plasma PTHrP using two immunoradiometric assays for PTHrP, assay N (Nichols) and assay I (INCSTAR), recognizing the 1-86 domain of PTHrP, for the evaluation of malignancy-associated hypercalcemia. The study included 25 tumor patients with hypercalcemia (HCa) [corrected serum calcium (SCa) > or = 2.70 mmol/L], 20 normocalcemic patients with cancer (NCa), and ten healthy control subjects. Plasma PTHrP was either undetectable or within the respective normal range in the majority of NCa patients and in the control subjects, with both assays. Plasma PTHrP was increased in 13 and 15 of HCa cases with assay N and assay I, respectively. PTHrP was elevated in plasma in 5/6 (assay N) and 3/6 (assay I) HCa patients with squamous tumors. However, plasma PTHrP was high in only 2/9 (assay N) and 1/9 (assay I) HCa cases with hematological tumors. Less than 40% of HCa patients with bone metastases, and >75% of those without bone involvement, had elevated plasma PTHrP with both assays. Detectable plasma PTHrP and SCa were significantly correlated using assay N (p = 0.025) and assay I (p = 0.01), in the HCa group. A highly significant correlation (p <0.001) was found between detectable plasma PTHrP with both assays, and a high agreement between them based on simple kappa statistics (p < 0.001), in the latter group. Our results indicate that each assay may be similarly useful in detecting PTHrP hyperproduction in cancer patients.


Longterm azithromycin therapy for three patients with chronic lower respiratory tract infections.
Longterm macrolide therapy has been reported to be effective in treating chronic lower respiratory tract infections (CLRTIs). In this context, erythromycin and clarithromycin are usually used for this purpose. However, refractory cases are occasionally encountered, thereby indicating a major problem pending. In the present study, we administered azithromycin to three patients with CLRTIs whose clinical course had been unsatisfactory with longterm therapy of either erythromycin or clarithromycin. Following longterm therapy with azithromycin, both the incidence of acute exacerbations and the sputum volume were decreased. A significant change in the sputum flora was observed, without obvious side effects; however, no improvement was evidenced in the findings on flow volume curve tests and arterial blood gas analysis. In advanced disease, longterm azithromycin therapy may be as effective as that with erythromycin or clarithromycin; in our view, however, its efficacy may be limited, and large-scale clinical trials are required to determine the most suitable macrolide for the treatment of CLRTIs.


Acoustic performance of near-rail low-height noise barriers installed on suburban railway bridges.
With the large-scale construction of suburban railway viaducts, the noise problem along the viaducts is becoming more and more prominent. Conventional vertical noise barriers have been widely used to alleviate the noise problem along the suburban railway viaducts. However, conventional vertical noise barriers often have an adverse effect on the urban landscape and also block the view of train drivers and passengers. A type of near-rail low-height noise barrier was planned to install on the viaducts of Wenzhou Rail Transit Line S1 to reduce the impact of noise on residents along the railway lines. To assess the acoustic performance of the near-rail low-height noise barrier, a numerical procedure for railway viaduct comprehensive noise considering wheel-rail noise and structure-borne noise of the bridge and noise barriers was proposed and then verified by a field test. On this basis, numerical models were established to compare the acoustic performances of the near-rail low-height noise barrier and conventional vertical noise barrier. The influences of the height and top shape of the near-rail low-height noise barrier on the acoustic performance were discussed. Based on the numerical analysis results, it is found that both the near-rail low-height noise barrier and conventional vertical noise barrier have good acoustic performances. The noise reduction effect of the near-rail low-height noise barrier is slightly better than that of the conventional vertical noise barrier. The acoustic performance of the near-rail low-height noise barrier gradually improves, but the improvement rate gradually slows down as the height of the noise barrier increases. The noise reduction effects of both the inverted L-shaped and Y-shaped near-rail low-height noise barrier are obviously better than that of the vertical one, while the noise reduction effects of the inverted L-shaped near-rail low-height noise barrier are slightly better than the Y-shaped one.


Sensitivity enhancement of integrated optical sensors by use of thin high-index films.
The proportion of power carried in the superstrate medium by the guided modes of integrated optical waveguides can be increased by the addition of a thin high-index film. Enhanced refractive-index sensing is demonstrated with channel waveguide Mach-Zehnder interferometers with Ta(2)O(5) overlays. Sensitivity increases by a factor greater than 50, and a detection limit better than 5 x 10(-7) is obtained. This approach is broadly applicable to sensing at waveguide surfaces where the strength of evanescent fields dictates performance.


Using Mechanical Turk for research on cancer survivors.
The successful recruitment and study of cancer survivors within psycho-oncology research can be challenging, time-consuming, and expensive, particularly for key subgroups such as young adult cancer survivors. Online crowdsourcing platforms offer a potential solution that has not yet been investigated with regard to cancer populations. The current study assessed the presence of cancer survivors on Amazon's Mechanical Turk (MTurk) and the feasibility of using MTurk as an efficient, cost-effective, and reliable psycho-oncology recruitment and research platform. During a <4-month period, cancer survivors living in the United States were recruited on MTurk to complete two assessments, spaced 1 week apart, relating to psychosocial and cancer-related functioning. The reliability and validity of responses were investigated. Within a <4-month period, 464 self-identified cancer survivors on MTurk consented to and completed an online assessment. The vast majority (79.09%) provided reliable and valid study data according to multiple indices. The sample was highly diverse in terms of U.S. geography, socioeconomic status, and cancer type, and reflected a particularly strong presence of distressed and young adult cancer survivors (median age = 36 years). A majority of participants (58.19%) responded to a second survey sent one week later. Online crowdsourcing represents a feasible, efficient, and cost-effective recruitment and research platform for cancer survivors, particularly for young adult cancer survivors and those with significant distress. We discuss remaining challenges and future recommendations. Copyright © 2016 John Wiley & Sons, Ltd.


[Cloning of β-actin Gene in Psammosilene tunicoides and Its Role as a Reference Gene].
To establish a real-time quantitative PCR method to detect Psammosilene tunicoides β-actin, and to provide a reference gene for the detection of Psammosilene tunicoides genes by q PCR. Specific primers were designed based on the conserved region of the β-actin gene( Gen Bank) and were used to amplify β-actin by PCR. β-actin was also used as a reference gene in the q PCR analysis of glycosyltransferase gene( UGT) expression in the roots,stems,and leaves of Psammosilene tunicoides. The length of the β-actin gene amplicon from Psammosilene tunicoides was 153 bp and shared relatively high homology with β-actin found in Vaccaria segetalis, Myosoton aquaticum and Portulaca oleracea. Furthermore, UGT was revealed to be stably expressed in different Psammosilene tunicoides tissues when β-actin was employed as the reference gene. β-actin is a reliable and suitable reference gene for studies on the expression of triterpenoid saponin biosynthesis-related genes in Psammosilene tunicoides.


A real-time three-dimensional echocardiographic quantitative analysis of left atrial function in left ventricular diastolic dysfunction.
The evaluation of left ventricular diastolic function provides important information about hemodynamics and has prognostic implications for various cardiac diseases. In particular, left atrial (LA) volume is an increasingly significant prognostic biomarker for diastolic dysfunction. The aim of this study was to assess left ventricular diastolic function by measuring changes in LA volume using real-time 3-dimensional echocardiography. The 106 subjects were divided into 4 groups (normal, impaired relaxation, pseudonormal, and restrictive) on the basis of diastolic function, as assessed by transmitral flow patterns. LA volume was measured during a heart cycle using real-time 3-dimensional echocardiography. LA stroke volume (maximum LA volume - minimum LA volume) and the LA ejection fraction (LA stroke volume/maximum LA volume x 100) were calculated using Doppler imaging to assess their correlation with other parameters used to evaluate left ventricular diastolic function, including transmitral flow pattern and early diastolic mitral annular velocity (E'). LA volume indexed to body surface area was dilated in subjects with left ventricular diastolic dysfunction, whereas the LA ejection fraction was lower. The maximum LA volume, minimum LA volume, and LA ejection fraction were significantly different between each group, and each was significantly correlated with the ratio of early diastolic transmitral flow velocity (E) to E' (E/E'). The LA ejection fraction correlated best with E/E' (r = -0.68, p <0.0001). In conclusion, cyclic changes in LA volume could be measured using real-time 3-dimensional echocardiography, and measuring LA function with this method may be a viable alternative for the accurate assessment of left ventricular diastolic function.


Phlebotomus sergenti parrot, 1917: morphological and isoenzymatic comparisons of two natural populations from Tenerife (Canary Islands, Spain) and Crete (Greece).
Samples of two Phlebotomus sergenti natural populations from San Juan (Tenerife), representing the western edge of the distribution area of this species, and Axos (Crete) were collected. The morphological comparison showed marked differences in the lengths of parts of the male genitalia, female pharynx, and spermathecae. The isoenzyme study revealed characteristic monomorphic phenotypes for glucose phosphate isomerase, hexokinase, and phosphoglucomutase in the Canarian specimens as compared with the Cretan population. These results confirm the heterogeneity of P. sergenti and indicate the utility of a systematic double approach for a revision of this taxon.


Subepithelial fibroblasts in intestinal villi: roles in intercellular communication.
Ingestion of food and water induces chemical and mechanical signals that trigger peristaltic reflexes in the gut. Intestinal villi are motile, equipped with chemosensors and mechanosensors, and transduce signaling to sensory neurons, but the exact mechanisms have not yet been elucidated. Subepithelial fibroblasts located under the villous epithelium form contractile cellular networks via gap junctions. The networks ensheathe lamina propria and are in close contact with epithelium, neural and capillary networks, smooth muscles, and immune cells. Unique characteristics of subepithelial fibroblasts have been revealed by primary cultures isolated from rat duodenal villi. They include rapid reversal changes in cell shape by cAMP reagents and endothelins, cell shape-dependent mechanosensitivity that induces ATP release as a paracrine mediator, contractile ability, and expression of various receptors for vasoactive and neuroactive substances. Herein, we review these characteristics that play a key role in the villi. They serve as a barrier/sieve, flexible mechanical frame, mechanosensor, and signal transduction machinery in the intestinal villi, which are regulated locally and dynamically by rapid cell shape conversion.


Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease.
Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.


H3S10 phosphorylation-mediated transcriptional regulation by Aurora kinase A.
Histone H3S10 phosphorylation has been known as a cell cycle-specific marker and has a role in transcriptional activation. Various kinases phosphorylate H3S10 in different species, however, the role of the mitotic serine/threonine protein kinase Aurora A (AURKA) is largely unknown. Here we present evidence that AURKA phosphorylates H3S10 and activates target gene transcription. We show that down-regulation of AURKA level during leukemia cell differentiation results in decreased H3S10 phosphorylation level. We further show that AURKA is recruited to target gene promoters and activates transcription via H3S10 phosphorylation. Furthermore, this recruitment can be disrupted by the AURKA inhibitor Alisertib and results in H3K9-me2 recruitment by G9a.


The body balance training effect on improvement of motor functions in paretic extremities in patients after stroke. A randomized, single blinded trial.
Study evaluates movement selectivity improvement in hemiparetic post-stroke patients after balance training. Study included 26 patients and 15 healthy subjects (control group C). Patients were divided into two groups with 20-day balance training (A) and without (B). Normal standing weight distribution was expressed in percentages, center of feet pressure (COP) sway velocities were evaluated in anterior-posterior and medio-lateral (Y, X) directions for normal standing with eyes open and closed (EO, EC) and for tandem. Brunnström scale assessed movement selectivity. Weight distribution dissymmetry (Δ10%) was found. It was reduced (Δ2%) after training in group A. COP were higher for X direction (±6mm/s vs ±12mm/s) in normal standing. Difference (±12mm/s) was found for Y in tandem. Brunnström score increased in group A from 0.3 to 0.6. It was negatively correlated with average COP for EO and EC in Y and X and for tandem in X. Training reduces weight-bearing dissymmetry and improves movement selectivity.


Retraction Note: Theoretical Limits of Energy Density in Silicon-Carbon Composite Anode Based Lithium Ion Batteries.
This article has been retracted.


Lysine deserts prevent adventitious ubiquitylation of ubiquitin-proteasome components.
In terms of its relative frequency, lysine is a common amino acid in the human proteome. However, by bioinformatics we find hundreds of proteins that contain long and evolutionarily conserved stretches completely devoid of lysine residues. These so-called lysine deserts show a high prevalence in intrinsically disordered proteins with known or predicted functions within the ubiquitin-proteasome system (UPS), including many E3 ubiquitin-protein ligases and UBL domain proteasome substrate shuttles, such as BAG6, RAD23A, UBQLN1 and UBQLN2. We show that introduction of lysine residues into the deserts leads to a striking increase in ubiquitylation of some of these proteins. In case of BAG6, we show that ubiquitylation is catalyzed by the E3 RNF126, while RAD23A is ubiquitylated by E6AP. Despite the elevated ubiquitylation, mutant RAD23A appears stable, but displays a partial loss of function phenotype in fission yeast. In case of UBQLN1 and BAG6, introducing lysine leads to a reduced abundance due to proteasomal degradation of the proteins. For UBQLN1 we show that arginine residues within the lysine depleted region are critical for its ability to form cytosolic speckles/inclusions. We propose that selective pressure to avoid lysine residues may be a common evolutionary mechanism to prevent unwarranted ubiquitylation and/or perhaps other lysine post-translational modifications. This may be particularly relevant for UPS components as they closely and frequently encounter the ubiquitylation machinery and are thus more susceptible to nonspecific ubiquitylation.


Transformation of waste cooking oil into C-18 fatty acids using a novel lipase produced by Penicillium chrysogenum through solid state fermentation.
The prime aim of the current work was to illustrate the components existing in repeatedly used cooking oil and to develop an economical process for the production of fatty acids from low cost feedstock waste. The waste cooking oil was characterized by the occurrence of high molecular weight hydrocarbons and polymerized derivative of esters. Triacontanoic acid methyl ester, 2,3,5,8-Tetramethyldecane, 3,3 dimethyl heptane, and 2,2,3,3-teramethyl pentane were detected as thermal and oxidative contaminants that adversely affect the quality of cooking oil. Fundamentally, waste cooking oil comprises ester bonds of long chain fatty acids. The extracellular lipase produced from P. chrysogenum was explored for the hydrolysis of waste cooking oil. The incorporation of lipase to waste cooking oil in 1:1 proportion released 17 % oleic acid and 5 % stearic acid.


The effects of physical exercise on structural, functional, and biochemical brain characteristics in individuals with chronic whiplash-associated disorder: A pilot randomized clinical trial.
Exercise for people with whiplash associated disorder (WAD) induces hypoalgesic effects in some, but hyperalgesic effects in others. We investigated the exercise-induced neurobiological effects of aerobic and strengthening exercise in individuals with chronic WAD. Sixteen participants (8 WAD, 8 pain-free [CON]) were randomised to either aerobic or strengthening exercise. MRI for brain morphometry, functional MRI for brain connectivity, and magnetic resonance spectroscopy for brain biochemistry, were used at baseline and after the 8-week intervention. There were no differences in brain changes between exercise groups in either the WAD or CON group, therefore aerobic and strengthening data were combined to optimise sample size. After the exercise intervention, the CON group demonstrated increased cortical thickness (left parahippocampus: mean difference = 0.04, 95% CI = 0.07-0.00, p = 0.032; and left lateral orbital frontal cortex: mean difference = 0.03, 95% CI = 0.00-0.06, p = 0.048). The WAD group demonstrated an increase in prefrontal cortex (right medial orbital frontal) volume (mean difference = 95.57, 95% CI = 2.30-192.84, p = 0.046). Functional changes from baseline to follow-up between the default mode network and the insula, cingulate cortex, temporal lobe, and somatosensory and motor cortices, were found in the CON group, but not in the WAD group. There were no changes post-exercise in brain biochemistry. Aerobic and strengthening exercises did not exert differential effects on brain characteristics, however differences in structural and functional changes were found between WAD and CON groups. This suggests that an altered central pain modulatory response may be responsible for differential effects of exercise in individuals with chronic WAD.


Linear regression model for predicting interactive mixture toxicity of pesticide and ionic liquid.
The nature of most environmental contaminants comes from chemical mixtures rather than from individual chemicals. Most of the existed mixture models are only valid for non-interactive mixture toxicity. Therefore, we built two simple linear regression-based concentration addition (LCA) and independent action (LIA) models that aim to predict the combined toxicities of the interactive mixture. The LCA model was built between the negative log-transformation of experimental and expected effect concentrations of concentration addition (CA), while the LIA model was developed between the negative log-transformation of experimental and expected effect concentrations of independent action (IA). Twenty-four mixtures of pesticide and ionic liquid were used to evaluate the predictive abilities of LCA and LIA models. The models correlated well with the observed responses of the 24 binary mixtures. The values of the coefficient of determination (R (2)) and leave-one-out (LOO) cross-validated correlation coefficient (Q(2)) for LCA and LIA models are larger than 0.99, which indicates high predictive powers of the models. The results showed that the developed LCA and LIA models allow for accurately predicting the mixture toxicities of synergism, additive effect, and antagonism. The proposed LCA and LIA models may serve as a useful tool in ecotoxicological assessment.


Idiopathic dystonia: neuropharmacological study.
A total of 15 patients affected by idiopathic dystonia (7 with generalized and 8 with focal or segmental dystonia) were subjected to therapy with bromocriptine at low doses, pimozide and trihexyphenidyl. The symptoms were evaluated by giving a progressive score in relation to the intensity of the dystonic symptom to each of the body segments involved by the dystonia. Bromocriptine did not significantly modify the dystonia. Pimozide showed a slight nonsignificant improvement of the dystonic symptoms. Trihexyphenidyl was effective in the generalized dystonias, in agreement with previous reports in the literature. The variation in the pharmacological results could be due to the diversity of the dystonic syndromes, which comprise cases that are different in age at onset, site of dystonic symptoms, and evolution.


Unilateral lesion of the nigroestriatal pathway with 6-OHDA induced allodynia and hyperalgesia reverted by pramipexol in rats.
Pain is the non-motor symptom with the highest prevalence in patients with Parkinson's Disease (PD) affecting 40-85%. This study aimed to investigate the development of tactile allodynia and mechanical hyperalgesia after the nigrostriatal dopaminergic lesion induced by the unilateral 6-hydroxydopamine (6-OHDA) injection at different doses in the substantia nigra pars compacta (SNpc). Moreover, we studied the possible antiallodynic and antihyperalgesic effect with the acute and the subacute treatment of the pramipexole (PPX) in rats. First, dopaminergic lesion was realized by the unilateral injection of 6-OHDA (6, 10 and 16 μg/μl) into the SNpc. To know the establishment of motor deficits, we measure several turns and forelimb-use asymmetry by rotational behavior and cylinder, respectively. On the other hand, to investigate allodynia and hyperalgesia induced by 6-OHDA, we used the von Frey filaments. Moreover, antiallodynic and antihyperalgesic effect induced by PPX (0.03, 0.3 and 3 mg/kg, s.c.) was examined on acute and subacute conditions. We found that major dopaminergic lesion with 16 μg/μl of 6-OHDA caused the highest allodynia and hyperalgesia effects in both paws, as well as the major motor deficits. In addition, the treatment with PPX at 0.3 mg/kg reverts the allodynia and the hyperalgesia induced by 6-OHDA. In conclusion, the dopaminergic lesion into SNpc induce allodynia and hyperalgesia in both paws; interestingly the treatment with PPX can be suggested as an analgesic drug for patients with PD.


Portrait of a rural health graduate: exploring alternative learning spaces.
Given that the staffing of rural facilities represents an international challenge, the support, training and development of students of rural origin at institutions of higher learning (IHLs) should be an integral dimension of health care provisioning. International studies have shown these students to be more likely than students of urban origin to return to work in rural areas. However, the crisis in formal school education in some countries, such as South Africa, means that rural students with the capacity to pursue careers in health care are least likely to access the necessary training at an IHL. In addition to challenges of access, throughput is relatively low at IHLs and is determined by a range of learning experiences. Insight into the storied educational experiences of health care professionals (HCPs) of rural origin has the potential to inform the training and development of rural-origin students. Six HCPs of rural origin were purposively selected. Using a narrative inquiry approach, data were generated from long interviews and a range of arts-based methods to create and reconstruct the storied narratives of the six participants. Codes, categories and themes were developed from the reconstructed stories. Reid's four-quadrant model of learning theory was used to focus on the learning experiences of one participant. Alternative learning spaces were identified, which were made available through particular social spaces outwith formal lecture rooms. These offered opportunities for collaboration and for the reconfiguring of the participants' agency to be, think and act differently. Through the practices enacted in particular learning spaces, relationships of caring, sharing, motivating and mentoring were formed, which contributed to personal, social, academic and professional development and success. Learning spaces outwith the formal lecture theatre are critical to the acquisition of good clinical skills and knowledge in the development of socially accountable HCPs of rural origin.


Changes in HIV-related behaviours over time and associations with rates of HIV-related services coverage among female sex workers in Sichuan, China.
To investigate changes in HIV-related behaviours among female sex workers (FSW) and associations with services coverage rates. Behavioural surveillance data from Sichuan, China, were analysed. A mapping exercise was conducted; FSW were recruited from randomly selected sex-work establishments in 19 sites in Sichuan, China, from 2003 (n = 7068), 2004 (n = 6875) and 2005 (n = 6833). Site variations were substantial. The random effect pooled AOR comparing the prevalence of condom use with regular sex partners, possession of condoms, HIV-related knowledge, HIV antibody testing and services coverage rates in 2005 versus 2003 ranged from 1.42 to 20.35. The 95% CI of these pooled AOR all excluded 1.0; hence rejecting the null hypothesis that such OR were not different from 1.0. Most of the AOR of these evaluative parameters (indicator of improvement) for the 19 individual sites in 2004 and 2005 (vs 2003) were significantly associated with coverage rates (Spearmen correlation coefficients = 0.35 to 0.67, p<0.05). Improvements were observed in relevant behaviours and coverage rates and the two were associated with each other.


Anorectal sensitivity and responses to rectal distention in patients with ulcerative colitis.
Anorectal function in ulcerative colitis was assessed by measuring pressures at multiple sites in the anus and rectum under basal conditions and during balloon distention of the rectum in 29 patients with ulcerative colitis (12 active, 11 quiescent, and 6 during both phases) and in 12 normal controls. Resting and squeeze sphincter pressures were similar in the three groups. The lowest rectal volume that could be perceived, the volume required to induce a desire to defecate, and the maximum tolerable rectal volume were all lower in patients with active colitis than in patients with quiescent colitis (p less than 0.001) and controls (p less than 0.001). The rectal volume required to cause a sustained anal relaxation was lower in patients with active colitis (p less than 0.05) than in controls. Both peak and steady state rectal pressures in response to rectal distention were significantly higher in patients with active colitis than in patients with quiescent colitis (p less than 0.05) and controls (p less than 0.02). Paired studies showed that during remission of disease there was a decrease in rectal sensitivity (p less than 0.05) and an increase in rectal compliance (p less than 0.05). These results suggest that the frequent and urgent defecation, i.e., the predominant feature of active colitis, is related to a hypersensitive and poorly compliant rectum, which, upon distention, is more reactive and is more likely to induce prolonged sphincter relaxation.


Glycine betaine modulates chromium (VI)-induced morpho-physiological and biochemical responses to mitigate chromium toxicity in chickpea (Cicer arietinum L.) cultivars.
Chromium (Cr) accumulation in crops reduces yield. Here, we grew two chickpea cultivars, Pusa 2085 (Cr-tolerant) and Pusa Green 112 (Cr-sensitive), in hydroponic and pot conditions under different Cr treatments: 0 and 120 µM Cr and 120 µM Cr + 100 mM glycine betaine (GB). For plants grown in the hydroponic media, we evaluated root morphological attributes and plasma membrane integrity via Evans blue uptake. We also estimated H+-ATPase activity in the roots and leaves of both cultivars. Plants in pots under conditions similar to those of the hydroponic setup were used to measure growth traits, oxidative stress, chlorophyll contents, enzymatic activities, proline levels, and nutrient elements at the seedling stage. Traits such as Cr uptake in different plant parts after 42 days and grain yield after 140 days of growth were also evaluated. In both cultivars, plant growth traits, chlorophyll contents, enzymatic activities, nutrient contents, and grain yield were significantly reduced under Cr stress, whereas oxidative stress and proline levels were increased compared to the control levels. Further, Cr uptake was remarkably decreased in the roots and leaves of Cr-tolerant than in Cr-sensitive cultivars. Application of GB led to improved root growth and morpho-physiological attributes and reduced oxidative stress along with reduced loss in plasma membrane integrity and subsequently increase in H+-ATPase activity. An increment in these parameters shows that the exogenous application of GB improves the Cr stress tolerance in chickpea plants.


The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria.
Drug resistance to first-line antimalarials-including artemisinin-is increasing, resulting in a critical need for the discovery of new agents with novel mechanisms of action. In collaboration with the Walter and Eliza Hall Institute and with funding from the Wellcome Trust, a phenotypic screen of Merck's aspartyl protease inhibitor library identified a series of plasmepsin X (PMX) hits that were more potent than chloroquine. Inspired by a PMX homology model, efforts to optimize the potency resulted in the discovery of leads that, in addition to potently inhibiting PMX, also inhibit another essential aspartic protease, plasmepsin IX (PMIX). Further potency and pharmacokinetic profile optimization efforts culminated in the discovery of WM382, a very potent dual PMIX/X inhibitor with robust in vivo efficacy at multiple stages of the malaria parasite life cycle and an excellent resistance profile.


Surface-enhanced Raman activity and stability study of silver films prepared by reduction of Ag+ ions in N,N-dimethylformamide.
A new SERS-active silver film prepared by directly depositing silver nanoparticles on glass is reported. The spontaneous reduction of Ag+ ions in N,N-dimethylformamide (DMF) (in the absence of a protecting agent) leads to the deposition of silver nanoparticles on clean glass surfaces in contact with the solution. The observed optical micrographs and AFM images show that the arrangement of the nanoparticles is inhomogeneous and the particles appear to be closely packed. These films are shown to be excellent substrates for SERS measurements, demonstrating significant enhancement, good stability, and trace detection capability. The SERS enhancement of the silver films with different deposition times was compared and found that the 8-h film gives the largest enhancement ability with an enhancement factor estimated at about 10(9). It is also found that the silver films stored for 80 days in air show no significant degradation in their sensitivity.


Ellagic acid attenuates testicular disruption in rheumatoid arthritis via targeting inflammatory signals, oxidative perturbations and apoptosis.
Reduced male fertility has been regarded as a serious complication of rheumatoid arthritis. Phytochemicals have been described as protective agents against rheumatoid arthritis-linked testicular impairment. The current study aimed to investigate the potential protective effects of ellagic acid on rheumatoid arthritis-evoked testicular dysfunction vis-à-vis the reference anti-inflammatory celecoxib. Ellagic acid (50 mg/kg/day) and celecoxib (5 mg/kg/day) were administered orally for 20 days in adjuvant-induced arthritic rats. Current data revealed that ellagic acid counteracted rheumatoid arthritis-evoked testicular histopathologic changes, disrupted sperm characteristics and low gonadosomatic index with comparable efficacy to celecoxib. Ellagic acid also enhanced the testicular steroidogenesis via upregulating the gene expression of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein with consequent boosting of serum testosterone. Notably, ellagic acid attenuated the testicular inflammatory responses through suppression of myeloperoxidase, tumor necrosis factor-α and cyclo-oxygenase-2 protein expression together with enhancing the anti-inflammatory signal interleukin 10. Ellagic acid also curbed the redox alterations via lowering the production of lipid peroxides and nitric oxide and elevation of the anti-oxidant reduced glutathione. In support of cell survival, ellagic acid combated testicular apoptosis through downregulating caspase-3 protein expression. The present work accentuates the beneficial actions of ellagic acid in rheumatoid arthritis-incurred testicular impairment and disrupted spermatogenesis via combating the inflammatory, oxidative and apoptotic aberrations.


Fractionated stereotactic radiotherapy of small intracranial malignancies.
To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.


Synergistic Wound Healing by Novel Ag@ZIF-8 Nanostructures.
In this paper, novel zeolitic imidazolate framework-8 (ZIF-8) functionalized with Ag (Ag@ZIF-8) nanoparticles were synthesized through a green, facile and environmental-friendly process for wound dressing applications. X-ray diffraction revealed that the ZIF-8 and Ag@ZIF-8 were successfully synthesized by green solvents at ambient temperature. Field-emission scanning electron microscopy indicated a homogeneous porous blend of ∼30 nm chitosan/bacterial cellulose (CS/BC) nanofibers embedded with ∼80-110 nm nanoparticles of the ZIF-8 and Ag@ZIF-8. Transmission electron microscopy revealed the Ag@ZIF-8 nanostructures consist of ZIF-8 cores that are covered by 5-20 nm Ag nanoparticles. MTT assay indicated excellent cell viability values of ∼115 and 109% for the CS/BC nanocomposites reinforced by ZIF-8 and Ag@ZIF-8 nanoparticles, respectively. The Ag-containing wound dressings showed 52-300% of effective antibacterial activities. Animal studies demonstrated excellent healing for the wound treated by CS/BC-25%Ag@ZIF-8 nanocomposite with ∼91% of wound closure after 14 days of treatment. Hematoxylin and eosin (H&E) staining revealed successful healing and tissue regeneration for the wounds treated using the CS/BC-Ag@ZIF-8 nanocomposites. This kind of nanocomposites with synergistic antimicrobial and bioactivity properties can be a promising candidate for regenerative medicine.


[Musculoskeletal disorders of the masticatory system. Consensus concerning diagnosis and therapy in gnathology].
Diagnosis and management of musculoskelatal disorders of the mandibular locomotor system have changed throughout the past decades. The Dutch Society of Temporomandibular Disorders and Prosthetic Dentistry initiated a consensus on this subject. The Utrecht Medical Center and the dental schools of the universities in Amsterdam, Groningen and Nijmegen produced a consensus statement, which eventually may lead to guidelines for the Dutch dental profession. The bi-axial somatic and phychosocial diagnostic approach is endorsed. Assessment, diagnostic subgroups, and management strategies, including occlusal appliances, physiotherapy, psychological treatment, and surgery are described. Counseling and reversible treatments are first choice options, although minimal invasive procedures may be considered in the early phase approach.