Efficacy and safety of rosuvastatin every other day compared with once daily in patients with hypercholesterolemia.
Although most patients with hypercholesterolemia require life-long therapy with statins, these drugs are underused due to high costs. Every-other-day therapy could be one strategy to resolve this problem. To compare the efficacy and safety of rosuvastatin 10 mg administered every other day versus once daily. An 8 week, randomized, open-label, parallel trial was conducted at the outpatient department of Phramongkutklao Hospital in Bangkok, Thailand. Eighty patients with primary hypercholesterolemia were equally randomized to receive rosuvastatin 10 mg once daily or every other day; 76 patients completed the study. Laboratory data were assessed at baseline and at the end of the study. Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 48% and 39% in the once-daily and every-other-day groups, respectively (p = 0.011). The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the once-daily (85%) and every-other-day (70%) groups (p = 0.180). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times baseline levels of aspartate aminotransferase or alanine aminotransferase or 10 times that of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of the once-daily (0.72 dollars) regimen was about 38% higher than that of the every-other-day (0.44 dollars) regimen. Every-other-day dosing of rosuvastatin may be an alternative regimen for cost savings, without a major decrease in therapeutic benefit or increase in adverse events, in patients with hypercholesterolemia. The number of patients achieving their LDL-C goal using the every-other-day regimen is comparable with the number using the once-daily regimen, especially in the low-risk patient category.


Novel Substituted Cyclopropyl Compounds as CFTR Modulators for Treating Cystic Fibrosis.
Provided herein are novel substituted cyclopropyl compounds as CFTR modulators, pharmaceutical compositions, use of such compounds in treating cystic fibrosis, and processes for preparing such compounds.


Principles of geriatric pharmacology.
Elderly patients are affected by multiple chronic age-related diseases. In prescribing drugs for them one should have sound knowledge of the physiological changes and social issues. Altered drug behaviour in the elderly is to be taken into account. Increasing age may alter absorption, distribution, metabolism or excretion of drugs which have been discussed in a nutshell. While prescribing drugs to the elderly one must be cautious in selection, right doses, proven efficacy, polypharmacy, cost factor and so on.


Protection by the flavonoids quercetin and luteolin against peroxide- or menadione-induced oxidative stress in MC3T3-E1 osteoblast cells.
Potential protective effects of the flavonoids quercetin and luteolin have been examined against the oxidative stress of MC3T3-E1 osteoblast-like cells. Although hydrogen peroxide and menadione reduced cell viability, the toxicity was prevented by desferrioxamine or catalase but not superoxide dismutase, suggesting the involvement of hydrogen peroxide in both cases. Quercetin and luteolin reduced the oxidative damage, especially that caused by hydrogen peroxide. When cultures were pre-incubated with quercetin or luteolin, protection was reduced or lost. Protection was also reduced when a 24 h pre-incubation with the flavonoids was followed by exposure to menadione alone. Pretreating cultures with luteolin impaired protection by quercetin, whereas quercetin pretreatment did not affect protection by luteolin. It is concluded that quercetin and luteolin suppress oxidative damage to MC3T3-E1 cells, especially caused by peroxide. The reduction in protection by pretreatment implies a down-regulation of part of the toxic transduction pathway.


XRCC3 T241M polymorphism and lung cancer risk in the Han Chinese population: a meta-analysis.
Numerous studies have evaluated the association between the X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphism and lung cancer risk; however, the actual association is controversial. We examined whether the T241M polymorphism confers a lung cancer risk in China. We searched the PubMed, Google Scholar, and China National Knowledge Infrastructure databases to identify studies that examined the association between the XRCC3 T241M polymorphism and the risk of lung cancer. We estimated the pooled odds ratio with its 95% confidence interval to assess this association. A total of 3977 patients with lung cancer and 3761 controls from 8 comparative studies were included in this meta-analysis. The meta-analysis results revealed no significant association between the XRCC3 T241M polymorphism and lung cancer risk. In the subgroup analysis, 6 studies with sample sizes over 500 found that the T241M polymorphism had no association with lung cancer. The XRCC3 T241M polymorphism may not be a risk factor for lung cancer. However, larger studies involving a stratified case-control population and biological characterization are needed to validate this finding.


Kinetics of immune cell migration at the human ocular surface.
The conjunctiva has a resident population of intraepithelial and stromal immune cells. These cells play an active part in ocular surface defence and disease. Our aim was to study the migration of immune cells in the human conjunctiva, across the basement membrane and to characterize their phenotypes. Organ cultures of human conjunctival samples, denuded of the epithelium, were maintained for varying time periods. Cells migrating on to the surface were harvested and analysed by flow cytometry. Conjunctival samples were also studied by immunohistology and electron microscopy. A preferential unidirectional migration of immune cells from the stroma, through pores in the basement membrane, towards the surface was noted. Cells migrated through intrastromal channels, communicating with the surface basement membrane pores. CD3+ T cells (76.18%) were the predominant migrating phenotype. The ratio of CD4:CD8 T cells was approximately 4:1 as compared with the control conjunctiva where the ratio was approximately 2:1. Various other phenotypes including NK, NKT and B cells were also detected. Only 8.41% of the migrating population expressed the Human mucosal lymphocyte-1 marker of intraepithelial lymphocytes. Immune cells migration at the ocular surface is an active process involving the formation of intrastromal channels, and cell egression through intact basement membrane pores. The preferential migration of CD4 T cells indicates that this is a specific response of conjunctival lymphoid tissue and not a passive movement of cells. A wide range of immune cell phenotypes exist at the ocular surface. This model can serve to test in vitro the effects of injurious agents on the ocular surface.


Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor (CTGF) in pathological fibrosis.
The cause of fibrotic disease is unknown. We have undertaken transcriptional profiling of dermal fibroblasts cultured from patients with the fibrotic disease scleroderma (systemic sclerosis, SSc) to identify genes overexpressed in fibrosis and have explored their contribution to the fibrotic phenotype. Connective tissue growth factor (CTGF, CCN2), a member of the CCN family of proteins, is overexpressed in SSc fibroblasts. In adult skin, CTGF is not normally expressed in dermal fibroblasts. However, CTGF is induced during the wound healing response and is constitutively overexpressed by fibroblasts present in fibrotic lesions. The overexpression of CTGF present in fibrotic lesions contributes to the phenotype of scleroderma in that CTGF promotes matrix deposition, and fibroblast adhesion and proliferation. In animal models, whereas either TGF beta or CTGF alone produce only a transient fibrotic response, CTGF and TGF beta act together to promote sustained fibrosis. Thus the constitutive overexpression of CTGF by fibroblasts present in fibrotic lesions would be expected to directly contribute to chronic, persistent fibrosis.


Transcripts within the replication origin, oriC, of Escherichia coli.
Transcription start and termination sites were mapped in the E. coli replication origin, oriC. Outward transcription from within oriC (promoters Pori-r and Pori-l) was found to start in vivo at position 178 for Pori-l and at positions 294 and 304 for Pori-r, respectively. These transcripts were terminated after 100-150 bases, at terminators designated Tori-l and Tori-r. Transcription from the 16 kd promoter, which lies clockwise adjacent to oriC and promotes transcription toward oriC, started at position 757 and gave transcripts with 3' ends at several positions within and to the left of the minimal replication origin. However, the majority of transcripts traversed the whole oriC region, and were not terminated within the DNA segment tested. Transcription of the chromosomal 16 kd gene was negatively regulated by DnaA protein and positively affected by dam methylation. The possible function of these transcripts is discussed.


Biomarkers of postharvest resilience: unveiling the role of abscisic acid in table grapes during cold storage.
Table grapes are considered non-climacteric fruit, not showing a rapid increase in respiration rate and ethylene production during ripening. Previous research has suggested that abscisic acid (ABA) may have a more crucial role in grape postharvest behaviour. This study aimed to identify biomarkers of postharvest resilience and flavour life of imported table grapes. An experiment was designed to determine i) the role of ABA and catabolites on grape berry senescence; ii) the spatial distribution of these hormones within the grape berry, and iii) the effect of 1-MCP and storage temperature on its postharvest quality. Hence, the use of an ethylene inhibitor, 1-methylcyclopropane (1-MCP), during table grape storage was investigated. Table grapes (Vitis vinifera L.) cv. 'Krissy' were subjected to i) control (untreated); and ii) 1-MCP (1 µL L-1; 12 hours; 15°C) and stored under two scenarios: i) 15 days at 0.5°C, followed by five days at 5.5°C to simulate shelf-life; and ii) 20 days at 5.5°C to simulate a higher storage temperature followed by shelf-life. Physiological (i.e. mould incidence, skin colour, firmness, respiration rate) and biochemical analysis (i.e. individual sugars, organic acids, abscisic acid and catabolites) were performed. Grapes subjected to 5.5°C showed significantly higher mould incidence at the end of the shelf-life compared to 0.5°C storage temperature (12.6% vs. 3.1%). Also, and for the first time, the spatial distribution of ABA during the senescence of table grapes was profiled; the distal section had three times more ABA and metabolites than the proximal. We demonstrated that senescence processes were initiated after a significant increase in respiration rate (from 1 to 2.8 mL CO2 kg-1 h-1), and that ABA could be considered a biomarker for table grapes senescence, since an ABA peak preceded the increase in respiration rate, mould incidence, organic acids, and sucrose hydrolysis during postharvest storage; and coincided with a decrease in berry firmness. These findings are of significant importance for the industry as understanding how ABA regulates both senescence processes and quality changes during postharvest cold storage of tables grapes can improve the consistency and reduce waste and consumer complaints.


Manifold Preserving: An Intrinsic Approach for Semisupervised Distance Metric Learning.
In this paper, we address the semisupervised distance metric learning problem and its applications in classification and image retrieval. First, we formulate a semisupervised distance metric learning model by considering the metric information of inner classes and interclasses. In this model, an adaptive parameter is designed to balance the inner metrics and intermetrics by using data structure. Second, we convert the model to a minimization problem whose variable is symmetric positive-definite matrix. Third, in implementation, we deduce an intrinsic steepest descent method, which assures that the metric matrix is strictly symmetric positive-definite at each iteration, with the manifold structure of the symmetric positive-definite matrix manifold. Finally, we test the proposed algorithm on conventional data sets, and compare it with other four representative methods. The numerical results validate that the proposed method significantly improves the classification with the same computational efficiency.


Smoking history and prior surgical resection predict sensitivity to gefitinib in advanced non-small-cell lung cancer.
Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase, and induces radiographic regression and symptomatic improvement in patients with non-small cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response, never smoking history and adenocarcinoma were associated with survival. We attempted to identify additional clinical features associated with response and survival. We reviewed medical records and imaging studies of all 68 NSCLC patients treated by gefitinib monotherapy in our institution. We identified patients experiencing disease control and compared their clinical features with those of other patients. We considered partial response, stable disease or incomplete response and stable disease to be evidence of disease control. Univariate and multivariate analysis were performed to determine predictive and prognostic factors associated with disease control and survival. Of 68 patients, 20 (29.4%) experienced disease control. Variables identified as significant for disease control with gefitinib included never smoking history (p=0.0128) and history of curative surgical resection (p=0.0007) on multivariate analysis. Variables identified as significant for overall survival included never smoking history (p=0.0128), history of curative surgical resection (p=0.0007), and performance status (PS) of 0 and 1 (p=0.0001) on multivariate analysis. Our findings suggest that never smoking history and history of curative surgical resection are key factors for disease control and prognostic factors in patients with NSCLC treated with gefitinib.


Effectiveness of Benzodiazepine Receptor Agonists in the Treatment of Insomnia: An Examination of Response and Remission Rates.
To examine the real-world effectiveness of benzodiazepine receptor agonists (BzRAs) by quantifying response and remission rates in a clinical sample receiving chronic BzRA treatment for insomnia. Participants were outpatients (N = 193; 72% female; 55.2 ± 11.1 year) who had an insomnia diagnosis per medical records, and who were taking a therapeutic dose of BzRA for their insomnia. Endpoints were nocturnal sleep disturbance and Insomnia Severity Index (ISI) scores. A reduction meeting the criterion for the minimally important difference in ISI scores (change ≥ 6) constituted "response"; "remission" was inferred when symptoms fell below the clinical cutoff (ISI < 11). Most participants (71%) used BzRAs at least 5 nights per week. Mean ISI scores were significantly lower (t = 22.31; p < .01) while on BzRAs than when untreated, but remained in the clinical range (mean = 11.0; standard deviation = 5.7). Although 76.7% responded to treatment, only 47.7% remitted. The majority (68.9%) of participants had a sleep-onset latency > 30 minutes and/or wake-time after sleep onset > 60 minutes while on BzRAs. After controlling for gender and insomnia severity when untreated, odds of insomnia persistence despite BzRA use were 2 times higher in patients with comorbid medical [odds ratio (OR) = 2.39; 95% confidence interval (CI) = 1.20% to 4.77%; p < .05] and psychiatric disorders (OR = 2.24; 95% CI = 1.21% to 4.13%; p < .05). This is the first study to distinguish between response and remission in insomnia patients taking BzRAs. Findings suggest that while many insomnia patients respond to chronic BzRA treatment, most do not remit. Remission rates are particularly low for comorbid insomnia, the most prevalent phenotype of the disorder.


Extrinsic grouping factors in motion-induced blindness.
We investigated how various grouping factors altered subjective disappearances of the individual targets in the motion-induced blindness display. The latter relies on a moving mask to render highly salient static targets temporarily subjectively invisible. Specifically, we employed two extrinsic grouping factors, the connectedness and the common region, and examined whether their presence would make targets more resilient against the suppression. In addition, we investigated whether the presence of an illusory Kanizsa triangle would affect the suppression of the inducing Pac-Man elements. We quantified the perceptual dynamics using the proportion of the disappearance time (this indicates whether targets became more resilient against the suppression), and the proportion of simultaneous disappearance and reappearance events (characterizes the tendency for the targets to disappear or reappear as a group). We report that a single mask that encompassed all targets (a common region grouping) significantly increased the proportion of simultaneous disappearance and reappearance events, but had no effect on the proportion of the disappearance time. In contrast, a line that connected two targets significantly decreased the total invisibility time, but had no impact on the simultaneity of the disappearance and reappearance events. We found no statistically significant effect of the presence of the illusory Kanizsa triangle on either measure. Finally, we found no interaction either between the common region and the connectedness or between the common region and the presence of the illusory Kanizsa triangle. Our results indicate that extrinsic grouping factors might influence the perception differently than the intrinsic ones and highlight the importance of using several measures to characterize the perceptual dynamics, as various grouping factors might affect it differentially.


[Novelties and new possibilities in the radiological diagnostics of kidney and ureter tumors].
The author analyses the opportunities granted by diagnostic imaging for the early perception of kidney and urethral tumors and exact tumor staging. The wide-scale application of non-invasive ultrasound scans has lead to an increase in incidentalomas. Volumetric (multidetector or dual source) CT scans, the various MR techniques and, more recently, PET/CT scans have largely contributed to the exact preoperative staging of tumorous diseases, and help characterize the tumors found. In the case of small kidney tumors, attempts are made to decide which masses require operation and which do not, based on the tumor's absorption of the contrast agent and its wash-out intensity as observed by dynamic contrast-enhanced scans. The author points out that despite the achieved development, especially in terms of small tumors, image-guided biopsies still play a significant role. Medical imaging techniques are also indispensable for post-therapy follow-up of patients (PET/CT, CT and MR perfusion imaging).


Physiological versatility of the genus Rhodocista.
A new purple bacterium (strain T4), capable of heterotrophic aerobic and phototrophic anaerobic growth, was isolated from waste water of a noodle factory near Hanoi, Vietnam. A comparison of 16S rDNA sequences revealed its association with the genus Rhodocista. The isolate, tentatively named "Rhodocista hanoiensis", forms cysts after growth on butyrate-containing plates at 42 degrees C. The vegetative cells form short (under aerobic conditions) or long curve-shaped rods. In contrast to other species of this genus T4 does not need any supplines (growth factors, not synthesized by the organisms). Comparative studies of T4 with Rhodocista centenaria (Rhodospirillum centenum) and Rhodocista pekingensis revealed a remarkable physiological versatility regarding nutrient spectra and survival properties of this genus.


Positive and negative regulation of megakaryocytopoiesis.
The recently cloned physiological regulator of megakaryocytopoiesis, known as Mpl ligand, thrombopoietin (TPO), megakaryocyte growth and development factor (MGDF) or megapoietin, is undergoing preclinical and clinical trials. This factor is an extremely potent thrombocytopoietic agent in vivo in normal animals, and accelerates platelet recovery in some but not all models of myelosuppression. Together with its apparent lack of adverse effects, the preclinical data suggest that TPO might permit the use of higher doses of chemotherapy in dose-intensive regimens and be useful in patients with ineffective platelet production or production abnormalities. The direct effects of TPO on primitive and various myeloid committed haematopoietic progenitor cells predict that TPO may be used in combination with other cytokines in a variety of clinical disorders. Along with the progress made in the understanding of the positive regulation of megakaryocytopoiesis, accumulating data demonstrate that platelet production is also controlled by negative regulators with potential clinical applications. Some of these regulators are effective in the treatment of essential thrombocythaemia and myeloproliferative disorders, while others seem capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs.


Biomechanical properties of the human umbilical cord.
The umbilical cord is a complex and fascinating structure that connects the fetus to the placenta and encases the umbilical vessels. The response of its tissues to mechanical loading due to fetal movements and uterine contractions is not well understood. The aim of this study is the evaluation of the mechanical properties of the main components of the human umbilical cord. Fresh umbilical cord specimens were collected from neonates born at term of the gestation and submitted to compliance tests. Furthermore, uniaxial tensile and stress-relaxation tests were performed on samples of umbilical vein and Wharton's jelly. Both materials exhibited nonlinear stress-strain response with increasing strain, increasing the elastic modulus (E(high) about 10-20 times E(low)) and significant viscoelastic behavior. In addition, anisotropy of the vein was observed. Although the circumferential properties of the vein (mean E(high) about 2.4 MPa) were similar to those after birth, the longitudinal stiffness of both materials was higher (mean E(high) over 10 MPa) and comparable to that of the ligaments. These findings suggest a mechanism of protection acting against excessive elongations of the cord, which could cause undue restriction of the umbilical vessel area and interference with the fetal blood circulation.


Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.
Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost-effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious-predicted variants in DNA repair genes in familial breast cancer (BC) in a well-characterized and homogeneous population. We analyzed 113 DNA repair genes selected from either an exome sequencing or a candidate gene approach in the GENESIS study, which includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data were filtered for rare loss-of-function variants (LoF) and likely deleterious missense variants (MV). We confirmed associations between LoF and MV in PALB2, ATM and CHEK2 and BC occurrence. We also identified for the first time associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike other associated genes, carriers of an ATM LoF had a significantly higher risk of developing BC than carriers of an ATM MV (ORLoF = 17.4 vs. ORMV = 1.6; p Het = 0.002). Hence, our approach allowed us to specify BC relative risks associated with deleterious-predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility. We also highlight that different types of variants within the same gene can lead to different risk estimates.


Degradation of textile dyes by cyanobacteria.
Dyes are recalcitrant compounds that resist conventional biological treatments. The degradation of three textile dyes (Indigo, RBBR and Sulphur Black), and the dye-containing liquid effluent and solid waste from the Municipal Treatment Station, Americana, São Paulo, Brazil, by the cyanobacteria Anabaena flos-aquae UTCC64, Phormidium autumnale UTEX1580 and Synechococcus sp. PCC7942 was evaluated. The dye degradation efficiency of the cyanobacteria was compared with anaerobic and anaerobic-aerobic systems in terms of discolouration and toxicity evaluations. The discoloration was evaluated by absorption spectroscopy. Toxicity was measured using the organisms Hydra attenuata, the alga Selenastrum capricornutum and lettuce seeds. The three cyanobacteria showed the potential to remediate textile effluent by removing the colour and reducing the toxicity. However, the growth of cyanobacteria on sludge was slow and discoloration was not efficient. The cyanobacteria P. autumnale UTEX1580 was the only strain that completely degraded the indigo dye. An evaluation of the mutagenicity potential was performed by use of the micronucleus assay using Allium sp. No mutagenicity was observed after the treatment. Two metabolites were produced during the degradation, anthranilic acid and isatin, but toxicity did not increase after the treatment. The cyanobacteria showed the ability to degrade the dyes present in a textile effluent; therefore, they can be used in a tertiary treatment of effluents with recalcitrant compounds.


Use of locked nucleic acid oligonucleotides to add functionality to plasmid DNA.
The available reagents for the attachment of functional moieties to plasmid DNA are limiting. Most reagents bind plasmid DNA in a non-sequence- specific manner, with undefined stoichiometry, and affect DNA charge and delivery properties or involve chemical modifications that abolish gene expression. The design and ability of oligonucleotides (ODNs) containing locked nucleic acids (LNAs) to bind supercoiled, double-stranded plasmid DNA in a sequence-specific manner are described for the first time. The main mechanism for LNA ODNs binding plasmid DNA is demonstrated to be by strand displacement. LNA ODNs are more stably bound to plasmid DNA than similar peptide nucleic acid (PNA) 'clamps' for procedures such as particle-mediated DNA delivery (gene gun). It is shown that LNA ODNs remain associated with plasmid DNA after cationic lipid-mediated transfection into mammalian cells. LNA ODNs can bind to DNA in a sequence-specific manner so that binding does not interfere with plasmid conformation or gene expression. Attachment of CpG-based immune adjuvants to plasmid by 'hybrid' phosphorothioate-LNA ODNs induces tumour necrosis factor-alpha production in the macrophage cell line RAW264.7. This observation exemplifies an important new, controllable methodology for adding functionality to plasmids for gene delivery and DNA vaccination.


Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.
Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated. Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later. In 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r = 0.360, p<0.001). Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile. Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.


A Novel Imaging System Distinguishes Neoplastic from Normal Tissue During Resection of Soft Tissue Sarcomas and Mast Cell Tumors in Dogs.
To assess the ability of a novel imaging system designed for intraoperative detection of residual cancer in tumor beds to distinguish neoplastic from normal tissue in dogs undergoing resection of soft tissue sarcoma (STS) and mast cell tumor (MCT). Non-randomized prospective clinical trial. 12 dogs with STS and 7 dogs with MCT. A fluorescent imaging agent that is activated by proteases in vivo was administered to the dogs 4-6 or 24-26 hours before tumor resection. During surgery, a handheld imaging device was used to measure fluorescence intensity within the cancerous portion of the resected specimen and determine an intensity threshold for subsequent identification of cancer. Selected areas within the resected specimen and tumor bed were then imaged, and biopsies (n=101) were obtained from areas that did or did not have a fluorescence intensity exceeding the threshold. Results of intraoperative fluorescence and histology were compared. The imaging system correctly distinguished cancer from normal tissue in 93/101 biopsies (92%). Using histology as the reference, the sensitivity and specificity of the imaging system for identification of cancer in biopsies were 92% and 92%, respectively. There were 10/19 (53%) dogs which exhibited transient facial erythema soon after injection of the imaging agent which responded to but was not consistently prevented by intravenous diphenhydramine. A fluorescence-based imaging system designed for intraoperative use can distinguish canine soft tissue sarcoma (STS) and mast cell tumor (MCT) tissue from normal tissue with a high degree of accuracy. The system has potential to assist surgeons in assessing the adequacy of tumor resections during surgery, potentially reducing the risk of local tumor recurrence. Although responsive to antihistamines, the risk of hypersensitivity needs to be considered in light of the potential benefits of this imaging system in dogs.


Separation of bile acids of rat bile by thin-layer chromatography.
The common bile acids of rat bile (chenodeoxycholic, hyodeoxycholic, cholic, alpha-muricholic, and beta-muricholic acids) are completely separated by a new thin-layer chromatographic system.


Masculinity impediments: Internalized masculinity contributes to healthcare avoidance in men and women.
Gender beliefs contribute to men's healthcare avoidance, but little research examines these outcomes in women. This article models healthcare avoidance related to masculine contingencies of self-worth in men and women. Nested path modelling tested relationships between social role beliefs, masculine contingencies of self-worth, barriers to help seeking and avoidance of health care in university and non-university-student adult samples. Results indicated social role beliefs predicted masculine contingencies of self-worth in men but not in women. Regardless of gender, masculine contingencies of self-worth predicted barriers to help seeking, which predicted healthcare avoidance in both men and women. Thus, masculine contingencies of self-worth have downstream consequences for men and women through barriers to help seeking.


Frameless stereotaxic integration of CT imaging data: accuracy and initial applications.
To evaluate the spatial accuracy of a rapid interactive method of transferring computed tomographic (CT) information between its display on a computer screen to its source (test object, operating field), a multidimensional computer combined with a six-jointed position-sensing mechanical arm was tested with a Plexiglas model consisting of 50 rods of varied height and known location, a plastic replica of the skull, and, subsequently, three patients. The median error value between image and real location was 1-2 mm (P > .95), regardless of the registration target sites. The accuracy, however, increased with the selection of widespread registration points, and 95% of all errors were below 3.70 mm (P > .95). The results compare favorably with the four most commonly used stereotaxic framed units. A misregistration error of 0.3-2.2 mm was found during intraoperative correlation between anatomy on the CT display and actual anatomic location in the operative field.


Prominent expansion of circulating lymphocytes bearing gamma T-cell receptors, with preferential expression of variable gamma genes after allogeneic bone marrow transplantation.
The presence of two distinct T-cell receptors (TCR) alpha/beta dimers or gamma/delta dimers, was systematically analyzed in peripheral blood lymphocytes form 26 recipients of allogeneic bone marrow transplants for leukemia. When using monoclonal antibody WT31, which recognizes a common epitope on the alpha/beta heterodimer, the expansion of peripheral CD3+, WT31- cells to 40% of the PBLSs was detected in two patients. In patient 2, the presence of circulating TCR gamma-bearing cells was directly demonstrated with monoclonal antibody Ti gamma A directed against the V gamma 9 J gamma p gene products. From CD3, WT31- clones derived from patients 1 and 2, sequential immunoprecipitations were performed with anti-CD3 and anti-C gamma to determine the CD3-associated structure. Molecular weights of gamma subunits were different in both patients, thus indicating structural heterogeneity. The ability of TCR gamma clones to proliferate when stimulated with anti-CD3 beads was observed for clones from patient 2, whereas this response required exogenous interleukin-2 for clones from patient 1. We have already shown that the TCR gamma cells from patient 1 might have played a role in the immunodeficient state. Similar conclusions cannot be drawn from patient 2. Southern blot analysis of total PBL gamma cell lines and clones indicated that this major circulating subset of TCR gamma cells retained a TCR beta gene in germline configuration and preferentially expressed a single V gamma gene, V gamma 5 for patient 1 and V gamma 9 for patient 2.


Preliminary comparison of landscape pattern-normalized difference vegetation index (NDVI) relationships to Central Plains stream conditions.
We explored relationships of water quality parameters with landscape pattern metrics (LPMs), land use-land cover (LULC) proportions, and the advanced very high resolution radiometer (AVHRR) normalized difference vegetation index (NDVI) or NDVI-derived metrics. Stream sites (271) in Nebraska, Kansas, and Missouri were sampled for water quality parameters, the index of biotic integrity, and a habitat index in either 1994 or 1995. Although a combination of LPMs (interspersion and juxtaposition index, patch density, and percent forest) within Ozark Highlands watersheds explained >60% of the variation in levels of nitrite-nitrate nitrogen and conductivity, in most cases the LPMs were not significantly correlated with the stream data. Several problems using landscape pattern metrics were noted: small watersheds having only one or two patches, collinearity with LULC data, and counterintuitive or inconsistent results that resulted from basic differences in land use-land cover patterns among ecoregions or from other factors determining water quality. The amount of variation explained in water quality parameters using multiple regression models that combined LULC and LPMs was generally lower than that from NDVI or vegetation phenology metrics derived from time-series NDVI data. A comparison of LPMs and NDVI indicated that NDVI had greater promise for monitoring landscapes for stream conditions within the study area.


[Ethics of biomedical research: questions about patient information].
All recommendations and laws concerning biomedical research, including the most recent in France in 2012, emphasize the quality of patient information to justify its participation. To optimize practices, it is important to take into account the central issues: what limits of information? What role for the relatives and family in the decision in case of disability or vulnerability of a patient? What need for specific information for long protocol and follow-up cohort? What information about research results?


Identification of an Amygdala-Thalamic Circuit That Acts as a Central Gain Mechanism in Taste Perceptions.
Peripheral sources of individual variation in taste intensity perception have been well described. The existence of a central source has been proposed but remains unexplored. Here we used functional magnetic resonance imaging in healthy human participants (20 women, 8 men) to evaluate the hypothesis that the amygdala exerts an inhibitory influence that affects the "gain" of the gustatory system during tasting. Consistent with the existence of a central gain mechanism (CGM), we found that central amygdala response was correlated with mean intensity ratings across multiple tastants. In addition, psychophysiological and dynamic causal modeling analyses revealed that the connection strength between inhibitory outputs from amygdala to medial dorsal and ventral posterior medial thalamus predicted individual differences in responsiveness to taste stimulation. These results imply that inhibitory inputs from the amygdala to the thalamus act as a CGM that influences taste intensity perception.SIGNIFICANCE STATEMENT Whether central circuits contribute to individual variation in taste intensity perception is unknown. Here we used functional magnetic resonance imaging in healthy human participants to identify an amygdala-thalamic circuit where network dynamics and connectivity strengths during tasting predict individual variation in taste intensity ratings. This finding implies that individual differences in taste intensity perception do not arise solely from variation in peripheral gustatory factors.


Automatic risk prediction of intracranial aneurysm on CTA image with convolutional neural networks and radiomics analysis.
Intracranial aneurysm (IA) is a nodular protrusion of the arterial wall caused by the localized abnormal enlargement of the lumen of a brain artery, which is the primary cause of subarachnoid hemorrhage. Accurate rupture risk prediction can effectively aid treatment planning, but conventional rupture risk estimation based on clinical information is subjective and time-consuming. We propose a novel classification method based on the CTA images for differentiating aneurysms that are prone to rupture. The main contribution of this study is that the learning-based method proposed in this study leverages deep learning and radiomics features and integrates clinical information for a more accurate prediction of the risk of rupture. Specifically, we first extracted the provided aneurysm regions from the CTA images as 3D patches with the lesions located at their centers. Then, we employed an encoder using a 3D convolutional neural network (CNN) to extract complex latent features automatically. These features were then combined with radiomics features and clinical information. We further applied the LASSO regression method to find optimal features that are highly relevant to the rupture risk information, which is fed into a support vector machine (SVM) for final rupture risk prediction. The experimental results demonstrate that our classification method can achieve accuracy and AUC scores of 89.78% and 89.09%, respectively, outperforming all the alternative methods. Our study indicates that the incorporation of CNN and radiomics analysis can improve the prediction performance, and the selected optimal feature set can provide essential biomarkers for the determination of rupture risk, which is also of great clinical importance for individualized treatment planning and patient care of IA.


Identification and comparison of factors related to academic failure in medical colleges; A Bi-centre, comparative study.
To evaluate student's perceptions related to their academic failure, and to compare these perceptions with their nationality. The non-interventional, bi-national, comparative study was conducted in medical colleges of Pakistan and Saudi Arabia from 2015 to 2017 and comprised medical students who had scored less than 50% in their professional examinations. Data was collected using a pre-designed 22-item questionnaire that was scored by the students on a 5-point scale. Data was analysed using SPSS 23. Of the 210 students, 115(55%) were Pakistanis and 95(45%) were Saudis. Common reasons of failure identified were information overload 114(50%), difficult examination 101(48%), poor teaching skills of teachers 82(39%), system of education 75(36%) and unfair examination 78(37%). In terms of nationality, 11 items were found significant (p<0.05). Regardless of cultural and environmental differences in factors contributing towards failure in students of different countries, the risk factors were found to be common, with most students blaming external factors rather than internal ones.


B-Cell non-Hodgkin's lymphoma in children and adolescents: surface antigen expression and clinical implications for future targeted bioimmune therapy: a children's cancer group report.
Paraffin-embedded diagnostic biopsy materials from a large cohort of pediatric and adolescent patients with mature B-cell non-Hodgkin's lymphoma (NHL) treated on the Children's Cancer Group arm of an international cooperative trial were studied to determine their phenotypic features and the feasibility of using targeted bioimmune therapies. There were 345 patients eligible for analysis: 208 with Burkitt's lymphoma (BL), 43 with high-grade B-cell lymphoma, Burkitt-like (HGBL), and 94 with diffuse large B-cell lymphoma (DLBCL). Samples were immunophenotyped centrally using a standard panel that included CD20, CD79a, CD3, and CD45RO. Additional staining with CD22 was performed on a subset of cases. Immunophenotypic studies showed positive staining with CD20 in 100% of cases of BL and HGBL and in 98% of cases with DLBCL. CD22 expression was present in all cases of BL and DLBCL and in 87% of cases HGBL. This study indicates that immune-based therapies such as rituximab and ibritumomab-tiuxetan (anti-CD20) and epratuzumab (anti-CD22) are feasible in pediatric cases of mature B-cell NHLs.


Generation Y and the Integrated Plastic Surgery Residency Match: A Cross-sectional Study of the 2011 Match Outcomes.
Plastic surgery is the most competitive specialty in medicine. We sought to identify factors associated with the successful match of generation Y applicants into integrated plastic surgery residency. We utilized the most recent data from the Charting Outcomes in the Match published by the National Resident Matching Program in 2011. We had data on US senior or independent applicant status, Alpha Omega Alpha (AOA) status, attendance of top 40 medical schools, advanced degree status, and number of contiguous ranks within plastic surgery. Our main outcome measure was match status. A total of 81 out of 197 applicants (41.1%) successfully matched into integrated plastic surgery in the 2011 main match. US seniors matched at a significantly higher rate compared to independent applicants (44.0% vs 24.1%, P = 0.044). Matched US seniors were more likely to have AOA membership compared to unmatched US seniors (45.9% vs 27.7%, P = 0.014) and attend a top 40 medical school (52.7% vs 35.1%, P = 0.022). There were no differences in terms of advanced degrees between matched and unmatched US seniors. Unmatched US seniors were more likely to have 3 or fewer contiguous ranks of plastic surgery residency programs than matched US seniors (86.2% vs 68.9%, P = 0.007). US senior status, AOA membership, and attendance at a top 40 medical school are predictors of matching into integrated plastic surgery. Program directors need to be aware of the background of the millennial applicants to recruit and maintain top residents.


[Essential mixed cryoglobulinemia with kidney involvement].
Essential mixed cryoglobulin associated with rapidly progressive glomerulonephritis has been observed in a 64-year-old patient. The cryoglobulin consisted of monoclonal IgM-kappa and polyclonal IgG and displayed rheumatoid-factor activity. The antinuclear antibody test was negative. In the immunofluorescent method renal biopsy showed positive staining for IgG; IgM and the early and late complement components. The rheumatoid factor activity of the renal IgM deposits was demonstrated by binding of fluorescent aggregated IgG. There is thus evidence that the vasculitis observed in essential mixed cryoglobulin is caused by IgM-IgG complexes. The differentiation of essential mixed cryoglobulin from lupus nephritis with cryoglobulins is discussed.


Contrast-Enhanced Ultrasound Reveals Exercise-Induced Perfusion Deficits in Claudicants.
Contrast-Enhanced Ultrasonography (CEUS) is an imaging modality allowing perfusion quantification in targeted regions of interest of the lower extremity that has not been possible with color-flow imaging or with measurement of ankle brachial indices. We developed a protocol to quantify lower extremity muscle perfusion impairment in PAD patients in response to exercise. Thirteen patients with Rutherford Class I-III Peripheral Arterial Disease (PAD) and no prior revascularization procedures were recruited from the Baltimore Veterans Affairs Medical Center and compared with eight control patients without PAD. CEUS interrogation of the index limb gastrocnemius muscle was performed using an intravenous bolus of lipid-stabilized microsphere contrast before and after a standardized treadmill protocol. Peak perfusion (PEAK) and time to peak perfusion (TTP) were measured before and after exercise. Between and within group differences were assessed. Control subjects demonstrated a more rapid TTP (p<0.01) and an increase in peak perfusion (PEAK, p=0.02) after exercise, when compared to their baseline measures. Patients with PAD demonstrated TTP and PEAK measures equivalent to controls at baseline (p=0.39, p=0.71, respectively). However, they exhibited no significant exercise-induced changes in perfusion (TTP p=0.49 and PEAK 0.67, respectively compared to baseline). After exercise, normal subjects had significantly shorter TTP (p=0.04) and greater PEAK (p=0.02) than PAD patients. Consistent with their lack of ischemic symptoms at rest, class I to III claudicant PAD patients showed similar perfusion measures (TTP and PEAK) at rest. PAD patients, however, were unable to increase perfusion in response to exercise, whereas controls increased perfusion significantly. This corresponds with claudication and limited walking capacity observed in PAD. CEUS with bolus injection offers a convenient, objective, quantitative and visual physiologic assessment of perfusion limitation in specific muscle groups of PAD patients. This has the potential for substantial clinical and research utility.


[Clinical and neurophysiological characteristics of motor cortical responsiveness during prolonged cranial osteoplasty].
The data of global and stimulation poly-EMG were used to estimate the outcomes of multimodality treatment of sequelae of brain injury and stroke, which was based on the vasoactive effects of prolonged cranial osteoplasty. Thirteen patients (7 males and 6 females) aged 19 to 64 (mean 42 +/- 4) years who had signs of left- (n = 2) and right-sided (n = 11) spastic hemiparesis. Global and stimulation poly-EMG, which involved recording and analysis of resting and total EMG under the maximum voluntary tension, M-waves H-reflexes, transcranially evoked potentials. The muscles of the shoulder, forearm, hand, femur, leg, and foot were studied. The surgical procedure developed at the Russian Research Center "VTO" for stimulation of cerebral blood flow in combination with conventional conservative treatments (physiotherapy, therapeutical exercises, and adequate drug therapy) was shown to increase the transmission coefficient of an efferent signal in the motor cortex-spinal motor neurons-muscle system, which is clinically accompanied by improved coordination of simple and complex movements realized with the participation of the muscles of both the paretic and contralateral extremity. The ambiguous effects of the vasoactive factors of prolonged osteoplasty on the functions of unequally modal pathologically changed cerebral motor structures were noted. The findings may be considered as evidence for the low traumatic ability of the VTO's techniques for replacing posttraumatic defects of skull vault bones.


New materials and techniques in prosthodontics.
In looking back over the past few years, dentistry has seen many changes. The newer methods and materials in complete denture prosthodontics, and the update on dental materials has been exciting. The development of many good disposable products is in keeping with other technologic advancements. Unlike aerospace and industry, dentistry has not yet entered the computer age. However, that day is not far off. With the newer materials used in the multiphases of prosthodontics, the astute practitioner can become acquainted with time-saving, clinically orientated dental materials, and new products. The clinician's appreciation of a particular product is based on individual reaction to the disposable qualities, the cost factors, the ease of handling, and the end product. The advantages of time-saving methods are crucial to office overhead today. This article has covered various phases of removable complete dentures, dental materials, and products that are appropriate to those procedures. No particular product or procedure has been specifically recommended. Instead, I have introduced products that I have used and enjoyed. Not all products can be studied and reported, so if certain materials are not mentioned, it is because not enough time was available to pursue every new product or procedure offered to the disciplines of dentistry.


Congenitally dysplastic inferior rectus muscle.
The authors report an unusual presentation of an idiopathic congenitally dysplastic inferior rectus muscle that responded well to surgical correction. Isolated unilateral enlargement of extraocular muscles is rare in children, and there is no definite logical explanation for its cause. A 20-month-old child presented with a congenitally enlarged posterior part of the right inferior rectus muscle with prominent hypotropia and enophthalmos since 10 months of age. Systemic disease work-up, ultrasound B-scan, computed tomography of the orbit and brain, and inferior rectus muscle biopsy were performed. Preoperatively, the child had severe hypotropia of the right eye with retraction of the globe. Work-up for systemic diseases was negative. Computed tomography scan showed thickening of the posterior two-thirds of the inferior rectus muscle. Muscle biopsy showed non-specific fibrotic changes. Strabismus surgery was undertaken at 2 years of age. Hypotropia was reduced significantly postoperatively. Compensatory head position was eliminated.


Deficit of Long-Term Potentiation Induction, but Not Maintenance, in the Juvenile Hippocampus after Neonatal Proinflammatory Stress.
CA3-CA1 long-term potentiation (LTP) in the hippocampal slices from juvenile Wistar rats was studied to reveal factors potentially contributing to different sensitivity to neonatal proinflammatory stress (NPS). NPS was induced by intra-peritoneal injections of bacterial lipopolysaccharide (LPS) to neonatal rats (two injections of LPS, or saline in the control group, consecutively on postnatal days 3 and 5 [PND3 and PND5]). In females, a significant effect of NPS on hippocampus development was associated with modifications of long-term synaptic plasticity, the synapses becoming more resistant to LTP induction. LTP deficit in the slices of the NPS group was not associated with a decrease in LTP maintenance, since late LTP generally corresponded to early LTP magnitude, similar in all groups. Moreover, partial correlation revealed significantly higher residual LTP 1 h after high-frequency stimulation in the NPS groups compared to the corresponding value of early LTP in the control groups, suggesting improved consolidation. Both effects were evident in NPS females. A number of males responded to NPS similarly to females, while others were relatively resistant to NPS exposure, a significant increase in variability of LTP magnitude being revealed in NPS males compared to respective females and the control groups. We suggest that postnatal development of long-term plasticity after NPS is similar in animals of both sexes; however, additional specific factor(s) may promote a relative resistance of the male brain.


Storage of vitamin A in extrahepatic stellate cells in normal rats.
In mammals, vitamin A is primarily stored as retinyl esters in hepatic stellate cells under normal dietary intake of the vitamin. Previously, extrahepatic vitamin A-storing stellate cells have only been identified in animals maintained on a vitamin A-rich diet, and it has not been known whether these cells play a role in normal vitamin A metabolism. The purpose of this study was, to quantify the stellate cell lipid droplet area in hepatic and extrahepatic stellate cells in control rats and in rats fed excess vitamin A. The stellate cells were identified by the gold chloride staining technique, specific autofluorescence of retinyl ester, and by electron microscopy. The stellate cell lipid droplet area was then quantitated by the use of morphometric quantitation. We demonstrated that lipid droplet-containing stellate cells were identified in liver, lung, kidney, and intestine, in normal as well as vitamin A-fed rats. The area of lipid droplets in liver, lung, and intestine stellate cells of normal rats was 0.2, 0.3, and 0.04 mm2 per cm2 tissue, respectively. When the rats were administered excess vitamin A, the hepatic, lung, and intestinal stellate cell lipid droplet area increased about 10-fold, 2-fold, and 40-fold, respectively. Thus the present study shows that extrahepatic stellate cells in lung and intestine of normal rats contain lipid droplets, and that these lipid droplets increase in area when high doses of vitamin A are fed to the animals. These data suggest that not only liver stellate cells but also extrahepatic stellate cells play an important role in vitamin A storage in normal as well as vitamin A-fed animals.


Insights into the Mechanism of the Therapeutic Potential of Herbal Monoamine Oxidase Inhibitors in Neurological Diseases.
Monoamine oxidase (MAO) is an enzyme that catalyzes the deamination of monoamines and other proteins. MAO's hyperactivation results in the massive generation of reactive oxygen species, which leads to a variety of neurological diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and depression-like disorders. Although synthetic MAO inhibitors are clinically available, they are associated with side effects such as hepatotoxicity, cheese reaction, hypertensive crisis, and so on, necessitating the investigation of alternative MAO inhibitors from a natural source with a safe profile. Herbal medications have a significant impact on the prevention of many diseases; additionally, they have fewer side effects and serve as a precursor for drug development. This review discusses the potential of herbal MAO inhibitors as well as their associated mechanism of action, with an aim to foster future research on herbal MAO inhibitors as a potential treatment for neurological diseases.


First report of Pythium aristosporum causing corn stalk rot in China.
Corn (Zea mays L.) stalk rot, caused by various pathogens, is one of the most prevalent corn diseases worldwide. In October 2019, a survey was carried out to determine pathogenic fungi causing corn stalk rot in 3 fields (~120 ha) in Harbin city (44.04°N 125.42°E), Heilongjiang Province, China. In each field, 100 plants at 5 sampling points were assessed at the milk stage (R3) of development. Disease incidence was 12%. Symptomatic plants showed rapid death of the upper leaves, drooping ears and stalks were soft, hollow, watersoaked with white hyphae present on teh outside of the stalk. Pieces of tissue (0.25 cm2) from 15 individual diseased stalks (5 plants/field) were surface disinfested in 0.5% NaOCl for 5 min, rinsed three times in sterile distilled water and cultured on potato dextrose agar (PDA) containing streptomycin (50 μg/mL). After three days of incubation, a total of twelve fungal cultures with uniform characteristics were isolated and subcultured by transferring hyphal tips onto V8. Colonies on V8 selective medium were creamy white and floccus, with a growth rate of 20 mm/day at 26°C in darkness. Oospores were mostly plerotic, and oogonia walls were 1.3 to 2.7 μm thick (n = 50); globose oogonia, 23.9 to 30.5 μm in diameter (n = 50), and had 1 to 8 antheridia. Based on these characteristics, the isolates were identified as Pythium sp. (van der Plaats-Niterink 1981). Genomic DNA was extracted from single conidial cultures of representative isolates (MZYJF1, MZYJF3 and MZYJF7), and the internal transcribed spacer (ITS) region and cytochrome coxidase subunit II (CoxII) gene were amplified and sequenced using the primers ITS1/ITS4 (Yin et al. 2012) and COX2f/COX2r (Hudspeth et al. 2000), respectively. Partial nucleotide sequences of 796 bp and 573 bp for the ITS and COX11 amplicons, respectively, were obtained and deposited in GenBank (accession no. MW447501 for ITS, and MW471006 for COXII). MegaBLAST analysis of the ITS and CoxII sequences of MZYJF1 isolate showed 100% similarity with sequences from P. aristosporum strain ATCC 11101. The isolates were identified as P. aristosporum based on the fact that P. aristosporum has aplerotic oospores and less antheridia per oogonium than P. arrhenomanes (van der Plaats-Niterink 1981). A pathogenicity test was performed on corn cv. Xianyu 335 at tasseling stage (VT) in the field. An oospore suspension, obtained from isolate MZYJF1 grown on V8 agar media for 4 weeks (Green and Jensen, 2000) and diluted to 1×104 oospores/mL using blood cell counting method, was injected into the base of the maize stems of 6 healthy plants (1.5 ml/plant ) using a syringe. Control plants were injected with distilled sterile water. All inoculated plants showed symptoms 25 days after inoculation that were similar to those observed in the field. The oomycete of P. aristosporum was reisolated from symptomatic plants on V8 agar media and identified according to morphological and molecular characteristics. No symptoms were observed on the control plants. P. aristosporum has previously been reported on causing damping-off of pea in the Columbia basin of Central Washington (Alcala et al. 2016) and on soybean in North Dakota (Zitnick-Anderson and Nelson 2015). To our knowledge, this is the first report of P. aristosporum causing corn stalk rot in China. Corn stalk rot caused by P. aristosporum poses a threat to significantly reduce the quality of corn. Thus, its distribution needs to be investigated and effective disease management strategies developed.


Dorsal-enhanced sutures improve tension resistance of tendon repair.
Thirty-six fresh pig flexor tendons were repaired using either the modified Kessler method or the Tang method. Nine tendons from each group were tested in an Instron tensile testing machine with the tendons passing 90 degrees around a pulley. The other nine tendons from each group were pulled linearly by the testing machine. The 2 mm gap formation force of the tendons repaired with the modified Kessler and Tang methods and pulled at 90 degrees were 64%+/-5% and 79%+/-9% respectively of those forces recorded during linear testing. The ultimate strengths of tendons repaired by the modified Kessler and Tang methods and pulled at 90 degrees were 76%+/-6% and 81%+/-8% respectively of the forces measured during linear testing. The percentage gap formation and ultimate strength of the Tang method was significantly higher than that of the modified Kessler suture when the tendons were pulled around a pulley. This demonstrates that the Tang suture, with its main components in the dorsal part of the repaired tendon, has greater tension resistance capacity than conventional tendon sutures which are placed in the middle of the tendon. This study suggests that dorsally-enhanced multiple tendon sutures are better placed to sustain the tension generated during active finger flexion.


Uselessness of a questionnaire for osteoporosis and role of bone mass measurements in predicting tooth loss.
We evaluated whether the number of teeth lost is associated with risk factors for osteoporosis and whether bone mass measurements can add further information. A total of 455 healthy women were enrolled. All the subjects filled in a questionnaire on risk factors for osteoporosis. The bone mineral density (BMD) was measured both by dual X-ray absorptiometry (DXA) and quantitative ultrasound measurements (QUS). On the basis of the questionnaire score 65.1% of the subjects were in the low risk category, 11% in the moderate risk category, 19.3% in the fairly high risk category and 4.6% in the high risk category. Close relationships (P<0.001) were observed between bone mass loss and the questionnaire risk categories. The number of teeth lost significantly increased from normal to osteoporosis groups. High correlations were also found between osteosonographic parameters and the number of teeth lost. Among questionnaire items a significant positive correlation was found only between the number of teeth lost and both age class (P<0.001) and years since menopause (P<0.001). A multiple regression showed that only age class (P<0.001) and ultrasound bone profile index (UBPI) (P=0.041) were independently linked to tooth loss. The results obtained showed that age is the main determinant of tooth loss and that QUS adds further information in identifying patients at a higher risk of tooth loss.


Heavy and light chain pairing of bivalent quadroma and knobs-into-holes antibodies analyzed by UHR-ESI-QTOF mass spectrometry.
The quadroma antibody represents the first attempt to produce a bispecific heterodimeric IgG antibody by somatic fusion of 2 hybridoma cells each expressing monoclonal antibodies with distinctive specificities. However, because of random heavy and light chain pairing, the desired functional bispecific antibody represents only a small fraction of the protein produced. Subsequently, the knobs-into-holes (KiH) approach was developed to enforce correct heavy chain heterodimerization. Assuming equimolar expression of 4 unmodified chains comprising 2 heavy and 2 light chains, the statistical distribution of all paired combinations can be calculated. With equimolar expression as the goal, we transfected HEK cells with 1:1:1:1 plasmid ratios and analyzed the protein A affinity-purified antibodies from the quadroma and KiH approaches qualitatively and quantitatively with regard to the estimated relative amounts of the products using electrospray quadrupole time-of-flight mass spectrometry. Our results show that all expected species are formed, and that, within the methodological limits, the species distribution in the mixtures corresponds approximately to the statistical distribution.


Testicular pathological alterations associated with SARS-CoV-2 infection.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19), which caused one of the pandemics with the highest mortalities with millions of deaths and hundreds of millions of cases to date. Due to its potential for airborne transmission, many studies have focused on SARS-CoV-2 primarily as a respiratory disease. However, the spread of SARS-CoV-2 to non-respiratory organs has been experimentally demonstrated and clinically observed. During autopsy studies, histopathological lesions, and disruption of the blood-testes barrier (BTB) have been observed in the male reproductive tract. Here, we review findings from both autopsy cases and animal models that demonstrate testicular disease due to COVID-19 and present an overview of the pathological alterations that occur in the testes resulting from SARS-CoV-2 infection and explore its potential mechanisms.


Neuroendocrinology and aging.
This short review goes back to early discoveries concerning the neuroendocrinology of aging, discussing the Brown-Sequard experiment on rejuvenation at the end of the 19th century and Steinach's subsequent experiments in the early 20th century. It also considers the seminal experiments of Pierre Ascheim, Ming Tsung Peng and Joseph Meites in the 1960s on the aging of the gonadotrophic axis. Major age-associated changes in neuroendocrine regulatory processes involved in the menopausal transition, andropause, somatopause and adrenopause are also reviewed. Finally, some views on future directions of research into the neuroendocrinology of aging are proposed, based on the pleiotropy of neuroendocrine messengers and functions.


Effects of dietary magnesium excess in White Leghorn hens.
The effects of excess dietary magnesium on White Leghorn laying hens were investigated in two experiments and a third experiment looked at the effect of dietary phosphorus on excess magnesium in the diet. In Experiment 1, magnesium levels of 0.15, 0.8, and 1.2% were fed in a diet containing 2.5% calcium to hens 30 wk of age for 5 wk. A control diet with 3.5% calcium and 0.15% magnesium was also fed. In Experiment 2, hens 65 wk of age fed 3.5% calcium were fed dietary magnesium levels of 0.15, 0.36, 0.53, 0.76, and 0.91% for 4 wk. In these two experiments, excess magnesium reduced egg production, decreased feed consumption, decreased body weight, decreased percentage eggshell, reduced plasma calcium, and increased plasma magnesium and tibia magnesium but changes seen in tibia weight, percentage ash, and tibia calcium and phosphorus were variable. More changes from feeding excess magnesium were seen in the young, high producing hens in Experiment 1. In Experiment 3, hens 50 wk of age were fed a marginal calcium level (2.5%) with an excess of magnesium (0.8%) and a control level of available phosphorus (0.45%) and this was compared to a low (0.25%) and a high level (0.9%) of available phosphorus for a 4-wk experimental period. At the end of the experimental period, hens fed low phosphorus had lower egg production and lower feed consumption than the hens fed higher levels of phosphorus. Body weight was lower in the hens fed the two lower levels of phosphorus. Percentage eggshell was lower than the controls when fed low phosphorus and higher when fed high phosphorus. These results suggest that high phosphorus diets are better than low phosphorus diets when excess magnesium is fed to laying hens. Further study is needed to investigate the role of phosphorus when excess magnesium is fed.


Individual and Occupational Differences in Perceived Organisational Culture of a Central Hospital in Vietnam.
Many hospitals in developing countries, including Vietnam, are facing the challenges of increasingly noncommunicable diseases and the financial autonomy policy from the government. To adapt to this new context requires understanding and changing the current organisational culture of the hospitals. However, little has been known about this in resource-constrained healthcare settings. The objectives of this study were to examine the four characteristics of the organisational culture and test selected individual and occupational differences in the organisational culture of a Vietnam central hospital. In a cross-sectional study using the Organisation Culture Assessment Instrument (OCAI) with the Competing Value Framework (CVF), including 4 factors, Clan, Adhocracy, Hierarchy, and Market, health workers currently working at Quang Nam General Hospital were interviewed. The results indicated the current cultural model was more internally focused with two dominant cultures, Clan and Hierarchy, while, for the desired model, the Clan culture was the most expected one. Comparing between the current and desired pattern, the down trend was found for all types of culture, except the Clan culture, and there were significant differences by domains of organisational culture. Furthermore, the current and desired models were differently distributed by key individual characteristics. These differences have raised a number of interesting directions for future research. They also suggest that, to build a hospital organisational culture to suit both current and future contexts as per employees' assessment and expectation, it is important to take individual and institutional variations into account.


Poly methacrylic acid-alginate semi-IPN microparticles for oral delivery of insulin: a preliminary investigation.
Microparticles of Poly methacrylic acid (P1) and novel semi-interpenetrating network composed of Poly methacrylic acid-alginate (P2) were prepared and their application in oral insulin delivery was evaluated. The microparticles were characterized by scanning electron microscopy (SEM) for morphological studies. Insulin loading onto the microparticles was performed by the diffusion filling method and insulin encapsulated microparticles were subjected to in vitro release study in buffer solution of pH 1.2 and 7.4. The release kinetics at pH 7.4 exhibited sustained release of insulin for more than 5 h in case of PMAA microparticles whereas burst release of insulin (90% of total insulin loaded) within 1 h of study was observed in the case of PMAA-alginate microparticles. At pH 1.2, around 30% of insulin loaded was released from both microparticles within 2 h of study.


Ab initio, artificial neural network predictions and experimental synthesis of mischmetal alloying in Sm-Co permanent magnets.
The use of the mischmetal alloy, comprised of La and Ce in 1 : 3 ratio, as a partial substitute for Sm in the CaCu5-type structure is explored, as a means for the search of viable alternatives for permanent magnets that require fewer steps in the rare earth separation processing. The structural and magnetic properties of the introduced stoichiometry, containing 50% less Sm, are compared to the ones of the SmCo5, LaCo5 and CeCo5 binary compounds by means of ab initio simulations. The capability of artificial neural networks to accurately predict the relationship between structure and total magnetization from DFT calculations in the supercell approach that was employed, is also demonstrated. Experimental fabrication and structural and magnetic characterization of the proposed stoichiometry verifies the structural configuration and provides insight for the macroscopic hard magnetic properties of the material. The reduction of magnetic properties was found to be favorable compared to the respective reduction of the raw materials cost, while measurements of the Cure temperature verify that the proposed compound is still suitable for high temperature applications.


Tetanus toxin is transported in a novel neuronal compartment characterized by a specialized pH regulation.
Tetanus toxin binds specifically to motor neurons at the neuromuscular junction. There, it is internalized into vesicular carriers undergoing fast retrograde transport to the spinal cord. Despite the importance of this axonal transport pathway in health and disease, its molecular and biophysical characterization is presently lacking. We sought to fill this gap by determining the pH regulation of this compartment in living motor neurons using a chimera of the tetanus toxin binding fragment (TeNT HC) and a pH-sensitive variant of the green fluorescent protein (ratiometric pHluorin). We have demonstrated that moving retrograde carriers display a narrow range of neutral pH values, which is kept constant during transport. Stationary TeNT HC-positive organelles instead exhibit a wide spectrum of pH values, ranging from acidic to neutral. This distinct pH regulation is due to a differential targeting of the vacuolar (H+) ATPase, which is not present on moving TeNT HC compartments. Accordingly, inhibition of the vacuolar (H+) ATPase under conditions that completely abolish the intracellular accumulation of acidotrophic dyes does not affect axonal retrograde transport of TeNT HC. However, a functional vacuolar (H+) ATPase is required for early steps of TeNT HC trafficking following endocytosis, and it is localized to axonal vesicles containing TeNT HC. Altogether, these findings indicate that the vacuolar (H+ ATPase plays a specific role in early sorting events directing TeNT HC to axonal carriers but not in their subsequent progression along the retrograde transport route, which escapes acidification and targeting to degradative organelles.


Sacral root stimulation for controlled defecation.
Selective rectal or sphincter neurostimulation aiming at controlled defecation was performed in 10 dogs. While the dogs were under anesthesia, the rectal and rectal neck pressures, balloon expulsion as well as external anal sphincter (EAS) response to stimulation of the second sacral ventral nerve root (S2) and its autonomic and somatic branches were determined. Each of these nerves was stimulated separately using bipolar platinum cuff electrodes. S2 stimulation resulted in rectal and rectal neck pressure elevation as well as increase of EMG activity of EAS without balloon expulsion. Autonomic branch stimulation effected rectal pressure increase and balloon expulsion, while somatic branch stimulation caused increase of rectal neck pressure and EAS EMG activity with no balloon expulsion. S2 stimulation with somatic branch transection produced rectal pressure elevation and balloon expulsion. In contrast to rectal pressure, the rectal neck pressure increased with increasing stimulus frequency. In conclusion, rectal evacuation and sphincteric control could be induced by selective sacral root electrostimulation: S2 stimulation with transection of the somatic branch for the former and pudendal branch stimulation for the latter.


A Signaling Pathway to Mediate the Combined Immunomodulation of Acetylcholine and Enkephalin in Oyster Crassostrea gigas.
Molluscs have evolved a primitive but complete neuroendocrine-immune (NEI) system with a vast array of neurotransmitters to conduct both humoral and cellular immunomodulation. Previous studies have illustrated the immune functions of several key neurotransmitters. However, the combined effects of multiple neurotransmitters and the signaling pathway to mediate such immunomodulation have not been well-understood. In the present study, iTRAQ and LC-ESI-MS/MS approaches were employed to investigate the combined immunomodulation functions of two crucial neurotransmitters, acetylcholine (ACh), and [Met5]-enkephalin (ENK), in oyster Crassostrea gigas. A total number of 5,379 proteins were identified from hemocytes of oysters after the treatments with Ach and ENK separately or simultaneously, and 1,475 of them were found to be significantly up-regulated, while 1,115 of them were significantly down-regulated. The protein expression patterns in the groups treated by ACh and ENK separately were quite similar, which were dramatically different from that in the group treated by ACh+ENK. One hundred seventy-two proteins were found to be differentially expressed in all the three neurotransmitter treatment groups. Functional validation suggested that ACh and ENK possibly modulate the immune response in oyster hemocytes by enhancing pathogen recognition, cell apoptosis, and the enzyme activities of superoxide dismutase (SOD). Moreover, GO enrichment and co-expression network analyses implied that the combined immunomodulation of ACh and ENK might be mediated by p53, EGF-R-ErbB, and Fc gamma R (FcγR) signaling pathways. These results collectively indicated that multiple neurotransmitters executed a combined and ordered immune regulation through common signaling cascades in molluscs, which was under delicate control to maintain the homeostasis.


New Horizons in Antifungal Therapy.
Recent investigations have yielded both profound insights into the mechanisms required by pathogenic fungi for virulence within the human host, as well as novel potential targets for antifungal therapeutics. Some of these studies have resulted in the identification of novel compounds that act against these pathways and also demonstrate potent antifungal activity. However, considerable effort is required to move from pre-clinical compound testing to true clinical trials, a necessary step toward ultimately bringing new drugs to market. The rising incidence of invasive fungal infections mandates continued efforts to identify new strategies for antifungal therapy. Moreover, these life-threatening infections often occur in our most vulnerable patient populations. In addition to finding completely novel antifungal compounds, there is also a renewed effort to redirect existing drugs for use as antifungal agents. Several recent screens have identified potent antifungal activity in compounds previously indicated for other uses in humans. Together, the combined efforts of academic investigators and the pharmaceutical industry is resulting in exciting new possibilities for the treatment of invasive fungal infections.


Treatment outcomes in childhood acute lymphoblastic leukemia: 40-year experience from a single tertiary center in Thailand.
Studies on the long-term treatment outcomes of childhood acute lymphoblastic leukemia (ALL) in resource-limited countries are scarce. The purpose of this study was to assess the evolution of survival outcomes of pediatric ALL in a tertiary care center in Thailand over a 40-year period. We retrospectively reviewed the medical records of pediatric patients who were diagnosed with ALL and treated at our center between June 1979 and December 2019. We classified the patients into 4 study periods depending on the therapy protocol used to treat the patients (period 1: 1979-1986, period 2: 1987-2005, period 3: 2006-2013, and period 4: 2014-2019). The Kaplan-Meier method was used to determine overall and event-free survival (EFS) for each group. The log-rank test was used to identify statistical differences. Over the study period, 726 patients with ALL were identified, 428 boys (59%) and 298 girls (41%), with a median age at diagnosis of 4.7 years (range: 0.2-15 years). The study periods 1, 2, 3, and 4 had 5-year EFS rates of 27.6%, 41.6%, 55.9%, and 66.4%, and 5-year overall survival (OS) rates of 32.8%, 47.8%, 61.5%, and 69.3%, respectively. From periods 1 to 4, both the EFS and OS rates increased significantly (p <. 0001). Age, study period, and white blood cell (WBC) count were all significant prognostic indicators for survival outcomes. The OS of patients with ALL treated in our center improved significantly over time from 32.8% in period 1 to 69.3% in period 4.


Periodontal Diseases and Heart Diseases: A Systemic Review.
Up to 50% of people worldwide are affected by periodontal disease (PD); cardiovascular diseases are a serious concern for the major portion of the world's population. Observational data have shown a connection between PD and CVD. The current systemic review investigates the incidence of the CVD in individuals with PD through various designs of the previous research. An extensive online search in the various databanks of EMBASE, Medline, Pubmed, and Scopus was conducted. The keywords searched were: "PD, CVD, myocardial infarction, coronary heart disease (CHD), and stroke; technique of diagnosis and the degree of PD were assessed clinically or by self-report." The studies selected were longitudinal research design and randomized trials. To ascertain the risk of mortality due to cardiac issues in periodontal diseases, meta-analysis, and meta-regression were carried out. The diagnosis techniques for periodontal diseases, severity, and impact of gender, were also examined. After full-text screening, 32 longitudinal cohort studies were included. PD patients had a significantly greater risk of CVD than non-PD patients (RR: 1.20). Clinical and self-reported PD diagnoses did not differ in CVD risk (RR = 0.97). Men were at increased risk for both severe PD (RR: 1.25), and CVD (RR: 1.16). The risk of stroke was the highest among all forms of CVD (RR = 1.24), and the risk of CHD was significantly elevated (RR = 1.14). Current review showed that populations with PD consistently and modestly have an elevated risk of CVD. Men and those with severe PD are at higher CVD risk, which suggests population-targeted therapies may be helpful.


Low-vision rehabilitation in Italy: Cross-sectional data from the Device and Aids Registry (D.A.Re).
We are reporting on the characteristics of low-vision adults attending large rehabilitation services which provide data to D.A.Re (Devices & Aids REgister) in Italy. D.A.Re aims to gather information about low-vision aids owned by Italian patients with visual impairment. We included consecutive patients attending low-vision rehabilitation centres providing data to D.A.Re from 2019 to July 2021. Demographic features, self-reported use of technology and aids, vision performance, and the Instrumental Activity of Daily Living (IADL) score were collected. 720 patients were included in the D.A.Re. About half of the patients were affected by Age-related Macular Degeneration (389, 54.9%). Patients reported a long interval between onset of vision disability and access to low-vision rehabilitation, which was over two years in almost 30% of cases. Blindness registration status was almost complete when reported, but almost 40% were unable to report on this. IADL scores were higher for younger people and those with better visual acuity and critical print size (CPS), and lower for visual field restriction (p < 0.01 for all predictors). Of interest, better IADL scores were recorded for those with computer knowledge who used optical aids and software in univariate analyses and multivariate analyses, adjusting for level of visual disability and employment status (p < 0.01 for all predictors). We report on the profile of low-vision patients using rehabilitation services in Italy. Longitudinal data during and after vision rehabilitation were collected. Our results support the validity of the D.A.Re to monitor the use of low-vision devices in Italy.


Moths sense but do not learn flower odors with their proboscis during flower investigation.
Insect pollinators, such as the tobacco hawkmoth Manduca sexta, are known for locating flowers and learning floral odors by using their antennae. A recent study revealed, however, that the tobacco hawkmoth additionally possesses olfactory sensilla at the tip of its proboscis. Here, we asked whether this second 'nose' of the hawkmoth is involved in odor learning, similar to the antennae. We first show that M. sexta foraging efficiency at Nicotiana attenuata flowers increases with experience. This raises the question whether olfactory learning with the proboscis plays a role during flower handling. By rewarding the moths at an artificial flower, we show that, although moths learn an odor easily when they perceive it with their antennae, experiencing the odor just with the proboscis is not sufficient for odor learning. Furthermore, experiencing the odor with the antennae during training does not affect the behavior of the moths when they later detect the learned odor with the proboscis only. Therefore, there seems to be no cross-talk between the antennae and proboscis, and information learnt by the antennae cannot be retrieved by the proboscis.


Environmental occurrence, analysis and human exposure to the flame retardant tetrabromobisphenol-A (TBBP-A)-A review.
TBBP-A is a high production volume chemical applied widely as a flame retardant in printed circuit boards. Recent studies have raised concern over potential harmful implications of TBBP-A exposure in human and wildlife, leading to its classification under group 2A "Probably carcinogenic to humans" by the International Agency for Research on Cancer. This article provides a comprehensive review of the available literature on TBBP-A analysis, environmental levels and human exposure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been identified as the method of choice for robust, accurate and sensitive analysis of TBBP-A in different matrices. TBBP-A has been detected in almost all environmental compartments all over the world, rendering it a ubiquitous contaminant. Human exposure studies revealed dust ingestion and diet as the major pathways of TBBP-A exposure in the general population. Toddlers are likely to be more exposed than adults via accidental indoor dust ingestion. Moreover, exposure to TBBP-A may occur prenatally and via breast milk. There are no current restrictions on the production of TBBP-A in the EU or worldwide. However, more research is required to characterise human exposure to TBBP-A in and around production facilities, as well as in e-waste recycling regions.


Semi-Supervised Graph Regularized Deep NMF With Bi-Orthogonal Constraints for Data Representation.
Semi-supervised non-negative matrix factorization (NMF) exploits the strengths of NMF in effectively learning local information contained in data and is also able to achieve effective learning when only a small fraction of data is labeled. NMF is particularly useful for dimensionality reduction of high-dimensional data. However, the mapping between the low-dimensional representation, learned by semi-supervised NMF, and the original high-dimensional data contains complex hierarchical and structural information, which is hard to extract by using only single-layer clustering methods. Therefore, in this article, we propose a new deep learning method, called semi-supervised graph regularized deep NMF with bi-orthogonal constraints (SGDNMF). SGDNMF learns a representation from the hidden layers of a deep network for clustering, which contains varied and unknown attributes. Bi-orthogonal constraints on two factor matrices are introduced into our SGDNMF model, which can make the solution unique and improve clustering performance. This improves the effect of dimensionality reduction because it only requires a small fraction of data to be labeled. In addition, SGDNMF incorporates dual-hypergraph Laplacian regularization, which can reinforce high-order relationships in both data and feature spaces and fully retain the intrinsic geometric structure of the original data. This article presents the details of the SGDNMF algorithm, including the objective function and the iterative updating rules. Empirical experiments on four different data sets demonstrate state-of-the-art performance of SGDNMF in comparison with six other prominent algorithms.


Evaluation of revascularization after total arch replacement in common carotid artery occlusion.
Occlusion of the common carotid artery (CCA) is rare. CCA occlusion (CCAO) can present as drowsiness and right hemiplegia related to emboli after total arch replacement. Although we selected a follow-up at first because color duplex sonography showed retrograde flow from the left external carotid artery to the internal carotid artery, this patient had epilepsy and single-photon emission computed tomography (SPECT) acquired quantitative results of actual brain perfusion and showed insufficient collateral blood flow. To improve brain perfusion, we performed a bypass of the left subclavian artery to left CCA bypass. Postoperatively, the patient did not have epilepsy and drowsiness. Also, right hemiplegia improved enough for him to walk with support. SPECT showed increased left cerebral flow (the asymmetry ratio was 71% to 81%). Evaluation of the carotid artery with color duplex sonography alone was insufficient when CCAO showed retrograde or collateral flow. We should have performed quantitative evaluation with SPECT at the same time.


Thermal decomposition of peroxy acetyl nitrate CH3C(O)OONO2.
The thermal decomposition of peroxy acetyl nitrate (PAN) is investigated by low pressure flash thermolysis of PAN highly diluted in noble gases and subsequent isolation of the products in noble gas matrices at low temperatures and by density functional computations. The IR spectroscopically observed formation of CH3C(O)OO and H2CCO (ketene) besides NO2, CO2, and HOO implies a unimolecular decay pathway for the thermal decomposition of PAN. The major decomposition reaction of PAN is bond fission of the O-N single bond yielding the peroxy radical. The O-O bond fission pathway is a minor route. In the latter case the primary reaction products undergo secondary reactions whose products are spectroscopically identified. No evidence for rearrangement processes as the formation of methyl nitrate is observed. A detailed mapping of the reaction pathways for primary and secondary reactions using quantum chemical calculations is in good agreement with the experiment and predicts homolytic O-N and O-O bond fissions within the PAN molecule as the lowest energetic primary processes. In addition, the first IR spectroscopic characterization of two rotameric forms for the radical CH3C(O)OO is given.


Genetic diversity and antimicrobial resistance profile of Enterococcus faecalis isolated from broilers with vertebral osteomyelitis in Southeast Brazil.
Vertebral osteomyelitis (VO) is a worldwide emerging disease that affects broilers. Recently, the isolation of Enterococcus faecalis in cases of the disease has been described. This study aimed at determining the genetic diversity and antimicrobial resistance profile of 12 E. faecalis strains isolated from broilers with VO. Strains were isolated from nine flocks from six farms in a high-density poultry production area in Southeast Brazil and were evaluated using multilocus sequence typing and phylogenetic analysis. Antimicrobial susceptibility tests and PCR were performed to detect antimicrobial resistance genes. E. faecalis isolates belonged to different sequence types (ST), six of which (ST49, ST100, ST116, ST202, ST249, and ST300) have been previously described. Strains ST708 and ST709 were newly identified in this study. Strain ST49 was most frequently isolated (50% of the flocks) from the analysed VO cases. No phylogenetic or phylogeographic relationship was found among the strains. The VO isolated E. faecalis strains showed highest resistance to aminoglycosides, mainly gentamicin (40%), but were highly susceptible to vancomycin (10%). Aminoglycoside resistance genes were detected in seven E. faecalis strains, and AAC6'-APH2″ genes were most frequently detected. The results showed that E. faecalis strains isolated from recently reported VO cases were highly diverse genetically. The diversity of genotypes in circulation in the analysed flocks, without apparent relationship among them, raises questions on aetiopathogenesis of the disease in broilers and evolutionary aspects of E. faecalis.


Ventricular premature beats: screening and induction tests in normal men.
Effective future research on the significance of ventricular premature beats (VPB) and their therapeutic suppression require improved and simpler methods for arrhythmia detection, characterization, and measurement. This study considers the comparative yield, repeatability, and validity of several methods of VPB detection and induction in a sample of the general population of middle-aged men. Isometric exercise inducers VPB. Treadmill exercise both induces and suppresses VPB. Cartotid sinus pressure and cold stress provide a small extra yield of VPB.


Rate of effect of surgical margins after breast conserving surgery and estimation of direct costs.
Assessment of the reoperation rate in patients with positive resection margins after initial breast-conserving surgery for breast cancer and estimation of the cost to the hospital. 146 patients with diagnosis of invasive breast cancer were included, who were initially intervened with conservative surgery by the Gynecology and Obstetrics Service of Hospital Universitario de Tarragona Juan XXIII (HUTJ23) during the years 2018 and 2019. We calculated the rate of involvement of the surgical margins of the resection piece after initial conservative surgery, establishing in which cases it was necessary to carry out a second resection, estimating the added direct costs of the second surgical procedure, and comparing them with the costs established by the Catalan Health Service according to the level of the hospital and the Diagnosis-Related Groups (DRG) established by the National Health System. The rate of positive margins after initial conservative surgery was 20.55% and 19.17% patients underwent reoperation, generating a total expense of € 129.696,89, € 82.654,34 in conservative surgeries (€ 3.757,01 on average per patient) and € 47.042,55 in mastectomies (€ 6.720,36 on average per patient). Margin involvement after breast-conserving surgery is synonymous for reoperation, this involves a series of direct costs. It is advisable to control the factors related to affected margins to minimize their impact.


[Diagnostic problems of choledochal cysts in the adult].
Choledochal cysts are rare malformations of the biliary tree, the precise pathogenesis of which remains unclear. The authors present the case of a 21-year-old man with a choledochal cyst and discuss the main issues regarding the diagnosis and treatment of this uncommon lesion. In particular, of all the diagnostic techniques available, magnetic resonance cholangiopancreatography (MRCP) could become the imaging technique of choice for defining the pancreatobiliary ductal anatomy with at least the same degree of accuracy as that of diagnostic ERCP, while avoiding the potential complications associated with the latter. The patient was treated by surgical operation and, after a 12 month follow-up, is disease-free. Surgical treatment is necessary owing to the possibility of malignant transformation.


Ultrasonically guided percutaneous drainage of breast abscess.
Percutaneous drainage of abscess under ultrasound guidance is a well established modality. Its use in breast abscess has still not found wide application. The present study on 25 consecutive cases of breast abscess with success rate of 84% is an attempt to recommend routine use of this modality wherever the facilities exist.


A comparative study of interaction of ibuprofen with biocompatible polymers.
In this paper we are reporting the interaction of a non-steroidal anti-inflammatory drug ibuprofen (IBF) with various biocompatible polymers. Being amphiphilic, the drug interacts with the polymers similar to the interaction of surfactants and polymers. Therefore, we have considered the polymer-amphiphile interaction approach using conductimetry. The polymers of different charges (cationic, anionic, and nonionic) have been taken for the study. It was found that the critical aggregation concentration (cac) decreases on increasing the polymer concentrations of cationic as well as nonionic polymers whereas it increases for anionic polymers. The results imply that anionic IBF interacts with cationic and nonionic polymers more strongly as compared to the anionic polymers. A possible anionic-anionic repulsion is responsible for the weak interaction of IBF with anionic polymers. On the other side, the critical micelle concentration (cmc) increases for all polymers which is a usual indication of the interaction between amphiphiles and polymers. Free energies of aggregation (ΔG(agg)) and micellization (ΔG(mic)) were also computed with the help of degrees of micelle ionization obtained from the specific conductivity - [IBF] isotherms.


Identifying Collisions of Various Molecularities in Molecular Dynamics Simulations.
We present a method based on kinetic molecular theory that identifies reactions of various molecularities in molecular dynamics (MD) simulations of bulk gases. The method allows characterization of the thermodynamic conditions at which higher than bimolecular reactions are a factor in the mechanisms of complex gas-phase chemistry. Starting with Bodenstein's definition of termolecular collisions we derive analytical expressions for the frequency of higher molecularity collisions. We have developed a relationship for the ratio of the frequencies of termolecular to bimolecular collisions in terms of the temperature, density, and collision times. To demonstrate the method, we used ReaxFF in LAMMPS to carry out MD simulations for NVT ensembles of mixtures of H2-O2 over the density range 120.2-332.7 kg m-3 and temperature range 3000-5000 K. The simulations yield ReaxFF-based predictions of the relative importance of termolecular collisions O2···H2···O2 and bimolecular collisions O2···H2 in the early chemistry of hydrogen combustion.