Dilution of PAHs loadings of particulate matter in air, dust and rivers in urban areas: A comparative study (Tehran megacity, Iran and city of Tübingen, SW-Germany).
PAHs (polycyclic aromatic hydrocarbons) in urban areas are usually bound to particles. Concentrations are different in different compartments (airborne particles, street dust, suspended sediments in rivers and channels). This study follows concentrations of PAHs from particles in air to street dust and finally suspended sediments in the city of Tehran, Iran compared to Tübingen, Germany. Data sets are based on own investigations (PAHs on suspended sediments), or taken from literature studies (PAHs in street dust and airborne particles). Based on a cross-comparison of concentrations of PAHs on particles, and their congener distribution patterns, the occurrence, interrelation (exchange and mixing processes), as well as possible dilution processes among PAHs in the different particle classes are disentangled. Results show that for Tehran and Tübingen PAHs in airborne particles are very high (in the range of 500 mg kg-1). However, in street dust and suspended sediments PAHs concentrations on particles are around 100 times lower. Surprisingly concentrations in street dust and suspended sediments are 5 to 10 times lower in Tehran (average 0.5 mg kg-1) than in Tübingen (average 5 mg kg-1). Since it is unlikely that PAHs emissions are lower in the Tehran megacity, an effective dilution of the atmospheric signal by uncontaminated (background) particles is hypothesized. Uncontaminated particles may stem from wind erosion of bare surfaces, construction and sand mining sites or even dust from the desert areas, which are frequent in arid climate in Tehran.


Identifying periods of heightened susceptibility to lead exposure in relation to behavioral problems.
Lead exposure is associated with behavioral problems in children, but the age(s) of greatest susceptibility to low-level lead exposure is unknown. We evaluated the association of repeated blood lead concentrations with parent-reported behaviors to identify periods of heightened susceptibility during infancy and childhood (HOME Study; Cincinnati, OH; 2003-2006; n = 244). We quantified lead in whole blood samples (ages 1, 2, 3, 4, 5, and 8 years) and assessed behavior using the Behavioral Assessment System for Children-2 (BASC-2; ages 2, 3, 4, 5, and 8 years). We used multiple informant models and modified Poisson regression to estimate covariate-adjusted associations of ln-transformed blood lead concentrations with continuous BASC-2 T-scores and the relative risk of behavior scores classified as at-risk or clinically significant, respectively. We observed trends indicating that higher blood lead concentrations at all ages were adversely associated with scores on behavioral scales. On the Externalizing Problems and Adaptive Skills scales, these associations were strongest for blood lead concentrations at age 8 years (β = 3.1-point; 95% CI = 0.7, 5.4 and β = -2.2-point; 95% CI = -4.9, 0.5, respectively) compared with other ages. Overall, higher blood lead concentrations were associated with elevated risk of behavior scores classified as at-risk or clinically significant on the Adaptive Skills, Behavioral Symptom Index, and Externalizing Problems scales. Contemporary levels of lead exposure during the first 8 years of life were associated with ADHD-related behaviors, specifically aggression, hyperactivity, and conduct problems. Our results highlight the importance of primary lead prevention across childhood.


Raisins, ochratoxin A and human health.
Raisins are one of the most nutritious dried fruits in the world. The occurrence of ochratoxin A (OTA) in raisins results from contamination and growth of ochratoxigenic fungi and short-term humid weather during drying. The estimation of the dietary exposure dose of OTA from raisins for the Czech population (children, adult) is presented. The risk of acute toxic effect of OTA was in the Czech Republic usually considered to be minimal. The risk of late toxic effects (particularly carcinogenic risk) after ingestion of very low single or repeated OTA doses from foodstuffs is very important.


Acceleration of indirect detection 195Pt solid-state NMR experiments by sideband selective excitation or alternative indirect sampling schemes.
The measurement of the of chemical shift (CS) tensors via solid-state NMR (ssNMR) spectroscopy has proven to be a powerful probe of structure for organic molecules, biomolecules, and inorganic materials. However, when measuring the NMR spectra of heavy spin-1/2 isotopes the chemical shift anisotropy (CSA) is commonly on the order of thousands of parts per million, which makes acquisition of NMR spectra difficult due to the low NMR sensitivity imposed by the breadth of the signals and challenges in uniformly exciting the NMR spectrum. We have recently shown that complete 195Pt NMR spectra could be rapidly measured by using 195Pt saturation or excitation selective long pulses (SLP) with multiple rotor-cycle durations and RF fields less than 50 kHz into 1H{195Pt} or 1H-31P{195Pt} PE S-RESPDOR, TONE D-HMQC-4, J-resolved, and J-HMQC pulse sequences. The SLP only provide signal or dephasing when they are applied on resonance with a spinning sideband. The magic angle spinning 195Pt NMR spectrum is reconstructed in the sideband selective NMR experiments by acquiring 1D NMR spectra at variable 195Pt pulse offsets. In this work, we present a detailed investigation of the specific pulse conditions required for the ideal performance of sideband selective experiments. Sideband selective experiments are shown to be able to accurately reproduce MAS NMR spectra with minimal distortions of relative sideband intensities. It is also demonstrated that a 195Pt NMR spectrum indirectly detected with HMQC can be rapidly obtained by acquiring a single rotor cycle of indirect dimension evolution points. We dub this method One Rotor Cycle of Acquisition (ORCA) HMQC. Sideband selective experiments and ORCA HMQC experiments are shown to provide a one order of magnitude improvement in experiment times as compared to conventional wideline HMQC experiments.


Potentiation of in vitro ara-C cytotoxicity by ribonucleotide reductase inhibitors, cyclin-dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia.
To modulate in vitro cytarabine (ara-C) resistance we combined ara-C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co-incubation of ara-C/aphidicolin showed strong synergism. The combinations of ara-C/cladribine and ara-C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara-C/flavopiridol and ara-C/UCN-01. The combination of ara-C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara-C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN-01, supporting the evaluation of these combinations in clinical trials with AML patients.


Molecular and functional characterisation of a mannose-binding lectin-like gene from Japanese sea bass (Lateolabrax japonicus).
Mannose-binding lectin (MBL) plays an important role in host immune responses against pathogens. LjMBL-like-1 was identified from Japanese sea bass (Lateolabrax japonicas), which has selectivity for galactose. Herein, this lectin might be better designated as galactose-binding lectin (LjGalBL-1). LjGalBL-1 transcripts were detected in all tested tissues, with highest expression in liver. Upon Vibrio harveyi infection, LjGalBL-1 mRNA expression was increased in major immune-related tissues, and protein levels in serum were also upregulated. Recombinant LjGalBL-1 (rLjGalBL-1) bound to monosaccharides and polysaccharides, and both rLjGalBL-1 and native LjGalBL-1 (nLjGalBL-1) agglutinated three Gram-positive bacteria (Staphylococcus aureus, Streptococcus iniae and Micrococcus luteus) and four Gram-negative bacteria (Aeromonas hydrophila, Edwardsiella tarda, Vibrio anguillarum and V. harveyi) in a Ca2+-dependent manner in vitro. Moreover, rLjGalBL-1 increased the survival rate of V. harveyi-infected fish and decreased bacterial load in liver, spleen, kidney and blood. Thus, LjGalBL-1 protects L. japonicas against V. harveyi infection.


Resection after neoadjuvant chemotherapy in advanced carcinoma of the gallbladder: a retrospective study.
Although rare over most of the world, Gallbladder cancer is very common in northern india. A delayed presentation, aggressive nature,lack of randomised trials and a poor prognosis have all contributed to the nihilistic halo encircling gallbladder cancer. None of the advances in oncology have been exploited enough to shatter the nihilistic halo. In this background we sought to analyze if the addition of neoadjuvant chemotherapy had any impact on the resectability, overall and disease free survival in patients with advanced carcinoma of the gallbladder. We reviewed the records of all patients who underwent surgery for carcinoma of the gall bladder from 2004 to 2010 at our institute retrospectively. Twenty-one patients received neoadjuvant chemotherapy and subsequently taken up for surgery. Outcome analysis of these 21 patients were done by Kaplan meier method and graphs plotted. Out of the 21 patients who were taken up for surgery after neoadjuvant chemotherapy, fourteen patients underwent R0 resection (Group 1). Seven patients had been rendered inoperable on exploration (Group 2). Thus about 66.67 % of patients deemed resectable after neoadjuvant chemotherapy on imaging underwent R0 resection. The mean overall survival of the group 1 was 42.8 months versus 6.6 months of group 2(Hazard Ratio: 3.42). Neoadjuvant chemotherapy improves resectability in some patients with unresectable gall bladder cancer. Resection after neoadjuvant chemotherapy is feasible and may improve survival in a select group of patients. However randomized studies are required to establish its definitive role.


Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance.
Extrachromosomal circular DNA was recently found to be particularly abundant in multiple human cancer cells, although its frequency varies among different tumor types. Elevated levels of extrachromosomal circular DNA have been considered an effective biomarker of cancer pathogenesis. Multiple reports have demonstrated that the amplification of oncogenes and therapeutic resistance genes located on extrachromosomal DNA is a frequent event that drives intratumoral genetic heterogeneity and provides a potential evolutionary advantage. This review highlights the current understanding of the extrachromosomal circular DNA present in the tissues and circulation of patients with advanced cancers and provides a detailed discussion of their substantial roles in tumor regulation. Confirming the presence of cancer-related extrachromosomal circular DNA would provide a putative testing strategy for the precision diagnosis and treatment of human malignancies in clinical practice.


Some acute and long-term effects of exposure in welding and thermal-cutting operations in Nigeria.
The analysis of welding fumes has shown that toxic gases are present that are irritating to the respiratory system; these gases include nitrogen dioxide and ozone, as well as the oxides of cobalt and chromium. The acute and long-term effects of exposure are assessed in the context of a welding and metal plant in Nigeria. Evidence of long-term respiratory impairment and potential lung cancer was found.


Designing an effective counteradvertising campaign--Arizona.
In this report, the authors describe an innovative antitobacco advertising campaign in Arizona that was aimed at youth. The campaign utilizes traditional as well as non-traditional methods of research to determine the attitudes, behavior and values of today's adolescents. These creative methodologies led to rigorously tested and well-received media strategies.


Insertion of IS2 creates a novel ampC promoter in Escherichia coli.
A class of ampC beta-lactamase-hyperproducing mutants of Escherichia coli were shown to have the insertion element IS2 inserted into the ampC promoter. The insertion of IS2 in orientation II created a novel promoter in which the -35 region and the 17 bp long spacing sequence between the two consensus sequences are present in IS2 DNA, whereas the -10 region from the original ampC promoter is retained. In vitro transcription revealed that the transcription initiation site in the ampC::IS2 mutants was identical with that of ampC wild-type promoter. The novel promoter exhibited a 20-fold increase in promoter strength relative to the original ampC promoter, presumably due to the increase in the spacing sequence from 16 to 17 bp. The evolution of transposable elements and of control elements such as promoters are discussed on the basis of the findings described herein.


Only four days of quadruple therapy can effectively cure Helicobacter pylori infection.
To determine whether 4 days of quadruple therapy using bismuth, tetracycline and metronidazole combined with omeprazole is effective treatment for Helicobacter pylori infection. Non-ulcer dyspepsia, as well as chronic peptic ulcer patients with biopsy-proven H. pylori infection received 4 days of quadruple therapy. They were pretreated with 3 days of omeprazole. At least 5-6 weeks later, endoscopy was repeated with 10 biopsies for urease test, histology and culture to establish cure of infection. None of the 54 patients included was lost to follow-up but two had a 14C-urea breath test instead of endoscopy. Side-effects did not interfere with compliance. Forty-nine out of 54 patients (91%; 95% CI: 80-97%) were cured. Metronidazole susceptibility data were available from 43 pre-treatment isolates. Of these 38/40 (95%) with a metronidazole-sensitive strain, and one of three with a metronidazole-resistant strain were cured. Four days of quadruple therapy after omeprazole pre-treatment is a feasible, well tolerated, and effective treatment for H. pylori infection, especially in those carrying a metronidazole-sensitive strain. It seems that in quadruple therapy, cure rate and treatment duration have a non-linear relation. Our results need confirmation, but for patients suffering from side-effects with the 7-day regimen stopping treatment after 4 days is justified.


Inflammatory Bowel Disease in the Older Adult.
Although management of inflammatory bowel disease follows a similar approach for all adults, there are certain characteristics making its treatment more challenging in older patients. The advent of novel medical treatments has changed the paradigm of inflammatory bowel disease, with an increasing focus on preventing disease progression in addition to controlling symptoms. The safety of these therapies in the elderly needs to be considered. Management of inflammatory bowel disease in the elderly is confounded by comorbidities that can increase the risk of medication or surgical complications; polypharmacy and altered pharmacokinetics also increase the risk of drug-drug interactions and adverse events.


Multifocal bullous emphysema with concurrent bronchial hypoplasia in two aged Afghan hounds.
Multiple scattered foci of bullous emphysema were detected in the lungs of two aged Afghan Hounds. The affected parenchyma contained bronchi with rudimentary cartilage and small smooth muscle bundles. The bronchi were generally lined by cuboidal epithelium. The animals were generally asymptomatic throughout their entire lives. One, the female, developed dyspnoea and tachypnoea terminally, following the rupture of two bullae.


A case report of SPG11 mutations in a Chinese ARHSP-TCC family.
Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a complicated form of hereditary spastic paraplegia, characterized by progressive spastic paraplegia, weakness of the lower extremities and is usually accompanied by mental retardation. Mutations in the Spastic Paraplegia gene 11 (SPG11) account for a large proportion of ARHSP-TCC cases worldwide. We describe a Chinese family with ARHSP-TCC. Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. We performed detailed physical and auxiliary examinations and were able to exclude acquired causes of spastic paraplegia. To determine the causative mutation, we took a candidate gene approach and screened the coding sequence and some flanking intronic sequence of SPG11 by direct Sanger sequencing. We identified two novel compound heterozygous mutations in SPG11 in affected individuals (c.1551_1552delTT, p.Cys518SerfsTer39 and c.5867-1G > T (IVS30-1G > T), p.Thr1956ArgfsTer15). Bioinformatic analysis predicts that these mutations would lead to a loss of protein function due to the truncation of the SPG11 protein. The results of this case report indicate a broader approach to include screening for SPG11 mutations in ARHSP-TCC patients. Our findings enrich the phenotypic spectrum of SPG11 mutations.


Helicobacter pylori "rescue" therapy after failure of two eradication treatments.
Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face Helicobacter pylori treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final--overall--eradication rate. After failure of a combination of proton pump inhibitor (PPI), amoxicillin, and clarithromycin, the use of empirical quadruple therapy (PPI-bismuth-tetracycline-metronidazole), has been generally used as the optimal second-line therapy. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given. It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximize H. pylori eradication, based on the different possibilities of empirical treatment (when antibiotic susceptibilities are unknown). Thus, if one does not want to perform culture before the administration of the third treatment after failure of the first two, different empirical treatments exist, including regimens based on: 1, amoxicillin (amoxicillin-PPI at high doses); 2, amoxicillin plus tetracycline (PPI-bismuth-tetracycline-amoxicillin, or ranitidine-bismuth-citrate-tetracyline-amoxicillin); 3, rifabutin (rifabutin-amoxicillin-PPI); 4, levofloxacin (levofloxacin-amoxicillin-PPI); and 5, furazolidone (furazolidone-bismuth-tetracycline-PPI).


Improving access to quality clinical nurse teaching--a partnership between Australia and Vietnam.
Until recently, standards to guide nursing education and practice in Vietnam were nonexistent. This paper describes the development and implementation of a clinical teaching capacity building project piloted in Hanoi, Vietnam. The project was part of a multi-component capacity building program designed to improve nurse education in Vietnam. Objectives of the project were to develop a collaborative clinically-based teaching model that encourages evidence-based, student-centred clinical learning. The model incorporated strategies to promote development of nursing practice to meet national competency standards. Thirty nurse teachers from two organisations in Hanoi participated in the program. These participants attended three workshops, and completed applied assessments, where participants implemented concepts from each workshop. The assessment tasks were planning, implementing and evaluating clinical teaching. On completion of the workshops, twenty participants undertook a study tour in Australia to refine the teaching model and develop an action plan for model implementation in both organisations, with an aim to disseminate the model across Vietnam. Significant changes accredited to this project have been noted on an individual and organisational level. Dissemination of this clinical teaching model has commenced in Ho Chi Minh, with further plans for more in-depth dissemination to occur throughout the country.


Cross-Cultural Adaptation and Psychometric Evaluation of the Neonatal Eating Assessment Tool-Breastfeeding Into Tamil.
To adapt the Neonatal Eating Assessment Tool-Breastfeeding (NeoEAT-Breastfeeding) into Tamil, a language spoken in several South Asian countries, to identify the tool's factor structure, and to assess its psychometric properties. Cross-sectional. Tertiary care hospital in South India. A cohort of 323 mothers of infants ages 1 week to 7 months, including infants with and without feeding difficulties. To adapt the English tool to Tamil, we followed standard procedures specified by the tool developers and international guidelines for tool translation and adaptation, including pilot testing and personal interviews with participants who had infants younger than 7 months. Participants completed the NeoEAT-Breastfeeding (Tamil) after assessment of breastfeeding by professionals. The 62-item tool involves rating each item on a 6-point scale, and higher scores indicate increased feeding difficulties. After exploratory factor analysis, we divided the tool into five subscales in the Tamil version compared to the seven subscales in the original English version. The Tamil version demonstrated high internal consistency reliability (Cronbach's α = 0.97) and test-retest reliability (intraclass correlation = 0.99) for the total scores. Infants with feeding concerns demonstrated significantly higher total and subscale scores on the NeoEAT-Breastfeeding (Tamil) than infants without feeding concerns (p = .000; construct validity). The NeoEAT-Breastfeeding (Tamil) holds promise as a culturally appropriate, clinically useful parent-report tool with evidence for initial reliability and validity for identifying feeding-related concerns among infants younger than 7 months in the Tamil-speaking population.


Quantum Dot-Based Probes for Labeling and Imaging of Cells that Express Matrix Metalloproteinases.
The practical synthesis of novel multivalent fluorescent quantum-dot-based probes to target cellular matrix metalloproteinases (MMPs) (MT-MMPs) is reported. We show that these probes, which are decorated with a nanomolar water-soluble MMP inhibitor, can be used to label preferentially the surface of cancer cells that are known to express MMPs while no binding was observed on cells that do not.


Plant fructose-1,6-bisphosphatases: characteristics and properties.
In this minireview the properties and characteristics of plant fructose-1,6-bisphosphatases (D-fructose-1,6-bisphosphatase 1-phosphohydrolase, EC 220.127.116.11) are discussed. The properties and characteristics of the chloroplastic and cytoplasmic forms of the enzyme are reviewed. For purposes of comparison some reference is made to fructose-1,6-bisphosphatases from other species.


Health status after total wrist arthrodesis for posttraumatic arthritis.
Total wrist arthrodesis is regarded as the most predictable way to relieve the pain of posttraumatic wrist arthritis. Wrist arthrodesis also is believed to be compatible with a high level of upper-extremity function. This study evaluated the effect of total wrist arthrodesis on both general and upper-extremity-specific health status in patients treated for posttraumatic wrist arthritis. By using an institutional review board-approved protocol 22 patients were evaluated an average of 6 years after total wrist arthrodesis for posttraumatic arthritis. Upper-extremity-specific and general health status were measured using the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short-Form 36 (SF-36) instruments, respectively. Patient satisfaction and interest in pursuing a wrist-mobilizing procedure should one become available also were assessed. Objective assessment included grip strength, digit range of motion, and radiographic fusion. Grip strength averaged 79% of the uninvolved wrist. The average Disabilities of the Arm, Shoulder, and Hand questionnaire score was 25. The average physical component score of the Short-Form 36 was 39 and the average mental component score was 52. Fourteen patients complained of wrist pain, including severe pain in 4 patients. Fifteen patients were satisfied or very satisfied with the result of the fusion, 5 patients were neutral, and 2 patients were mildly dissatisfied. Twenty patients would elect to have a procedure that could make their wrist move again if one were available. Substantial dysfunction was noted on both upper-extremity-specific and general health status measures after total wrist arthrodesis for posttraumatic conditions. Pain was improved but not eliminated.


Complement profile and activation mechanisms by different LDL apheresis systems.
Extracorporeal removal of low-density lipoprotein (LDL) cholesterol by means of selective LDL apheresis is indicated in otherwise uncontrolled familial hypercholesterolemia. During blood-biomaterial interaction other constituents than the LDL particles are affected, including the complement system. We set up an ex vivo model in which human whole blood was passed through an LDL apheresis system with one of three different apheresis columns: whole blood adsorption, plasma adsorption and plasma filtration. The concentrations of complement activation products revealed distinctly different patterns of activation and adsorption by the different systems. Evaluated as the final common terminal complement complex (TCC) the whole blood system was inert, in contrast to the plasma systems, which generated substantial and equal amounts of TCC. Initial classical pathway activation was revealed equally for both plasma systems as increases in the C1rs-C1inh complex and C4d. Alternative pathway activation (Bb) was most pronounced for the plasma adsorption system. Although the anaphylatoxins (C3a and C5a) were equally generated by the two plasma separation systems, they were efficiently adsorbed to the plasma adsorption column before the "outlet", whereas they were left free in the plasma in the filtration system. Consequently, during blood-biomaterial interaction in LDL apheresis the complement system is modulated in different manners depending on the device composition.


Canrenoate disposition in dogs. Tissue distribution and elimination.
The metabolism and tissue distribution of intravenously administered C14-canrenoate-potassium (CR-K) was studied at various time intervals in 10 dogs. After a rapid decline of total radioactivity immediately after injection, the elimination in plasma occurred in two distinct phases with half-lives of 6.8 and 23.6 h. Canrenoate was rapidly converted to lipid- and water-soluble metabolites which were separated by thin-layer chromatography. Most tissues showed similar concentrations of total radioactivity as plasma. An accumulation of radioactivity per g wet weight was detected in the adrenal glands and fat tissue as well as in the metabolic and excretory organs but not in the heart. Taking into consideration that skeletal muscle, fat tissue and liver constitute about 64% of the body weight, it is obvious that the main part of total radioactivity was present in these tissues. In contrast to plasma, urine and feces, where various metabolites could be analysed, the bulk of radioactivity in tissues is represented by canrenone. Thus, the estimation of the parent compound and its metabolites in plasma, urine and feces does not allow final conclusions about the active substance in various tissues. Within 72 h 47% of the dose was recovered in urine and 49% in feces.


Therapeutic intervention with virtual reality in patients with Parkinson's disease for upper limb motor training: A systematic review.
To analyze the scientific evidence regarding changes in upper extremities in patients with Parkinson's disease who use virtual reality as part of their neurological rehabilitation treatment. The search was carried out in the following databases: MEDLINE, Cochrane Library, PEDROs and SCOPUS. The following inclusion criteria were applied to a total of 106 articles: Randomized clinical trials with an age of 5 years, the sample had to be of patients with PD (regardless of their state of involvement) and who had performed RV in the treatment of limbs superiors. A total of n=7 articles were used, in which the variables corresponding to upper limb motor control were measured, such as: fine motor dexterity, gross motor dexterity, strength, tremor, functionality and speed. Virtual Reality as tool in neurorehabilitation in patients with Parkinson's disease shows positive effects in all measurements related to upper limb motor control.


Plasma fibrin clot proteomics in patients with acute pulmonary embolism: Association with clot properties.
It has been reported that 476 proteins can be detected in plasma fibrin clots from patients with venous thromboembolism. Plasma fibrin clots proteomic composition in relation to their properties has not been studied in acute pulmonary embolism (PE). Clots generated from plasma of 20 PE patients and 20 healthy controls were assessed using mass spectrometry, clot permeability (Ks), and clot lysis time (CLT). The proteomic composition of plasma fibrin clots from acute PE patients differed from that of control subjects in regard to 198 clot-bound proteins. In the acute PE group, we observed increased clot-bound fibrinogen, apolipoprotein B-100, platelet glycoprotein Ib, lipopolysaccharide-binding protein, and histones H3 + 4 and reduced fibronectin, α2-antiplasmin, α2-macroglobulin, factor (F)XIII, histidine-rich glycoprotein, antithrombin, von Willebrand Factor, plasminogen, and prothrombin. Among PE patients, low Ks (≤3.83 × 10-9 cm2) was associated with increased clot-bound C-reactive protein, kininogen-1, protein S, β-2-microglobulin, and thromboxane-A synthase when compared with patients having Ks > 3.83 × 10-9 cm2. Ks correlated inversely with FIX and FV, thrombin-activatable fibrinolysis inhibitor, complement C1s, C7, C8, and apolipoprotein A-I. The specific protein composition in plasma fibrin clots from acute PE patients is associated with denser clot formation. Several proteins unrelated to the coagulation system can modulate fibrin phenotype in acute thrombotic states. SIGNIFICANCE: Our study significantly advances the field of thrombosis and hemostasis. The plasma fibrin clot proteomics findings fill the gap of knowledge about the presence and the role of other proteins to the plasma fibrin clot in the acute phase of pulmonary embolism, aside fibrinogen, which is the main component of fibrin. The reported methodology, which involves the sample preparation using Multienzyme Digestion-Filter Aided Sample Preparation (MED FASP), data acquisition with the Quadrupole-Orbitrap mass spectrometer, and data analysis using the advanced tools such as MaxQuant, Total Protein Approach and Perseus, allows to gain not only the qualitative, but also the quantitative insights into the microworld of proteins entangled among the fibrin network. By comparing the clots formed from plasma of patients with acute pulmonary embolism with the clots from healthy control, we provide the specific protein composition associated with unfavorable clot properties observed in this disease. Moreover, our findings emphasize that several proteins unrelated to the coagulation system, can modulate fibrin phenotype in acute thrombotic states.


Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients.
Disturbances in dopaminergic transmission have been implicated in the etiology of psychotic disorders. Interindividual differences in deoxyribonucleic acid (DNA) sequences coding for dopamine receptor proteins might contribute to the genetic background of these diseases. We have identified a variation in exon 1 of the dopamine D4 receptor (DRD4) gene, which is characterized by a polymorphic 12 base pair (bp) repeat. This repeat codes for a sequence of four amino acids in the extracellular N-terminal part of the receptor, which borders the first putative transmembrane domain. The 12bp repeat occurs as a two-fold repeat in the more common variant (A1 allele) and is represented only once in the rarer one (A2 allele). The frequency of this DNA polymorphism was determined in a sample of 59 patients suffering from delusional disorder, in 79 schizophrenic patients, and in 75 control subjects. Sixteen (27%) of the 59 patients with delusional disorder carried the A2 allele compared with six (8%) of the controls. The observed difference in genotype frequencies between patients with delusional disorder and controls was highly significant. There were no significant differences in genotype frequencies between schizophrenics and controls: Our results strongly suggest the involvement of genetic variation in the DRD4 gene in conferring susceptibility to delusional disorder.


Characterization and removal efficiencies of microplastics discharged from sewage treatment plants in Southeast Spain.
Microplastics (MPs) are ubiquitous pollutants that can effectively harm different ecosystems. The information on the relative contribution of wastewater treatment plants (WWTPs) to the surrounding environment is important, in order to understand ecological health risks and implement measures to reduce their presence. This focus article presents a quantitative assessment on the relative concentration and types of MPs delivered from four WWTPs located at the Southeast of Spain. Samples from WWTPs were collected throughout a four-year period, comprising more than 1,200 L of analyzed wastewater and 3,215 microparticles isolated. Density extraction with 1.08 g/mL NaCl salt solution was systematically used as the main separation method, in a simple and reliable manner, and repeat extraction cycles did not play any significant impact on the study outcomes. The four WWTPs had removal efficiencies between 64.3% and 89.2% after primary, secondary, and tertiary treatment phases, without diurnal or daily variations. Advanced treatment methods displayed a lower removal rate for fibers than for particulate MPs. The abundance of MPs was always higher and with a lower mean size in wastewater samples collected in Autumn than for the rest of seasons. MPs dumped from WWTPs in large quantities into the environment are meant to be regarded as an important point source for aquatic and terrestrial environments.


Somatic evoked potential evaluation of cerebral status in Reye syndrome.
Median nerve somatic evoked potentials (SEPs) were serially recorded in 12 Reye syndrome patients from shortly after admission to discharge. Recovery was clinically satisfactory in nine, unsatisfactory in two, and one died. All SEP components were absent or markedly depressed in initial recordings. Early progressive recovery of primary cortical components was associated with patient survival; lack of it was associated with death. Progressive recovery of SEP components later than 100 msec was associated with satisfactory clinical recovery; failure of recovery of these components was associated with residual neuropsychological deficit. Evaluation of late component recovery required comparison with age-dependent SEP configurations in normal children which differ from adults. We conclude that serial SEP recording is of significant value and superior to the EEG in early prognosis for survival, prognosis for clinically satisfactory or unsatisfactory recovery, and general evaluation of neurologic status in Reye syndrome.


Abortion at 12 or more weeks' gestation and travel for later abortion care among Mississippi residents.
To assess the association between indicators of economic disadvantage and geographic accessibility of reproductive health services and abortions ≥ 12 weeks' gestation in Mississippi. This cross-sectional study used data on Mississippi residents who obtained abortion care from 12 of 14 facilities in Mississippi, Alabama, Louisiana, and Tennessee in 2018. We estimated logistic regression models to assess the association between levels of county deprivation, the number of obstetrician and/or gynecologists per 10,000 women, and one way distance to the nearest facility with having an abortion ≥ 12 weeks' gestation. We compared the median one-way distance to the facility where patients < 12 weeks', 12-15 weeks', and ≥ 16 weeks' gestation received care, using Kruskal-Wallis tests. Of the 4,455 Mississippi residents who obtained abortions, 73% were Black, 59% lived ≥ 50 miles from a facility, and 60% obtained care in Mississippi. Overall, 764 (17.2%) abortions were performed ≥ 12 weeks' gestation. In adjusted models, those in counties with moderate (OR, 1.47; 95% CI: 1.15-1.90) and high (OR: 1.36, 95% CI: 1.01-1.83) (vs low) levels of economic deprivation and counties with 0.1-1.4 (vs ≥ 2.5) obstetrician/gynecologists per 10,000 women (OR: 1.55; 95% CI: 1.06-2.27) had higher odds of obtaining an abortion ≥12 weeks' gestation. Mississippi residents who obtained abortions ≥ 16 weeks' gestation traveled a median 143 miles one way to the facility where they received care, compared to 69 miles and 60 miles traveled by those < 12 weeks' and 12-15 weeks' gestation, respectively (p < .001). Many Mississippi residents obtained abortion care ≥ 12 weeks' gestation, which is related to greater economic constraints and limited geographic access to reproductive health services. People's need for abortions ≥ 12 weeks' gestation may be higher in communities with limited access to reproductive health services and among those living in areas with greater economic disadvantage. State laws that narrow gestational limits would increase long-distance travel for later abortion care, and disproportionately affect those with fewer resources.


Potential CRF1R PET imaging agents: 1-fluoroalkylsubstituted 5-halo-3-(arylamino)pyrazin-2(1H)-ones.
A series of pyrazinones were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients are discussed herein.


Morphology of the rat carotid sinus nerve. I. Course, connections, dimensions and ultrastructure.
An analysis of the morphology of the carotid sinus nerve in 39 rats revealed that the nerve emerged from the glossopharyngeal nerve (nerve IX) 0.6-1.0 mm beyond the distal extent of the petrosal ganglion. In 68% of cases the nerve consisted of a single bundle of axons; two bundles were present in the other nerves. Near the rostral pole of the carotid body, the nerve divided into multiple bundles of axons. Most axon bundles entered the carotid body, but some instead joined sympathetic nerves from the superior cervical ganglion. Some of the latter group of sinus nerve axons innervated the wall of the carotid sinus. Other presumptive baroreceptor axons reached the carotid sinus from the sinus nerve by first traversing the carotid body. The sinus nerve had an average length of 2.0 +/- 0.13 mm (mean +/- S.E.M., range = 1.3-2.9 mm, N = 15) and was elliptical in cross-section (major axis = 77 microns, minor axis = 46 microns). The nerve contained an average of 625 axons, 86% of which were unmyelinated. The perineurial sheath that enveloped the circumference of the nerve was comprised of 3 or 4 layers of cells interconnected by gap junctions and tight junctions. Near the carotid body, the perineurium extended into the nerve where it compartmentalized fascicles of axons. The endoneurium consisted mainly of collagenous fibres (mean diameter 40 nm) that were only half the size of those outside the perineurium. Endoneurial connective tissue cells were sparse, being only 5% as numerous as Schwann cells. The one blood vessel in the nerve (mean luminal diameter 12.4 +/- 1.2 microns) usually arose from vessels in nerve IX and terminated in a venule at the rostral surface of the carotid body. Ganglion cells were located in nerve IX near the origin of the sinus nerve and along the length of the sinus nerve itself. All ganglion cells examined were postsynaptic to vesicle-containing nerve terminals, and therefore were presumed to be autonomic rather than sensory. Ganglion cells were more numerous in terminal branches of the sinus nerve on the ventral surface of the carotid body. Most other ganglion cells in the carotid body were located among axons of the ganglioglomerular nerve, although some were associated with a small branch of the vagus nerve. Paraganglia were located within the sinus nerve in 15% of cases, and in another 10% of cases they were found nearby in nerve IX. The paraganglia, which measured approximately 50 X 50 X 100 microns, were innervated by axons that resembled sensory nerves of the carotid body.


Influence of nationwide policy on citizens' awareness and willingness to perform bystander cardiopulmonary resuscitation.
Public awareness to cardiopulmonary resuscitation (CPR) and cardiac arrest is influenced by systemic factors including related policies and legislations in the community. Here, we describe and compare the results of the two nationwide CPR surveys in 2007 and 2011 examining public awareness and attitudes to bystander CPR in South Korea along with changes in nationwide CPR policies and systemic factors. This population-based study used specially designed questionnaires via telephone surveys. We conducted bi-temporal surveys by stratified cluster sampling to assess the impact of age, gender, and geographic regions in 2007 (n=1029) and in 2011 (n=1000). Logistic regression analysis was performed to identify factors associated with willingness to perform bystander CPR. Public awareness of automated external defibrillators increased from 3.0% in 2007 to 32.6% in 2011. The proportion of the population that underwent CPR training within the previous 2 years increased significantly from 26.9% to 49.0%. The factors most related with intention of bystander CPR were male gender, younger age, CPR awareness, recent CPR training, and qualified CPR learning. In 2011, 75.8% of respondents were more willing to perform bystander CPR for stranger vs. 68.3% in 2007 (p=0.002). Additional dispatcher hands-only CPR increased this proportion (85.8%, p<0.001). However, bystander CPR experience rates remained unchanged (3.6-3.9%). Changes in nationwide CPR policies and systemic factors affected citizens' awareness and willingness to perform bystander CPR. Additionally, applied dispatcher hands-only CPR and publicity increased public willingness to perform bystander CPR.


Comparative genomic hybridization using DNA from laser capture microdissected tissue.
Comparative genomic hybridization (CGH) is a powerful screening technique that can identify regions of gain and loss within the whole genome in a single experiment. The combination of laser capture microdissection, whole-genome amplification, and CGH permits genomic screening with high specificity and sensitivity. This complement of techniques has enabled analysis of focal regions and subpopulations of cells within a tissue, which has previously been difficult, providing insight into disease progression and heterogeneity. This chapter outlines the techniques involved in producing labeled probes from DNA extracted from laser capture microdissected material and the methods for hybridization of these probes to metaphase chromosomes. This protocol can also be applied to the preparation of probes for CGH arrays.


Prediction of impacts of mutations on protein structure and interactions: SDM, a statistical approach, and mCSM, using machine learning.
Next-generation sequencing methods have not only allowed an understanding of genome sequence variation during the evolution of organisms but have also provided invaluable information about genetic variants in inherited disease and the emergence of resistance to drugs in cancers and infectious disease. A challenge is to distinguish mutations that are drivers of disease or drug resistance, from passengers that are neutral or even selectively advantageous to the organism. This requires an understanding of impacts of missense mutations in gene expression and regulation, and on the disruption of protein function by modulating protein stability or disturbing interactions with proteins, nucleic acids, small molecule ligands, and other biological molecules. Experimental approaches to understanding differences between wild-type and mutant proteins are most accurate but are also time-consuming and costly. Computational tools used to predict the impacts of mutations can provide useful information more quickly. Here, we focus on two widely used structure-based approaches, originally developed in the Blundell lab: site-directed mutator (SDM), a statistical approach to analyze amino acid substitutions, and mutation cutoff scanning matrix (mCSM), which uses graph-based signatures to represent the wild-type structural environment and machine learning to predict the effect of mutations on protein stability. Here, we describe DUET that uses machine learning to combine the two approaches. We discuss briefly the development of mCSM for understanding the impacts of mutations on interfaces with other proteins, nucleic acids, and ligands, and we exemplify the wide application of these approaches to understand human genetic disorders and drug resistance mutations relevant to cancer and mycobacterial infections. STATEMENT FOR A BROADER AUDIENCE: Genetic or somatic changes in genes can lead to mutations in human proteins, which give rise to genetic disorders or cancer, or to genes of pathogens leading to drug resistance. Computer software described here, using statistical approaches or machine learning, uses the information from genome sequencing of humans and pathogens, together with experimental or modeled 3D structures of gene products, the proteins, to predict impacts of mutations in genetic disease, cancer and drug resistance.


Purification and characterization of an endo-xylanase from Trichoderma sp., with xylobiose as the main product from xylan hydrolysis.
Fungal endo-β-1,4-xylanases (endo-xylanases) can hydrolyze xylan into xylooligosaccharides (XOS), and have potential biotechnological applications for the exploitation of natural renewable polysaccharides. In the current study, we aimed to screen and characterize an efficient fungal endo-xylanase from 100 natural humus-rich soil samples collected in Guizhou Province, China, using extracted sugarcane bagasse xylan (SBX) as the sole carbon source. Initially, 182 fungal isolates producing xylanases were selected, among which Trichoderma sp. strain TP3-36 was identified as showing the highest xylanase activity of 295 U/mL with xylobiose (X2) as the main product when beechwood xylan was used as substrate. Subsequently, a glycoside hydrolase family 11 endo-xylanase, TXyn11A, was purified from strain TP3-36, and its optimal pH and temperature for activity against beechwood xylan were identified to be 5.0 and 55 °C, respectively. TXyn11A was stable across a broad pH range (3.0-10.0), and exhibited strict substrate specificity, including xylan from beechwood, wheat, rye, and sugarcane bagasse, with Km and Vmax values of 5 mg/mL and 1250 μmol/mg min, respectively, toward beechwood xylan. Intriguingly, the main product obtained from hydrolysis of beechwood xylan by TXyn11A was xylobiose, whereas SBX hydrolysis resulted in both X2 and xylotriose. Overall, these characteristics of the endo-xylanase TXyn11A indicate several potential industrial applications.


Deep sequencing reveals exceptional diversity and modes of transmission for bacterial sponge symbionts.
Marine sponges contain complex bacterial communities of considerable ecological and biotechnological importance, with many of these organisms postulated to be specific to sponge hosts. Testing this hypothesis in light of the recent discovery of the rare microbial biosphere, we investigated three Australian sponges by massively parallel 16S rRNA gene tag pyrosequencing. Here we show bacterial diversity that is unparalleled in an invertebrate host, with more than 250,000 sponge-derived sequence tags being assigned to 23 bacterial phyla and revealing up to 2996 operational taxonomic units (95% sequence similarity) per sponge species. Of the 33 previously described 'sponge-specific' clusters that were detected in this study, 48% were found exclusively in adults and larvae - implying vertical transmission of these groups. The remaining taxa, including 'Poribacteria', were also found at very low abundance among the 135,000 tags retrieved from surrounding seawater. Thus, members of the rare seawater biosphere may serve as seed organisms for widely occurring symbiont populations in sponges and their host association might have evolved much more recently than previously thought.


Highly elevated levels of prostaglandin D synthase in the serum of patients with renal failure.
To investigate whether prostaglandin D (PGD) synthase levels differ in the serum of patients with or without renal dysfunction. PGD synthase or beta-trace protein is a major constituent (approximately 3% of total protein) of human cerebrospinal fluid (CSF). We previously reported that PGD synthase levels in serum are approximately 40- to 60-fold lower than those in CSF. We measured the PGD synthase concentration in various sera with a highly sensitive and specific immunofluorometric assay along with the serum creatinine level. Analysis for PGD synthase and creatinine was performed in 30 sera from non-renal failure subjects, in 7 sera from patients treated with continuous ambulatory peritoneal dialysis, and in 34 sera that were before and after hemodialysis samples from 17 patients with renal failure. Elevated creatinine concentration was observed in patients with renal insufficiency, as expected (Mann-Whitney P < 0.0001; chi-square P < 0.0001 ). We found that serum PGD synthase concentration from patients with renal failure is significantly elevated compared with the serum PGD synthase concentration from non-renal failure subjects (Mann-Whitney P < 0.0001; chi-square P < 0.0001). Approximately a 35-fold increase of serum PGD synthase is observed for patients with renal failure compared with non-renal failure subjects. Serum PGD synthase concentration is not affected by hemodialysis in acute renal failure patients (Mann-Whitney P = 0.918), unlike serum creatinine levels, which were decreased significantly after hemodialysis (Mann-Whitney P = 0.0001). We conclude that renal impairment is highly associated with elevated serum PGD synthase levels. Measurement of PGD synthase in serum is a new biochemical marker of renal insufficiency.


The evolution of maximum terrestrial body mass in sauropod dinosaurs.
The long-necked dinosaurs, sauropods, are famous for their extreme body sizes, evolving body masses several times greater than the next-heaviest terrestrial animals, elephant-like and rhinoceros- like mammals and 'duck-billed' dinosaurs. The pace of sauropod discovery has been exponential in recent decades, resulting in the recognition of sauropods as a global, ecologically diverse group of herbivorous dinosaurs comprising over 250 known species1. However, limitations due to missing data from their patchy fossil record have so far limited studies of sauropod body-size evolution to less than half their known diversity1. Here, I present models to confidently predict unknown limb-bone measurements in sauropods, resulting in a dataset 50% larger than previously assembled. Leveraging the emerging consilience among body mass estimation methods for fossil tetrapods, I then map sauropod body mass evolution through time in a phylogenetic context. Likelihood-based ancestral state reconstruction reveals that sauropods convergently surpassed maximum terrestrial mammalian body mass at least three dozen times over the course of 100 million years, on at least six landmasses and in at least five ecomorphologically disparate clades. Sauropod maximum body mass rapidly increased early in their evolutionary history from under 5,000 kg before levelling off around 40,000 kg (with notable exceptions)2, in a pattern similar to that observed in terrestrial mammals3.


Patient tolerance to carbonic anhydrase inhibitors.
We evaluated carbonic anhydrase inhibitors in a crossover study with a placebo and random allocation of treatment administration. Drugs evaluated included acetazolamide tablets and Sequels, dichlorphenamide, ethoxzolamide, methazolamide, and an ascorbic acid placebo. The best tolerated drug was acetazolamide Sequels. Methazolamide was next. The least tolerated drugs were ethoxzolamide, acetazolamide tablets, and dichlorphenamide.


Effect of glutamine synthesis inhibition with methionine sulfoximine on the nitric oxide-cyclic GMP pathway in the rat striatum treated acutely with ammonia: a microdialysis study.
Ammonia neurotoxicity is associated with overactivation of N-methyl-D-aspartate (NMDA) receptors leading to enhanced nitric oxide and cyclic GMP synthesis and to accumulation of reactive oxygen and nitrogen species. Ammonia is detoxified in the brain via synthesis of glutamine, which if accumulated in excess contributes to astrocytic swelling, mitochondrial dysfunction and cerebral edema. This study was aimed at testing the hypothesis that the activity of the NMDA/NO/cGMP pathway is controlled by the ammonia-induced production of Gln in the brain. Ammonium chloride (final concentration 5 mM), infused for 40 min to the rat striatum via a microdialysis probe, caused a significant increase in Gln (by 40%), NO oxidation products (nitrite+nitrate=NOx) (by 35%) and cGMP (by 50%) concentration in the microdialysate. A Gln synthetase inhibitor, methionine sulfoximine (MSO, 5 mM), added directly to the microdialysate, completely prevented ammonia-mediated production of Gln, and paradoxically, it increased ammonia-mediated production of NOx and cGMP by 230% and 250%, respectively. Of note, MSO given alone significantly reduced basal Gln concentration in the rat striatum, had no effect on the basal NOx concentration, and attenuated basal concentration of cGMP in the microdialysate by 50%. The results of the present study suggest that Gln, at physiological concentrations, may ameliorate excessive activation of the NO-cGMP pathway by neurotoxic concentrations of ammonia. However, in view of potential direct interference of MSO with the pathway, exogenously added Gln and less toxic modulators of Gln content and/or transport will have to be employed in further studies on the underlying mechanisms.


Viral ribonucleotide reductase attenuates the anti-herpes activity of acyclovir in contrast to amenamevir.
Amenamevir is a helicase-primase inhibitor of herpes simplex virus (HSV) and varicella-zoster virus (VZV) and is used for the treatment of herpes zoster in Japan. The half maximal effective concentrations (EC50s) of acyclovir and sorivudine for VZV increased as the time of treatment was delayed from 6 to 18 h after infection, while those of amenamevir and foscarnet were not affected. Susceptibility of infected cells at 0 and 18 h after infection was examined with four anti-herpes drugs, and the fold increases in EC50 for acyclovir, sorivudine, amenamevir, and foscarnet were 13.1, 6.3, 1.3, and 1.0, respectively. The increase in the EC50s for acyclovir in the late phase of infection in VZV and HSV was abolished by hydroxyurea, a ribonucleotide reductase (RR) inhibitor. The common mechanism affecting antiviral activities of acyclovir to HSV and VZV was examined in HSV-infected cells. The amount of HSV DNA in cells treated with amenamevir at 10 x EC50 was similar at 0 and 12 h but less than that in cells treated with acyclovir at 10 x EC50. dGTP, produced through viral RR, peaked at 4 h and decreased thereafter as it was consumed by viral DNA synthesis. Because acyclovir and amenamevir inhibited viral DNA synthesis, thus making dGTP unnecessary, dGTP was significantly more abundant in the presence of acyclovir and amenamevir than in untreated, infected cells. Abundant dGTP supplied by RR may compete with acyclovir triphosphate and attenuate its antiviral activity. In contrast, abundant dGTP did not influence the inhibitory action of amenamevir on viral helicase-primase activity. ATP was significantly decreased at 12 h after infection and significantly more abundant in untreated infected cells compared to cells treated with acyclovir and amenamevir. The anti-herpetic activity of amenamevir was not affected by the replication cycle of VZV and HSV, indicating the suitability of amenamevir for the treatment of herpes zoster and suppressive therapy for genital herpes.


A temporal bone preparation for the study of cochlear micromechanics at the cellular level.
An in vitro preparation of the guinea pig temporal bone was developed for studying the micromechanical behaviour of the cochlea. The preparation consists of the cochlea opened at the apex, allowing observation of cellular structures within the cochlear partition with an optical sectioning microscope and measurements of cellular vibration with laser interferometry. The middle ear ossicles and the tympanic membrane are left intact as well as the bony part of the external auditory canal, which is used for delivering a sound stimulus to the cochlea.


Multiple screw fixation versus cementless bipolar hemiarthroplasty for femur neck fracture using a nationwide hip fracture registry.
Cementless bipolar hemiarthroplasty (BHA) recently gained popularity as a treatment for femur neck fracture (FNF), but there have been few studies comparing this with multiple screw fixation (MSF) in the elderly population. The purpose of this study is to compare (1) surgery-related parameters, (2) reoperation rate as a local complication, (3) in-hospital systemic complication rate, and (4) mortality rate at 1 year after MSF and cementless BHA in patients with FNF using nationwide data. Six-hundred sixty-six hips (aged ≥ 50 years) extracted from nationwide Hip Fracture Registry were included in this study (133 MSF and 533 cementless BHA). One hundred fifty-six hips were divided into nondisplaced FNF (Group A) and 510 into displaced FNF (Group B). We evaluated (1) surgery-related parameters (anesthesia type, time to surgery, operation time, estimated blood loss and volume of postoperative transfusion), (2) the rate of and reasons for reoperation, (3) the rate and type of in-hospital systemic complications and (4) one-year mortality rate after surgery. In Group A, MSF showed shorter operation time (p = 0.004) and lower incidence of in-hospital systemic complications (p = 0.003). In Group B, cementless BHA demonstrated lower reoperation rate than MSF (p < 0.001). In both Group A and B, cementless BHA was associated with higher estimated blood loss than MSF (p < 0.001). Based on findings in our study, MSF might be a more favorable option for nondisplaced FNF, whereas cementless BHA might be a better one for displaced FNF in patients older than fifty. Nevertheless, our nationwide study also showed that numbers of cementless BHAs were being performed for nondisplaced FNF even in teaching hospitals.


Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature.
After 20 years of development, there is confusion in the nomenclature of transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN). We performed a systematic review of transcutaneous stimulation of ABVN in nomenclature. A systematic search of the literature was carried out, using the bibliographic search engine PubMed. The search covered articles published up until June 11, 2020. We recorded the full nomenclature and abbreviated nomenclature same or similar to transcutaneous stimulation of ABVN in the selected eligible studies, as well as the time and author information of this nomenclature. From 261 studies, 67 full nomenclatures and 27 abbreviated nomenclatures were finally screened out, transcutaneous vagus nerve stimulation and tVNS are the most common nomenclature, accounting for 38.38% and 42.06%, respectively. In a total of 97 combinations of full nomenclatures and abbreviations, the most commonly used nomenclature for the combination of transcutaneous vagus nerve stimulation and tVNS, accounting for 30.28%. Interestingly, the combination of full nomenclatures and abbreviations is not always a one-to-one relationship, there are ten abbreviated nomenclatures corresponding to transcutaneous vagus nerve stimulation, and five full nomenclatures corresponding to tVNS. In addition, based on the analysis of the usage habits of nomenclature in 21 teams, it is found that only three teams have fixed habits, while other different teams or the same team do not always use the same nomenclature in their paper. The phenomenon of confusion in the nomenclature of transcutaneous stimulation of ABVN is obvious and shows a trend of diversity. The nomenclature of transcutaneous stimulation of ABVN needs to become more standardized in the future.


The G protein estrogen receptor (GPER) is regulated by endothelin-1 mediated signaling in cancer cells.
Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor involved in many diseases, including certain cardiovascular disorders and cancer. As previous studies have shown that the G protein estrogen receptor (GPER) may regulate ET-1 dependent effects on the vascular system, we evaluated whether GPER could contribute to the effects elicited by ET-1 in breast cancer and hepatocarcinoma cells. Here, we demonstrate that ET-1 increases GPER expression through endothelin receptor A (ETAR) and endothelin receptor B (ETBR) along with the activation of PI3K/ERK/c-Fos/AP1 transduction pathway. In addition, we show that GPER is involved in important biological responses observed upon ET-1 exposure, as the migration of the aforementioned tumor cells and the formation of tube-like structures in human umbilical vein endothelial cells (HUVECs). Our data suggest that GPER may contribute to ET-1 action toward the progression of some types of tumor.


Comparative analysis of intercellular lipid organization and composition between psoriatic and healthy stratum corneum.
The lipid composition and organization of the stratum corneum (SC) in patients with psoriasis and healthy subjects were compared using X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and ultraperformance liquid chromatography, combined with time-of-flight mass spectrometry (UPLC-TOFMS). In healthy SC (HSC), SC lipids formed two lamellar phases (long and short periodicity phases). Hexagonal and orthorhombic hydrocarbon-chain packing were observed in the lateral lipid organization at 30 °C via X-ray diffraction. In HSC, the lamellar phases and the hydrocarbon-chain packing organizations changed with elevated temperatures and finally disappeared. In these behaviors, the high-temperature hexagonal hydrocarbon-chain packing organization, which appeared above the orthorhombic hydrocarbon-chain packing organization, transformed to the liquid phase at about 90 °C in HSC. In psoriatic SC (PSC), hexagonal hydrocarbon-chain packing organization disappeared at about 65 °C with elevated temperatures. No high-temperature hexagonal hydrocarbon-chain packing organization were observed in PSC during heating process. Disorder of the hydrocarbon-chain packing of SC lipids was observed in PSC via FT-IR. In UPLC-TOFMS, free fatty acid (FFA) and ceramide (CER) compositions differed between patients with PSC and HSC. Specifically, the levels of ultra-long chain fatty acids containing CER and phytosphingosine-containing CER were decreased, while those of sphingosine and dihydrosphingosine-containing CER and unsaturated FFA were increased in PSC. Furthermore, FFA and CER carbon chain lengths decreased in patients with PSC. These results suggest that the alteration of SC lipid composition and the reduction of carbon chain lengths in PSC lowered the structural transformation temperature, thereby reducing barrier function.


Gas6, a ligand for the receptor protein-tyrosine kinase Tyro-3, is widely expressed in the central nervous system.
Gas6 (growth arrest specific gene-6) is a ligand for members of the Axl subfamily of receptor protein-tyrosine kinases. One of these receptors, Tyro-3, is widely expressed in the central nervous system. We have used biochemical and histological techniques, including in situ hybridization, to determine the expression patterns of Gas6 mRNA and protein during development. Gas6 is widely expressed in the rat central nervous system (CNS) beginning at late embryonic stages and its levels remain high in the adult. Gas6 is detected as a single 85 kDa protein, which is encoded by a single 2.5 kb mRNA species. At embryonic day 14 it is detected in the heart, blood vessels, testes, choroid plexus, and in the ventral spinal cord. In the adult, Gas6 is expressed in the cerebral cortex, (predominantly in layer V), the piriform cortex, and the hippocampus (areas CA1, CA3 and the dentate gyrus). It is also expressed in thalamic and hypothalamic structures, the midbrain, and in a subset of motor and trigeminal nuclei. In the cerebellum, it is expressed in Purkinje neurons and deep cerebellar nuclei. Protein S, a protein related to Gas6, is only detected at low levels in the CNS. The spatial and temporal profiles of Gas6 expression suggest that it could potentially serve as the physiologically relevant ligand for Tyro-3 in the postnatal rat nervous system.


Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film.
The aim of this study was to better understand the underlying drug release characteristics from chitosan-alginate matrix tablets containing different types of drugs. Theophylline, paracetamol, metformin hydrochloride and trimetazidine hydrochloride were used as model drugs exhibiting significantly different solubilities (12, 16, 346 and >1000 mg/ml at 37 °C in water). A novel concept raised was that drugs were released from chitosan-alginate matrix tablets based on the theory of a self-assembled film-controlled release system. The film was only formed on the surface of tablets in gastrointestinal environment and originated from chitosan-alginate polyelectrolyte complex, confirmed by differential scanning calorimetry characterization. The formed film could decrease the rate of polymer swelling to a degree, also greatly limit the erosion of tablets. Drugs were all released through diffusion in the hydrated matrix and polymer relaxation, irrespective of the drug solubility. The effects of polymer level and initial drug loading on release depended on drug properties. Drug release was influenced by the change of pH. In contrast, the impact of ionic strength of the release medium within the physiological range was negligible. Importantly, hydrodynamic conditions showed a key factor determining the superiority of the self-assembled film in controlling drug release compared with conventional matrix tablets. The new insight into chitosan-alginate matrix tablets can help to broaden the application of this type of dosage forms.


Porcine acellular dermal matrix accelerates wound healing through miR-124-3p.1 and miR-139-5p.
Cutaneous wound management is a major health problem and imposes a huge economic burden worldwide. Previous studies have demonstrated that wound healing is a highly coordinated process including epithelialization, angiogenesis, remodeling and scarring. This progression requires self-renewal, preservation and repair properties of stem cells. However, our understanding of the detailed internal regulatory mechanism following injury and the means to accelerate wound healing are limited. Our previous research revealed that porcine acellular dermal matrix (ADM) effectively promotes wound healing and scar formation through epidermal stem cells (ESCs), and this process is relevant to the alteration of internal miRNA levels. In this study, we investigated the regulatory function of porcine ADM treatment on miRNAs in ESCs. We report that the treatment of porcine ADM reduced the levels of miR-124-3p.1 and miR-139-5p in wounds. MiR-124-3p.1 and miR-139-5p inhibited the expression of JAG1 and Notch1, respectively, by directly targeting miRNAs in ESCs. This work demonstrates that porcine ADM induced down-regulation of miR-124-3p.1/139-5p in wounds and up-regulation of JAG1/Notch1 in ESCs, thus enhancing cutaneous wound healing.


Solitary fibrous tumours (SFT) are rare soft tissue tumours with a primarily benign course. Complete surgical resection is the mainstay treatment. In this case report, a 75-year-old man had a massive intrathoracic SFT which was subsequently surgically resected without complications. Although the clinical presentation and CT features of these tumours can mimic lung cancer, the clinical course is significantly more favourable. Diagnostic examination and surgical treatment of intrathoracic SFT should be considered even in patients with increased post-operative risk.


Spatial clustering of fatal, and non-fatal, suicide in new South Wales, Australia: implications for evidence-based prevention.
Rates of suicide appear to be increasing, indicating a critical need for more effective prevention initiatives. To increase the efficacy of future prevention initiatives, we examined the spatial distribution of suicide deaths and suicide attempts in New South Wales (NSW), Australia, to identify where high incidence 'suicide clusters' were occurring. Such clusters represent candidate regions where intervention is critically needed, and likely to have the greatest impact, thus providing an evidence-base for the targeted prioritisation of resources. Analysis is based on official suicide mortality statistics for NSW, provided by the Australian Bureau of Statistics, and hospital separations for non-fatal intentional self-harm, provided through the NSW Health Admitted Patient Data Collection at a Statistical Area 2 (SA2) geography. Geographical Information System (GIS) techniques were applied to detect suicide clusters occurring between 2005 and 2013 (aggregated), for persons aged over 5 years. The final dataset contained 5466 mortality and 86,017 non-fatal intentional self-harm cases. In total, 25 Local Government Areas were identified as primary or secondary likely candidate regions for intervention. Together, these regions contained approximately 200 SA2 level suicide clusters, which represented 46% (n = 39,869) of hospital separations and 43% (n = 2330) of suicide deaths between 2005 and 2013. These clusters primarily converged on the Eastern coastal fringe of NSW. Crude rates of suicide deaths and intentional self-harm differed at the Local Government Areas (LGA) level in NSW. There was a tendency for primary suicide clusters to occur within metropolitan and coastal regions, rather than rural areas. The findings demonstrate the importance of taking geographical variation of suicidal behaviour into account, prior to development and implementation of prevention initiatives, so that such initiatives can target key problem areas where they are likely to have maximal impact.


Antimicrobial and antioxidative potential of free and immobilised cellobiose dehydrogenase isolated from wood degrading fungi.
Cellobiose dehydrogenase (CDH, EC 126.96.36.199) is a glycoprotein having many biotechnological applications. In the present study, CDHs isolated from Phlebia lindtneri (PlCDH), Phanerochaete chrysosporium (PchCDH), Cerrena unicolor (CuCDH), and Pycnoporus sanguineus (PsCDH) were studied the first time for their ability to generate antioxidant and antimicrobial agents. The aim of the research was to evaluate the antioxidant and antimicrobial activity of systems composed of four CDHs and lactose or cellobiose as a reaction substrate. The free radical scavenging effect of free and immobilised enzymes was evaluated using the DPPH method. The lowest values of EC50 (10.04 ± 0.75 μg/ml) was noted for PlCDH/lactose and for PlCDH/cellobiose (12.06 ± 1.35 μg/ml). The EC50value reached 12.6 ± 1.51 μg/ml in the case of PsCDH/lactose and 15.96 ± 1.35 for PsCDH. The CDH preparations were also effectively immobilised in alginate (the immobilisation efficiency expressed as a protein yield ranged from 61.6 to 100 %). The operational stability expressed as a scavenging effect showed the possibility of using the alginate beads 4 times. Both the free and immobilised CDHs as well as the CDH/substrate were tested against Gram-negative Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Gram-positive Staphylococcus aureus ATCC 25923 bacteria. All samples, except PlCDH, were potentially effective in suppression of bacterial growth. The highest percentage of inhibition (100 %) was obtained for S. aureus bacteria using PsCDH and PchCDH with lactose as a substrate, whereas a slightly lesser effect was observed for E. coli and P. aeruginosa bacterial cells, i.e. 64.1 % and 86.5 % (PsCDH) and 94.1 % and 41.4 % (PchCDH), respectively. Furthermore, the concentrations of the reaction products (aldonic acids and hydrogen peroxide) were quantified and the surface morphology of the alginate beads was analysed using SEM visualisation.


GP trainees' values and knowledge regarding global health competencies.
Globalisation is having a significant impact on health through the increasingly interconnected nature of our world, population movement and effects of political and environmental issues. In response, medical educators are urged to review postgraduate training programmes to ensure that doctors are up-to-date with training in contemporary global health issues. Positioned on the frontline of healthcare provision, GPs have an integral role to play in addressing local and global health inequities. However, GP trainees in the UK currently receive little formal education on global health. We sought to investigate GP trainees' understanding and perceived competence in relation to global health issues and cross-cultural practice and their views regarding whether it is indeed time for GP postgraduate training to 'go global'. We invited trainees across Health Education England: Wessex (N = 476) to complete an anonymous online questionnaire. The majority of respondents either 'agreed' or 'strongly agreed' that 'it is important for doctors training to be GPs in the UK to have education on global health' (89%). Similarly, the majority either 'agreed' or 'strongly agreed' that 'it is important for doctors training to be GPs in the UK to develop intercultural competence' (93%). In contrast to the high degree of importance that GP trainees placed on establishing proficiency in these domains, approximately half (45-54%) reported their current level of competence as only being 'average'. Our findings indicate a mismatch and unmet need for further training in the postgraduate setting, with strong GP trainee support for a shift in curriculum design and delivery, towards more globally competent general practice.


Sensitive detection of SARS coronavirus RNA by a novel asymmetric multiplex nested RT-PCR amplification coupled with oligonucleotide microarray hybridization.
We have developed a sensitive method for the detection of specific genes simultaneously. First, DNA was amplified by a novel asymmetric multiplex PCR with universal primer(s). Second, the 6-carboxytetramethylrhodamine (TAMRA)-labeled PCR products were hybridized specifically with oligonucleotide microarrays. Finally, matched duplexes were detected by using a laser-induced fluorescence scanner. The usefulness of this method was illustrated by analyzing severe acute respiratory syndrome (SARS) coronavirus RNA. The detection limit was 10(0) copies/microL. The results of the asymmetric multiplex nested reverse transcription-PCR were in agreement with the results of the microarray hybridization; no hybridization signal was lost as happened with applicons from symmetric amplifications. This reliable method can be used to the identification of other microorganisms, screening of genetic diseases, and other applications.


Timescales of gut microbiome dynamics.
Vast communities of microorganisms inhabit the gastrointestinal tracts of humans and other animals. Understanding their initial development, fluctuations in composition, stability over long times, and responses to transient perturbations - in other words their dynamics - is important both for gaining basic insights into these ecosystems and for rationally manipulating them for therapeutic ends. Gut microbiome dynamics, however, remain poorly understood. We review here studies of gut microbiome dynamics in the presence and absence of external perturbations, noting especially the long timescales associated with overall stability and the short timescales associated with various underlying biological processes. Integrating these disparate timescales, we suggest, is an important goal for future work and is necessary for developing a predictive understanding of microbiome dynamics.


Different responses of rodent mast cells to lysophosphatidylserine.
The lysophosphatidylserine-induced activation of mast cells has been studied in preparations obtained from different rodents. In mouse and gerbil peritoneal mast cells lysophosphatidylserine behaves as an agonist, inducing noncytotoxic histamine release at 0.2-8 microM. In rat peritoneal and pleural mast cells lysophosphatidylserine is ineffective, but the histamine-releasing activity becomes manifest upon the addition of suboptimal concentrations of other mast cell activators. The common structure-activity relationship shows the link between these effects of lysophosphatidylserine but the calcium requirement indicates differences in the mechanism of action. Histamine release in mouse mast cells is independent of external calcium. Thus, lysophosphatidylserine induces mobilization of endogenous calcium stores in these cells. By contrast, histamine release in gerbil and rat mast cells is dependent on the addition of external calcium indicating that the phospholipid promotes calcium influx. While in gerbil mast cells calcium influx is promoted by lysophosphatidylserine alone, in rat it requires the combined action of the phospholipid and other mast cell agonists. Differently from lysophosphatidylserine, compound 48/80 elicits histamine release in rat and gerbil mast cells. Mouse mast cells are unaffected. Thus, gerbil mast cells are the only preparation in which the action of these two agonists can be observed simultaneously.


A ROTEM method using APTT reagent and tissue factor as the clotting activators may better define bleeding heterogeneity in moderate or severe haemophilia A (part I: Study in plasma samples).
Bleeding heterogeneity observed in haemophilia A (HA) may attribute to that the available monitoring methods cannot appropriately reflect the coagulation profile. The present study aimed to develop a global approach by changing the clotting initiation way in rotational thromboelastometry (ROTEM) assay. ROTEM was run in Factor VIII (FVIII)-immune-depleted plasma to which different concentrations of recombinant VIII (rFVIII) had been added, and also in 31 patients with HA. The clotting activators were APTT reagent (1.2 × 10-3 of the dose used in the original APTT method) and recombinant tissue factor (0.02 pmol/L). In FVIII-immune-depleted plasma spiked with rFVIII, maximum velocity of coagulation reliably mirrored the rFVIII levels. This dose-response disappeared after the samples were pre-incubated with an antibody against TFPI, protein S, activated prothrombin complex concentrate or rFVIIa known to favour the extrinsic activation. In the HA patients with FVIII 0-0.21 IU/mL, APTT and ROTEM outcomes varied in significant correlations to FVIII activity; however, this correlation became non-significant when only samples with FVIII 0-0.05 IU/mL were included. Conclusions: The decreased coagulation in HA mostly result from deficiency/absence of FVIII; other pro-/anti-thrombotic proteins are also influential. The multiple effects may cause a mismatch between bleeding phenotype and FVIII concentrations. The ROTEM assay with the clotting activators i.e., tiny doses of APTT reagent and TF are more effective than the original APTT method as regards the assay sensitivity to influence by VIII activity and also to that by other pro-/anti-thrombotic proteins, showing the whole coagulation picture behind the phenotypic heterogeneity in HA.


Effects of energy deficit, dietary protein, and feeding on intracellular regulators of skeletal muscle proteolysis.
This study was undertaken to characterize the ubiquitin proteasome system (UPS) response to varied dietary protein intake, energy deficit (ED), and consumption of a mixed meal. A randomized, controlled trial of 39 adults consuming protein at 0.8 (recommended dietary allowance [RDA]), 1.6 (2×-RDA), or 2.4 (3×-RDA) g · kg(-1) · d(-1) for 31 d. A 10-d weight maintenance (WM) period was followed by 21 d of 40% ED. Ubiquitin (Ub)-mediated proteolysis and associated gene expression were assessed in the postabsorptive (fasted) and postprandial (fed; 480 kcal, 20 g protein) states after WM and ED by using muscle biopsies, fluorescence-based assays, immunoblot analysis, and real-time qRT-PCR. In the assessment of UPS responses to varied protein intakes, ED, and feeding, the RDA, WM, and fasted measures served as appropriate controls. ED resulted in the up-regulation of UPS-associated gene expression, as mRNA expression of the atrogenes muscle RING finger-1 (MuRF1) and atrogin-1 were 1.2- and 1.3-fold higher (P<0.05) for ED than for WM. However, mixed-meal consumption attenuated UPS-mediated proteolysis, independent of energy status or dietary protein, as the activities of the 26S proteasome subunits β1, β2, and β5 were lower (P<0.05) for fed than for fasted. Muscle protein ubiquitylation was also 45% lower (P<0.05) for fed than for fasted, regardless of dietary protein and energy manipulations. Independent of habitual protein intake and despite increased MuRF1 and atrogin-1 mRNA expression during ED, consuming a protein-containing mixed meal attenuates Ub-mediated proteolysis.


Induction of apoptosis by takrisodokyeum through generation of hydrogen peroxide and activation of caspase-3 in HL-60 cells.
Takrisodokyeum (TRSDY), a Chinese herbal medicine, has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that TRSDY induced apoptosis in HL-60 cells as evidenced by both a characteristic ladder pattern of discontinuous DNA fragments and an increase of annexin V+/PI- stained cell population. Our data demonstrated that TRSDY-induced apoptotic cell death was accompanied by activation of caspase-3 and cleavages of its substrates, poly(ADP-ribose) polymerase (PARP) and RhoGDP dissociation inhibitor (RhoGDI-2; also called D4-GDI) in a time- and concentration-dependent manner. Caspase-3 inhibitor, but not caspase-1 inhibitor, prevented TRSDY-induced apoptosis. Furthermore, treatment with TRSDY increased the production of intracellular hydrogen peroxide and pretreatment of cells with anti-oxidants conferred complete protection against hydrogen peroxide generation and subsequent caspase-3 activation. Taken together, these results suggest that TRSDY induces hydrogen peroxide generation, which, in turn, causes activation of caspase-3, degradation of PARP and D4-GDI, and eventually leads to apoptotic cell death.


Triple Negative Breast Cancer: Expression of Folate Receptor Alpha in Indian population.
Folate Receptor Alpha (FRA) is a membrane protein expressed on the apical surface of epithelial cells. Its expression in increased in certain tumors, where it can serve as a target for therapy. Triple Negative Breast Carcinoma (TNBC) are a heterogeneous group of tumors, with limited therapy options and poor prognosis. We aimed to study the expression of FRA in TNBC. Tissue microarrays were prepared from archived paraffin blocks of 300 TNBC resection specimens. Staining for FRA immunohistochemistry was carried out using the clone 26B3.F2. Clinical and pathologic details of the patients were obtained from the electronic medical records. Chi square test was performed for correlation of clinicopathological features with FRA expression. Kaplan Meir and Cox Regression analysis were carried out to study the Disease Free Survival (DFS) and Overall Survival (OS). FRA showed positivity in 43% (129/300) of TNBCs in our study. In univariate analysis, TNBC expressing FRA had a significantly better OS compared to FRA negative tumors (p - 0.035). Also, FRA positive tumors showed a trend towards longer DFS, though this was not statistically significant. In multivariate analysis however, FRA expression did not emerge as a significant factor. To conclude, TNBCs in our study showed FRA expression and though this did not emerge as an important prognostic factor, it can represent a therapeutic target for future clinical trials.


Bilateral sternoclavicular joint dislocation due to sternal fracture: Is it a dislocation or a separation?
Traumatic bilateral sternoclavicular joint dislocation is very rare injury. In shoulder girdle injuries, anterior dislocation of the sternoclavicular joint accounts for 3 % and posterior sternoclavicular joint dislocation is lesser. Previous reported cases about bilateral sternoclavicular joint dislocation were result from proximal clavicle fracture with intact connection between sternum and ribs. But, the sternoclavicular joint dislocation secondary to fracture and angulation of the sternum with intact relationship between ribs and clavicle has not been reported. Authors experienced patient who has a bilateral anterior sternoclavicular joint dislocation caused by sternum fracture and anterior angulation, but intact relationship between ribs and clavicle. We report this case with satisfactory result.


The association between diabetic retinopathy and skeletal muscle capillary basal lamina thickening corrected for the influence of age and duration of diabetes.
The association between an objective measure of diabetic retinopathy and skeletal muscle capillary basal lamina thickness was examined in a group of 30 male insulin-treated diabetic subjects, mean age (+/- SD) 44.6 +/- 13.2 yr, duration of diabetes 21.2 +/- 11.2 yr, % ideal body weight (% IBW) 106 +/- 11%. In addition, muscle capillary basal lamina width was measured in a group of 18 nondiabeitc men, mean age 40.7 +/- 16.3 yr and % IBW 118 +/- 23%. The muscle capillary width of the diabetic subjects was significantly greater than that of the nondiabetic group (P less than 0.01), but the values of the two overlapped considerably. In the diabetic group, there was a significant association of basal lamina width with age (P less than 0.01) but not with duration of diabetes. The association between extent of retinopathy and muscle capillary basal lamina width was not strong. The findings of the study do not therefore support the use of an estimate of muscle capillary basal lamina thickness as a single representative measure of diabetic microangiopathy.


Supervised recursive segmentation of volumetric CT images for 3D reconstruction of lung and vessel tree.
Three dimensional reconstruction of lung and vessel tree has great significance to 3D observation and quantitative analysis for lung diseases. This paper presents non-sheltered 3D models of lung and vessel tree based on a supervised semi-3D lung tissues segmentation method. A recursive strategy based on geometric active contour is proposed instead of the "coarse-to-fine" framework in existing literature to extract lung tissues from the volumetric CT slices. In this model, the segmentation of the current slice is supervised by the result of the previous one slice due to the slight changes between adjacent slice of lung tissues. Through this mechanism, lung tissues in all the slices are segmented fast and accurately. The serious problems of left and right lungs fusion, caused by partial volume effects, and segmentation of pleural nodules can be settled meanwhile during the semi-3D process. The proposed scheme is evaluated by fifteen scans, from eight healthy participants and seven participants suffering from early-stage lung tumors. The results validate the good performance of the proposed method compared with the "coarse-to-fine" framework. The segmented datasets are utilized to reconstruct the non-sheltered 3D models of lung and vessel tree.


On the aging of organisms and their cells.
An explanation of organismic ageing based on a limited division capacity of dividing cells is difficult to reconcile with much of the available data. The physiology of cells in ageing organisms tends, on the contrary, to suggest that organisms age as a result of degeneration in their non-dividing cell populations. Senescence in these non-mitotic cells resmebles the ageing of the non-dividing fraction of cell cultures clonally senescing, or maintained in long-term quiescence in vitro. As cultures of diploid human fibroblasts senesce there is an accumulation of non-dividing cells. Alterations in these post-mitotic cells can explain the senescent properties of late passage cultures. It is proposed that during the in vitro senescence of fibroblast cultures, cell ageing results from, as opposed to causes, the absence of mitosis. Cell ageing may primarily result from changes in the chromatin induced by the non-mitotic state.


Lactobacillus reuteri improves function of the intestinal barrier in rats with acute liver failure through Nrf-2/HO-1 pathway.
We aimed to explore whether Lactobacillus reuteri could have a positive role in reducing inflammation and bacterial translocation in rats with acute liver failure. Lactobacillus reuteri were gavaged to Sprague-Dawley (SD) rats at a dose of 1 × 109 CFU/mL once a day for 14 d. D-galactosamine was injected intraperitoneally to induce acute liver failure for 24 h on the 15th day. Liver function, liver and ileum histology, intestinal cytokines, intestinal tight junction proteins, lipopolysaccharide binding protein, apoptosis molecules, and nuclear factor erythroid-derived 2 (Nrf-2) / heme oxygenase (HO-1) molecules were assessed. The results showed that L. reuteri alleviated liver injury and intestinal inflammation induced by D-galactosamine. L. reuteri also improved the expression of intestinal tight junction proteins and maintained the integrity of the intestinal barrier by inhibiting apoptosis of intestinal epithelial cells. L reuteri induced an increase in Nrf-2 nuclear translocation and elevated induction of HO-1. L. reuteri treatment significantly enhanced the expression of phosphoinositide 3-kinase/protein kinase B (PI3 K/Akt), protein kinase C (PKC), and their phosphorylated forms but not mitogen-activated protein kinase. The nuclear factor kappa B (NF-κB) pathway was inhibited after L. reuteri treatment. Interleukin (IL)-17A produced by Th17 cells and γδT17 cells may not contribute to an improved function of the intestinal barrier in L. reuteri-treated SD rats. Overall, our study indicated that L. reuteri-induced expression of intestinal tight junction proteins is mediated by the PI3 K/Akt-Nrf-2/HO-1-NF-κB and PKC-Nrf-2/HO-1-NF-κB pathways, which leads to inhibition of the apoptosis of intestinal epithelial cells, thus maintaining the integrity of the damaged intestinal barrier.


Circadian rhythm of core body temperature in two laboratory mouse lines.
The circadian rhythm of core body temperature (Tb) was examined in two mouse lines bidirectionally selected for nest-building behavior (small (SNB) and big nest-builders (BNB)). This selection also resulted in more robust circadian organization of wheel-running activity in the SNB compared to the BNB mice. Tb was measured by an e-mitter implanted in the abdominal cavity. The circadian Tb rhythm of the SNB was more robust compared to the BNB regardless of whether the animals had access to a running wheel or not and regardless of the lighting conditions, i.e., 12 h:12 h light:dark (LD) cycle or constant dark (DD). Wheel-running activity rhythms of SNB were more robust in LD and DD compared to BNB. The amplitude of the circadian Tb rhythm increased significantly in response to wheel access in both mouse lines, but was not significantly different between the BNB and SNB. However, BNB tended to have lower amplitudes of circadian Tb rhythm in the absence of running wheels and a larger increase in the amplitude upon access to a running wheel compared to SNB. No differences were found in LD and DD between the lines in mean Tb and wheel-running activity levels. In addition, no differences between the two mouse lines were found in the free-running period of the Tb or wheel-running activity rhythms in DD. Overall, our findings reveal a more robust circadian phenotype of the SNB compared to the BNB.


Identification of the driving factors of microplastic load and morphology in estuaries for improving monitoring and management strategies: A global meta-analysis.
Estuaries are one of the primary pathways for transferring microplastics (MPs) from the land to the ocean. A comprehensive understanding of the load, morphological characteristics, driving factors, and potential risks of MPs in estuaries is imperative to inform reliable management in this critical transboundary area. Extracted from 135 publications, a global meta-analysis comprising 1477 observations and 124 estuaries was conducted. MP abundance in estuaries was tremendously variable, reaching a mean of 21,342.43 ± 122,557.53 items/m3 in water and 1312.79 ± 6295.73 items/kg in sediment. Fibers and fragments take up a majority proportion in estuaries. Polyester, polypropylene, and polyethylene are the most detected MP types. Around 68.73% and 85.51% of MPs detected in water and sediment are smaller than 1 μm. The redundancy analysis revealed that the explanatory factors influencing the morphological characteristics of MPs differed between water and sediment. Regression analysis shows that MP abundance in water is significantly inversely correlated with mesh/filter size, per capita plastic waste, and the Human Development Index, whereas it is significantly positively correlated with population density and share of global mismanaged plastic waste. MP abundance in sediment significantly positively correlated with aridity index and probability of plastic entering the ocean, while significantly negatively correlated with mesh/filter size. Analysis based on Geodector identified that the extraction method, density of flotation fluid, and sampling depth are the top three explanatory factors for MP abundance in water, while the share of global mismanaged plastic waste, the probability of plastic being emitted into the ocean, and population density are the top three explanatory factors for MP abundance in sediment. In the studied estuaries, 46.75% of the water and 2.74% of the sediment are categorized into extremely high levels of pollution, while 73.08% of the water and 43.48% of the sediment belong to class V of the potential ecological index.


A novel double-surface coil approach to phosphorus-31 spectroscopy: a study of hemispheric brain injury in the rat.
An arrangement of two surface coils was devised to allow phosphorus-31 (31P) NMR spectroscopy of a localized hemispheric brain injury model in the rat. Two elliptical (8 X 12 mm) surface coils are placed parallel to each other (3 mm apart) over each side of the rat head. Spectra are collected from either the normal or the injured side of the head using the appropriate surface coil. A passive detuning method was used to eliminate unwanted coil-coil interactions. 31P imaging results with the two coils on phantoms show excellent isolation (6% signal overlap) between the two coils. The two-coil setup was then used to follow a time course of injury from the hemispheric injury model.


Evaluating the ability of artificial neural network and PCA-M5P models in predicting leachate COD load in landfills.
Waste burial in uncontrolled landfills can cause serious environmental damages and unpleasant consequences. Leachates produced in landfills have the potential to contaminate soil and groundwater resources. Leachate management is one of the major issues with respect to landfills environmental impacts. Improper design of landfills can lead to leachate spread in the environment, and hence, engineered landfills are required to have leachate monitoring programs. The high cost of such programs may be greatly reduced and cost efficiency of the program may be optimized if one can predict leachate contamination level and foresee management and treatment strategies. The aim of this study is to develop two expert systems consisting of Artificial Neural Network (ANN) and Principal Component Analysis-M5P (PCA-M5P) models to predict Chemical Oxygen Demand (COD) load in leachates produced in lab-scale landfills. Measured data from three landfill lysimeters, including rainfall depth, number of days after waste deposition, thickness of top and bottom Compacted Clay Liners (CCLs), and thickness of top cover over the lysimeter, were utilized to develop, train, validate, and test the expert systems and predict the leachate COD load. Statistical analysis of the prediction results showed that both models possess good prediction ability with a slight superiority for ANN over PCA-M5P. Based on test datasets, the mean absolute percentage error for ANN and PCA-M5P models were 4% and 12%, respectively, and the correlation coefficient for both models was greater than 0.98. Developed models may be used as a rough estimate for leachate COD load prediction in primary landfill designs, where the effect of a top and/or bottom liner is disputed.