Threshold values of visceral fat and waist girth in Japanese obese children.
In order to define the diagnostic criteria for visceral adipose tissue (VAT) accumulation and abdominal obesity in Japanese youths, a cross-sectional, multicenter study was conducted. Subjects were 194 boys and 96 girls ranging in age from 6 to 15 years. Obese youths were classified according to the occurrence of abnormal values in serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion was calculated, using the analysis of receiver operating characteristic (ROC) curve. The areas of total abdominal adipose tissue (AT), VAT and subcutaneous adipose tissue (SAT) were estimated by single slice computed tomography at the level of umbilicus. VAT area was greater in boys than it was in girls. The critical values for VAT area and waist circumference in all subjects were 54.8 cm2 and 83.5 cm, respectively. The values for the area under the ROC curves were VAT area > total AT area > waist circumference > SAT area > percentage overweight > percentage body fat. The sensitivity and specificity for VAT area were 90.5 and 79.5%, respectively. Those for waist circumference were high enough (> 70%) for clinical use. In the linear regression analysis assigning VAT area as an independent variable and waist circumference as a dependent variable, the expected value for the waist circumference was 82 cm. In Japanese obese youths ranging in age from 6 to 15 years, the diagnostic criteria for the waist circumference was 82 cm, and that for VAT area was 55 cm2.


CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX3CL1 (fractalkine) in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX3CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX3CL1 and CX3CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis (EAE). The expression of CX3CL1 and its receptor CX3CR1 was studied with in situ hybridization histochemical detection of their mRNA with radio labeled cRNA probes in combination with immunohistochemical staining of phenotypic cell markers. Both healthy rat brains and brains from rats with MOG EAE were analyzed. In defined lesional stages of MOG EAE, the number of CX3CR1 mRNA-expressing cells and the intensity of the in situ hybridization signal were determined by image analysis. Data were statistically evaluated by ANOVA, followed by Tukey\primes multiple comparison test. Expression of CX3CL1 mRNA was present within neuronal-like cells located throughout the neuraxis of the healthy rat. Expression of CX3CL1 remained unaltered in the CNS of rats with MOG-induced EAE, with the exception of an induced expression in astrocytes within inflammatory lesions. Notably, the brain vasculature of healthy and encephalitic animals did not exhibit signs of CX3CL1 mRNA expression. The receptor, CX3CR1, was expressed by microglial cells in all regions of the healthy brain. Induction of MOG-induced EAE was associated with a distinct accumulation of CX3CR1 mRNA expressing cells within the inflammatory brain lesions, the great majority of which stained positive for markers of the microglia-macrophage lineage. Analysis in time-staged brain lesions revealed elevated levels of CX3CR1 mRNA in microglia in the periplaque zone, as well as a dramatically enhanced accumulation of CX3CR1 expressing cells within the early-active, late-active and inactive, demyelinated lesions. Our data demonstrate constitutive and regulated expression of the chemokine CX3CL1 and its receptor CX3CR1 by neurons/astrocytes and microglia, respectively, within the normal and inflamed rat brain. Our findings propose a mechanism by which neurons and reactive astrocytes may control migration and function of the surrounding microglia. In addition, the accumulation of CX3CR1 expressing cells other than microglia within the inflammatory brain lesions indicate a possible role for CX3CL1 in controlling invasion of peripheral leucocytes to the brain.


Development of novel nanoantibiotics using an outer membrane vesicle-based drug efflux mechanism.
Conventionally used antibiotics are present in low concentrations at the infection site and require multiple administrations to sustain a continuous bactericidal effect, which not only increases their systemic toxicity but also results in bacterial drug resistance. In this study, we first identified an interesting drug resistance mechanism mediated by bacterial outer membrane vesicles (OMVs) and then designed novel antibiotic-loaded OMVs using this mechanism. We show that these antibiotic-loaded OMVs can effectively enter and kill pathogenic bacteria in vitro. In a mouse model of intestinal bacterial infection, one low-dose oral administration of antibiotic-loaded OMVs showed that the drug was retained in the intestine for 36 h, and no systemic spread was detected 12 h after drug administration. The antibiotic-loaded OMVs significantly reduced the bacterial load in the small intestine and feces of infected mice. Safety experiments confirmed that the antibiotic-loaded OMVs had excellent biocompatibility. This study extends the application range of OMVs and provides new ideas for the development of antibacterial drugs.


Mycotoxins in soil and environment.
Mycotoxins are secondary metabolites produced by specific fungi that have harmful effects on animals and humans. Worldwide more than 300 different mycotoxins are already known, frequently with concentrations in harvest products exceeding acceptable limits. Nevertheless, although these compounds have extensively been studied in food and feed, only little is known about their occurrence and fate in soil and agro-environmental matrices, such as manure, sewage sludge, drainage water and sediments. Therefore, the aim of this review was to (i) resume available methods for quantifying mycotoxins in soil, (ii) describe the occurrence and quantities of mycotoxins in soil and related agro-environmental matrices, and (iii) discuss the environmental fate of these target compounds with specific focus on their leaching potential into groundwater. The safest and most reliable method for mycotoxin quantification relies on mass spectrometry, while the extraction method and solvent composition differ depending on the compound under investigation. Mycotoxin levels detected in soils to date were in the μg range, reaching maximum amounts of 72.1 μg kg-1 for zearalenone, 32.1 μg kg-1 for deoxynivalenol, 23.7 μg kg-1 for ochratoxin A, 6.7 μg kg-1 for nivalenol, and 5.5 μg kg-1 for aflatoxin. Different compartments in the agroecosystem (cereals, corn, rice, water, manure, sewage sludge) each contained at least one mycotoxin. Mycotoxin retention in soils is controlled by texture, with significant adsorption of the compounds to clays but leaching potentials in sandy soils. We did not find any reports detecting mycotoxins in sediments, although there are increasing reports of mycotoxins in freshwater samples. Overall, it appears that soils and sediments are still underrepresented in research on potential environmental contamination with mycotoxins.


Regulatory effects of human IgE-binding factors in the IgE synthesis by human and rat lymphocytes.
We have previously established human T cell hybridomas which produce IgE-binding factors. Incubation of one of the T cell hybridomas, 166A2, with human IgE dimer in the presence of 1 microgram/ml bradykinin resulted in the formation of IgE-binding factors having affinity for lentil lectin. The factors selectively enhanced both IgE-forming cell responses of rat mesenteric lymph node (MLN) cells and spontaneous IgE synthesis by human peripheral blood B cells of atopic patients, without affecting the IgG response. The same factors that enhanced IgE synthesis of B cells from atopic patients also enhanced IgE synthesis induced under bystander conditions by activated alloreactive T cells. Fractionation of the affinity-purified IgE-binding factors by gel filtration revealed three molecular mass species, i.e., 60 kDa, 30 kDa and 15 kDa. The 60-kDa and 15-kDa IgE-binding factors selectively enhanced both the spontaneous IgE synthesis by B cells of atopic patients and IgE response of rat MLN cells. In contrast, the 30-kDa IgE-binding factors had only marginal enhancing effects on the IgE synthesis by both human B cells and rat MLN cells. When the 166A2 hybridoma cells were incubated with IgE dimer in the presence of glycosylation-inhibiting factor (GIF), essentially all IgE-binding factors formed by the cells had affinity for peanut agglutinin (PNA) but for neither lentil lectin nor concanavalin A. All of the 60-kDa, 30-kDa and 15-kDa species, having affinity for PNA, selectively suppressed the potentiating factor-enhanced IgE response of rat MLN cells. The factors also suppressed the IgE synthesis of human B cells from atopic patients when the synthesis was enhanced by IgE-potentiating factor. The results indicate that human IgE-binding factors regulate IgE synthesis by both human and rat lymphocytes.


The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells.
The G protein coupling of human 5-hydroxytryptamine5A (h5-ht5A) receptors was investigated in stably transfected human embryonic kidney (HEK) 293 cells, using radioligand and guanosine-5'[gamma-35S]thiotriphosphate binding to membranes and cyclic adenosine monophosphate measurements in cells. 5-Carboxamido[3H]tryptamine bound to high- and low-affinity sites on h5-ht5A-HEK 293 cell membranes. Guanylyl-imidodiphosphate addition and pertussis toxin pre-treatment abolished high-affinity binding, indicating coupling to G proteins of the Gi/Go family. [N-methyl-3H]Lysergic acid diethylamide bound to a single site; guanylyl-imidodiphosphate and pertussis toxin did not alter lysergic acid diethylamide affinity. 5-Hydroxytryptamine stimulated guanosine-5'[gamma-35S]thiotriphosphate binding to 130% over basal and this effect was completely abolished by pertussis toxin. Various 5-hydroxytryptamine receptor ligands were tested for inhibition of 5-carboxamido[3H]tryptamine binding and in guanosine-5'[gamma-35S]thiotriphosphate binding assays. 5-Hydroxytryptamine consistently inhibited forskolin-induced cyclic adenosine monophosphate formation by 25% in h5-ht5A-HEK 293 cells; no effect was detected on basal cyclic adenosine monophosphate levels, on intracellular Ca2+ concentration or arachidonic acid release. Our studies demonstrate functional coupling of the h5-ht5A receptor to pertussis toxin-sensitive G proteins and to inhibition of adenylate cyclase activity.


Relations between fruit chemical components of biquinho pepper cultivars in different crop seasons.
The species Capsicum chinense, variety biquinho, has been gaining space in cooking, but little is known about its cultivars, mainly related to the chemical composition of fruits. The objective of this study was to characterize the nutritional composition of two biquinho pepper cultivars in different growing seasons and to define the relationships between the variables and their direct and indirect effects. An experiment was conducted in a randomized block design with two cultivars of biquinho pepper, two growing seasons. The variables were plastochron (PLAS), fruit mass (MASS), pH, total soluble solids (Brix), acidity, total phenolic compounds (PHE), carotenoids (CAR), antioxidant potential (ANT), capsaicin (CAP), and dihydrocapsaicin (DIH). The cultivar BRS Moema showed higher levels for chemical compounds, while the cultivar Airetama was the most productive. Principal component analysis (PCA) was performed to determine relationships among variables, and path analysis was used to determine direct and indirect effects between variables. The chemical composition of biquinho pepper is modified according to cultivar and growing season. Important relationships between pH and CAR, ANT, PHE, CAP, and pH. CAR and PHE have an indirect effect and the MASS and PLAS have a direct effect on the ANT.


Neuro-Oncology Patients as Human Research Subjects: Ethical Considerations for Cognitive and Behavioral Testing for Research Purposes.
Language, cognition, and behavioral testing have become a fundamental component of standard clinical care for brain cancer patients. Many existing publications have identified and addressed potential ethical issues that are present in the biomedical setting mostly centering around the enrollment of vulnerable populations for therapeutic clinical trials. Well-established guides and publications have served as useful tools for clinicians; however, little has been published for researchers who share the same stage but administer tests and collect valuable data solely for non-therapeutic investigational purposes derived from voluntary patient participation. Obtaining informed consent and administering language, cognition, and behavioral tasks for the sole purpose of research involving cancer patients that exhibit motor speech difficulties and cognitive impairments has its own hardships. Researchers may encounter patients who experience emotional responses during tasks that challenge their existing impairments. Patients may have difficulty differentiating between clinical testing and research testing due to similarity of task design and their physician's dual role as a principal investigator in the study. It is important for researchers to practice the proposed methods emphasized in this article to maintain the overall well-being of patients while simultaneously fulfilling the purpose of the study in a research setting.


Ocular tolerance of preservatives and alternatives.
Eye drops are multiple dosage forms protected against microbial contamination by means of preservatives. However, the ocular tolerance of these chemicals can vary and this may result in adverse toxic or allergic reactions. This overview presents the pharmacopoeial requirements for the preservation of eye drops, the factors affecting ocular tolerance as well as the adverse external ocular effects induced by preservatives. The alternatives to the use of preservatives are also discussed, including the recent progress in eye drops packaging.


Human amygdala activations during nasal chemoreception.
This review serves as a comprehensive discussion of chemosensory stimulation of the amygdala in healthy humans. Following an introduction of the neuroanatomy of chemosensory processing in primary and secondary olfactory structures, functional resonance magnetic imaging and positron imaging tomography studies are systematically categorized based on valence of stimuli, stimulus concentration, and paradigm-dependent amygdala activation. The amygdala shows patterns of lateralization due to stimulus valence. Main findings include pleasant odors being associated with bilateral or left amygdala activation, and unpleasant odors being associated with activation of the right amygdala, suggesting a crucial role of the right amygdala in evolutionary preservation. Potentially threatening social stimuli, however, might be processed apart from the olfactory system and tend to activate the left amygdala. Amygdala response to chemosensory stimuli correlated with simultaneous activation in the orbitofrontal cortex (OFC), piriform cortex (PC), and insula, suggesting a close-knit network of these areas during stimulus processing.


A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease.
The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro.


Approach to the diagnosis and treatment of nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It describes several clinicopathologic entities from simple hepatic steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. This article describes the epidemiology, clinical features, natural history, and pathogenesis of NAFLD.


A Combined Panel of Salivary Biomarkers in de novo Parkinson's Disease.
To investigate molecular biomarkers of a-synuclein and tau aggregation, autophagy, and inflammation in the saliva of de novo Parkinson's disease (PD) patients in comparison to healthy subjects (HS), and to correlate molecular data with clinical features of PD patients, in order to establish whether abnormalities of these parameters are associated with specific clusters of de novo PD patients, and their potential diagnostic power in differentiating PD patients from HS. We measured total and oligomeric a-synuclein, total-tau and phosphorylated-tau, microtubule-associated protein light chain 3 beta (MAP-LC3beta), and tumor necrosis factor alpha (TNFalpha) in the saliva of 80 de novo PD patients and 62 HS, using quantitative enzyme-linked immunosorbent Assay analysis. Oligomeric a-synuclein, total-tau, MAP-LC3beta, and TNFalpha levels resulted significantly higher in patients with respect to HS, while no significant differences were detected for total a-synuclein or phosphorylated-tau. Phosphorylated-tau directly correlated with MAP-LC3beta, whereas it inversely correlated with TNFalpha in PD patients. An inverse correlation was detected between MAP-LC3beta and non-motor symptoms severity. Principal Component Analysis showed that molecular and clinical parameters were independent of each other in de novo PD patients. Receiver operating characteristic curve analysis reported an accurate diagnostic performance of oligomeric a-synuclein and MAP-LC3beta. The diagnostic accuracy of total a-synuclein increased when it was combined with other salivary biomarkers targeting different molecular pathways. Our study proposes a novel biomarker panel using saliva, a non-invasive biofluid, in de novo PD patients, with implications in understanding the molecular pathways involved in PD pathogenesis and the relevance of different molecular pathways in determining clinical PD subtypes. ANN NEUROL 2023;93:446-459.


DNA microarray-based genotyping of Chlamydophila psittaci strains from culture and clinical samples.
The avian and human pathogen Chlamydophila (C.) psittaci represents a genetically heterogeneous species. To facilitate epidemiological surveys, more rapid yet highly specific molecular tests are needed. Currently used typing methods, i.e. serotyping and PCR-RFLP, have only limited sensitivity and are incapable of covering the wide spectrum of naturally occurring types of C. psittaci strains. In the present study, a new DNA microarray assay based on the ArrayTube (AT) technology was used to genotype C. psittaci in 98 isolates and 23 clinical tissue samples. The present array carries 35 oligonucleotide probes derived from variable domains 2 and 4 of the ompA gene. The assay proved highly sensitive, allowing correct genotyping of DNA from 2 inclusion-forming units. The results of DNA microarray genotyping of cultured strains proved highly concordant with the data from PCR-RFLP typing and serotyping. Sequencing of the ompA gene served as the reference test to verify the accuracy of AT genotyping results. In 15 instances (15.3%), strains were successfully typed by the AT assay, while serotyping and/or PCR-RFLP genotyping failed to produce unambiguous results. Eleven of these samples were ompA sequenced to confirm the AT findings. In addition to the currently accepted nine ompA genotypes, the microarray test was shown to recognise new provisional genotypes, such as Mat116 and YP84. In conclusion, the new AT assay proved to be suitable for rapid, sensitive and reproducible genotyping of C. psittaci strains and can be recommended for routine diagnosis.


Changes in the rectal mucosa induced by hypertonic enemas.
The aspect of the rectal mucosa after administration of hypertonic enemas is occasionally confused with the macroscopic appearance of quiescent ulcerative colitis. Criteria for a diagnosis of enema reaction were derived from a retrospective series and tested prospectively on 11 healthy volunteers. Photographs and biopsies were obtained before and after administration of a sodium phosphate hypertonic enema. Three observers evaluated blindly the "before" and "after" macroscopic and microscopic pictures, graded the features, and made an overall diagnosis. In random studies, two observers mistakenly classified a macroscopic picture, but all correct histologic diagnoses of "before" and "after" biopsies. In decreasing order of discriminating power, the following features of an enema reaction were found to be useful: separation and mucous depletion of the glands (no observer variation), increase in mucosal fragility in 91 per cent of cases (82--100 per cent), edema of the lamina propria in 88 per cent (73--100 per cent), straightening of the basal membrane in 82 per cent (73--91 per cent) and an increase in extruded mucus in 70 per cent (18--100 per cent). In 39 per cent of cases (36--45 per cent), erythrocytes appeared focally in the lamina propria. The effects of hypertonic enemas can be recognized on biopsy.


Heterologous expression and biochemical characterization of novel pyranose 2-oxidases from the ascomycetes Aspergillus nidulans and Aspergillus oryzae.
A gene encoding a pyranose 2-oxidase (POx; pyranose/oxygen 2-oxidoreductase; glucose 2-oxidase; EC 22.214.171.124) was identified in the genome of the ascomycete Aspergillus nidulans. Attempts to isolate POx directly from A. nidulans cultures or to homologously overexpress the native POx (under control of the constitutive gpdA promoter) in A. nidulans were unsuccessful. cDNA encoding POx was synthesized from mRNA and expressed in Escherichia coli, and the enzyme was subsequently purified and characterized. A putative pyranose 2-oxidase-encoding gene was also identified in the genome of Aspergillus oryzae. The coding sequence was synthetically produced and was also expressed in E. coli. Both purified enzymes were shown to be flavoproteins consisting of subunits of 65 kDa. The A. nidulans enzyme was biochemically similar to POx reported in literature. From all substrates, the highest catalytic efficiency was found with D-glucose. In addition, the enzyme catalyzes the two-electron reduction of 1,4-benzoquinone, several substituted benzoquinones and 2,6-dichloroindophenol. As judged by the catalytic efficiencies (k (cat)/k(m)), some of these quinone electron acceptors are better substrates for pyranose oxidase than oxygen. The enzyme from A. oryzae was physically similar but showed lower kinetic constants compared to the enzyme from A. nidulans. Distinct differences in the stability of the two enzymes may be attributed to a deletion and an insertion in the sequence, respectively.


A cohort study of mammography-guided vacuum-assisted breast biopsy in patients with compressed thin breasts (≦ 3 cm).
In the women with compressed thin thickness (≦ 3 cm), mammographic guiding vacuum-assist breast biopsy (MG-VABB) is a technical challenge. We herein report their performance of MG-VABB on suspicious microcalcification by modern mammography. We retrospectively reviewed the consecutive MG-VABB in our hospital from February 2019 to January 2021. All the patients received biopsy because of suspicious microcalcifications discovered by mammography and had at least one-year post-biopsy follow-up. We reviewed 745 consecutive patients revealing 195 with compressed thin breasts ≦ 3 cm (mean age: 50.12 ± 7.0; breast thickness: 24.99 mm range 11.6-30 mm). Of the 191 patients received biopsy, the microcalcification retrieval rate was 97.9%. Using the half-open notch biopsy or horizontal needle approach, the biopsies were technically achieved in 30.4% and 9.4% of patients respectively. Regarding to the gold standard of surgicohistology, the cancer sensitivities was 88.46% and the atypia upgrade rate was 16.67%. There was no statistical difference of the procedure time between stereotactic guided and tomosynthesis guided. The modern MG-VABB has technically improve the performance of biopsy to the patients with compressed thin breasts (≦ 3 cm), revealing approximate results to those breasts > 3 cm. The diagnosis helps the management of suspicious microcalcifications discovered by mammography.


Delivery of cell membrane impermeable peptides into living cells by using head-to-tail cyclized mitochondria-penetrating peptides.
A series of cyclic Arg-rich mitochondria-penetrating peptides were prepared with variation in the macrocycle size and the chirality of Arg residues. A cyclic heptapeptide was demonstrated to be an efficient mitochondria-specific delivery vector for delivering membrane impermeable peptides.


Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface.
The influenza A virus M2 protein is expressed abundantly at the cell surface, and in addition to the hemagglutinin (HA) and neuraminidase (NA), is a third virus-specific membrane protein. M2 has an internal hydrophobic membrane anchorage domain and associates with the same cellular membrane fractions as HA and NA. Trypsin treatment of infected cells and immunoprecipitation with site-specific antisera indicate that a minimum of 18 NH2-terminal amino acids of M2 are exposed at the cell surface. Ten NH2-terminal residues are conserved in all strains of influenza A virus for which sequences are available. Antibodies can recognize M2 on the cell surface and therefore it may be an infected-cell surface antigen. We discuss properties of M2 that match it to the elusive major target molecule on influenza A virus-infected cells for cross-reactive cytotoxic T cells.


Seizure susceptibility to electroconvulsions or pentylenetetrazol after complete cerebral ischemia in rats due to cardiac arrest.
Experimental data provide evidence on the induction of a susceptibility to audiogenic seizures in rats surviving cardiac arrest and subsequent global brain ischemia. The aim of this study was to find out whether cardiac arrest in rats could affect seizure susceptibility in the long-term period of one and two months, following this event. Seizure susceptibility was evaluated against electroconvulsions and pentylenetetrazol-induced seizures. Experiments were conducted on 34 rats surviving cardiac arrest and 34 sham-operated animals which also had surgery but their hearts were not stopped. The threshold for electroconvulsions and pentylenetetrazol was calculated in 3 groups of 5-6 rats. The endpoint for electroconvulsions was the tonic hindlimb extension and for pentylenetetrazol-generalized clonic seizure. The results indicate that cardiac arrest did not modify the threshold for electroconvulsions either one or two months, following the surgery. On the other hand, a significant reduction in the seizure threshold for pentylenetetrazol was noted one month after cardiac arrest. The median convulsive dose of pentylenetetrazol was decreased from 52.47 mg/kg (sham-operated rats) to 34.03 mg/kg of the convulsant for the induction of clonic seizure activity. This effect was not observed at two months after cardiac arrest. It is evident that global brain ischemia is associated with a transient reduction in the convulsive threshold for pentylenetetrazol whilst the threshold for electroconvulsions remains unchanged.


The needs of persons with chronic health conditions to maintain or return to work 30 years after transformation from socialism into capitalism - a preliminary report from the Polish part of the PATHWAYS project.
An increased burden of chronic diseases in the working age population is observed across high income countries. Persons with chronic diseases (PwCDs) are less likely to maintain or return to work due to several constraints they experience. The purpose of the study was to assess the preferences and needs of PwCDs regarding 6 areas of flexibility at the workplace. It was assessed whether there were any personal characteristics associated with higher or lower expectations and needs. This was a part of a large multicenter international project, i.e., the PArticipation To Healthy Workplaces And inclusive Strategies in the Work Sector (PATHWAYS) project, aimed to contribute to the development of innovative approaches to promote professional integration and reintegration of PwCDs into the work sector. In Poland, 59 respondents diagnosed with different chronic diseases were identified through advocacy groups. An on-line survey was conducted to collect information on their needs and expectations. A cluster analysis was performed to reveal some expectation types which differentiated individuals across 6 analyzed domains, along with a multivariable logistic regression to identify some characteristics associated with a special expectation type. Workplace facilitator items were generally scored as needed ("rather conductive" and "very conductive" groups identified). The factors positively associated with higher needs in this domain were education, and a hindering type of the disease. Unrestricted working hours were very conductive or indifferent, and were positively associated with education. Legal solutions were more conductive for older people. Medical support, access to training, and supervisors' knowledge were needed in general, with no associations with the personal characteristics identified. Persons with chronic diseases report several facilitators which are needed for them to maintain or return to work, but they are not satisfied with the existing economy in Poland. These needs should be taken into consideration in the effective policy development. Int J Occup Med Environ Health. 2020;33(4):427-44.


iNOS-mediated secondary inflammatory response differs between rat strains following experimental brain contusion.
Nitric oxide is a key mediator of post-traumatic inflammation in the brain. We examined the expressions of iNOS, nNOS, and eNOS in inbred DA and PVGa rat strains where DA is susceptible to autoimmune neuroinflammation and PVGa-resistant. Parietal contusions using a weight drop model were produced in five rats per genotype. After 24 h, the brains were removed and analyzed using a range of immunohistochemical methods. PVGa presented significantly increased iNOS expression in infiltrating inflammatory cells in the perilesional area compared to DA (p < 0.05). The amount of w3/13-positive infiltrating inflammatory cells did not differ between strains. eNOS and nNOS expression did not differ between strains. iNOS-positive cells coexpressed neuronal (NeuN), macrophage (ED-1), and leucocyte (w3/13) markers. MnSOD was significantly increased in PVGa (p < 0.05). 3-Nitrotyrosine, a measure of peroxynitrite levels, and fluoro-jade stained neuronal degeneration, did not differ between strains. Two inbred rat strains with genetically determined differences in susceptibility to develop autoimmune disease displayed different levels of the inflammatory and anti-inflammatory mediators iNOS and MnSOD, indicating genetic regulation. Interestingly, the increased levels of iNOS did not lead to elevated expression of the neuronal cell-death marker fluoro-jade. The increased iNOS expression was correlated with increased expression of superoxide scavenger MnSOD. Excessive peroxynitrite formation was probably prevented by limitation of available superoxide. Subsequently, the higher expression of potentially deleterious iNOS in PVGa did not result in increased neuronal death.


Usefulness of textural analysis as a tool for noninvasive liver fibrosis staging.
Noninvasive diagnosis of liver fibrosis is a popular topic in the medical literature. Textural analysis on B-mode ultrasound is viewed as a noninvasive tool for fibrosis staging. A liver tissue model is proposed and used to simulate ultrasound images. One hundred and twenty-five patients with chronic hepatitis C were included in this study. Patients were investigated using B-mode ultrasound and liver biopsy (Metavir scoring). A texture analysis tool consisting of 12 algorithms and a logistic regression classifier was implemented and validated. Tissue model parameters were varied and ultrasound images were generated. Texture analysis can discriminate between stages F0 and F4 using actual patient data (accuracy 69.5%) and synthetic images (accuracy 76.6%). A human expert is less sensitive than texture analysis in discriminating subtle changes in ultrasound images. High fibrosis detection accuracies are correlated with larger differences in portal space density (r (2) = 0.5). Accuracies measured when we varied only the fibrosis stage and kept the rest of the tissue parameters constant showed high detection rates only in a narrow parameter interval. The texture analysis system shows limited performance in staging fibrosis and it cannot be used for accurate monitoring of fibrosis evolution over time.


Sternal closure by rigid plate fixation in off-pump coronary artery bypass grafting: a comparative study.
Sternal instability or dehiscence results in serious sternal wound infection. We sought to assess the early outcomes with such a plating system for sternal closure in comparison to the conventional wiring technique in off-pump coronary artery bypass grafting (CABG). Patients who underwent off-pump CABG were enrolled. Thirty-one patients received plate sternal fixation. A total of 64 patients who underwent off-pump CABG by a single surgeon at our hospital from July 2013 to December 2014 were enrolled. Thirty-one patients received plate sternal fixation (Plate group), while 33 received conventional wire closure (Wire group). The early outcomes, including the pain score and analgesic usage count were compared. Dietary intake was also recorded to assess the duration of appetite loss. At discharge, the largest sternal displacement was measured on computed tomography. In the Plate group, the pain scores were significantly lower on post-operative day 5-8 and POD 9-12 from those in the Wire group. The analgesic usage count on POD 9-12 was significantly lower in the Plate group. The duration of appetite loss and hospital stay was significantly shorter in the Plate group. The displacement in both the anterior-posterior and lateral directions was significantly smaller in the Plate group. Sternal closure by rigid plate fixation contributes to a more rapid post-operative recovery through reduced pain.


Effect of hypoxic preconditioning on brain genomic response before and following ischemia in the adult mouse: identification of potential neuroprotective candidates for stroke.
The aim of the present study is to better understand oxygen-sensitive adaptative pathways underlying the hypoxic preconditioning-induced protection of the brain against ischemia. Using oligonucleotide microarrays, we examined the brain genomic response of adult mice following hypoxia preconditioning (8% O2 for 1 or 6 h of hypoxia with reoxygenation 12, 18, 24 h or 72 h) and ischemia (6 h), preceeded (tolerant state) or not, by preconditioning. Real-time PCR was used to validate the results. Most gene expression increases occurred during hypoxia, including those of HIF-1-dependent genes (RTP801, AM, VEGF, p21, GLUT-1), early response genes (IER3) and transcriptional factors (ATF3, C/EBPdelta). A second wave of changes occurred 24 h after reoxygenation (S100A5, TH, Calretinin, PBX3). A third one occurred during ischemia itself, revealing that hypoxic preconditioning modifies the brain genomic response to ischemia. In addition, we show that some identical genes are overexpressed by hypoxia in both neonatal and adult brains (VEGF, EPO, GLUT-1, AM, MTs, C/EBPdelta).


A systematic review of demographic and background factors associated with the development of children's aquatic competence.
Globally, drowning is a leading cause of unintentional injury and death among children. Teaching aquatic competencies (swimming skills and water safety knowledge) to children has been proposed as a prevention strategy. In Australia, however, many children are not meeting standard aquatic competency benchmarks. Exploration of the connection between demographic and background factors and aquatic competencies could provide insight into why differences in acquisition of aquatic knowledge and skills occur. A systematic literature review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed to identify studies that reported on the association between demographic and background factors and aquatic competencies. Nine databases were searched for English language peer-reviewed studies published since 2000. Fourteen studies fulfilled all inclusion criteria. Studies were quasi-experimental or cross-sectional in design, which is considered quality level III-2 or IV, respectively, on the National Health and Medical Research Council Evidence Hierarchy. Study quality was moderate, and risk of bias was high. While aquatic competencies can be taught, this review found that factors including age, gender, geographic residence, medical conditions/disabilities, socioeconomic status, and swimming frequency were significantly associated with the demonstration and/or acquisition of aquatic competencies. This review provides insight into demographic and background factors that are significantly associated with the development of aquatic competence. Whilst further investigation is required to increase the evidence base, these findings may assist in tailoring swimming and water safety programs to accommodate those at-risk of not achieving age-appropriate aquatic competencies.


Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics.
Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer.


Physicochemical characterisation and antimicrobial phototoxicity of an anionic porphyrin in natural deep eutectic solvents.
Natural deep eutectic solvents (NADES) are a newly discovered group of eutectics which has shown promise as a solvent in antimicrobial photodynamic therapy (aPDT). The purpose of this study was to investigate preparations of an anionic porphyrin, meso-tetra-(4-carboxyphenyl)-porphine (TCPP), solubilised in NADES, with regard to their physicochemical and antibacterial properties. The NADES CS (pH∼0), ChX (pH∼4) and MFG (pH∼1) solubilised TCPP with absorption maximum ∼443nm and emission maximum ∼678nm, indicating formation of the TCPP dication. Dilution of TCPP-NADES>1:1 (water) reduced the physical stability of the preparations. The photostability half-lives of TCPP in methanol, MFG, and CS were ∼9h, 6.9h and 3.2h, respectively. Nanomolar concentrations of TCPP solubilised in diluted MFG combined with ⩽27J/cm(2) blue light increased Gram-positive and Gram-negative bacterial phototoxicity, >99.98% and 96% bacterial reduction, respectively, compared to TCPP in PBS/ethanol under equivalent treatment conditions. TCPP solubilised in diluted CS was toxic to bacteria both in the absence (36-72% reduction) and presence of light. TCPP in CS, and in the CS component citric acid, induced a TCPP-concentration dependent increase in Gram-negative phototoxicity relative to controls, which was most pronounced for TCPP-CS. The mechanism behind the increased toxicity is unknown.


Nuclear magnetic resonance in oncology.
The application of nuclear magnetic resonance (NMR) techniques to the diagnosis of cancer was first explored by Damadian, who proposed that benign and malignant tissues could be differentiated on the basis of characteristic differences in spin-lattice and spin-spin relaxation times (T1 and T2) as determined in vitro with NMR spectrometers. Damadian's thesis was very controversial and never gained widespread acceptance. Not all investigators were able to confirm his findings. Moreover, it was improbable that NMR would ever play an important role in the diagnosis of malignancy as long as biopsy was necessary to obtain material for analysis. However, the potential usefulness of NMR in oncology was enhanced considerably by the work of Lauterbur, who showed that NMR signals could be spatially encoded to produce images of the examined object. NMR imaging has made feasible the measurement of the T1 and T2 of lesions without biopsy. Unfortunately, initial efforts at characterizing tissues by in vivo determination of proton relaxation times have yielded disappointing results. Nonetheless, NMR imaging will be a powerful tool for evaluating patients with malignant disease because of the unique anatomic information it can provide without exposure of the patient to ionizing radiation. In vivo NMR spectroscopy of 31P and other sensitive nuclei may add a new dimension to clinical and experimental oncology.


Effects of changes in UV-B radiation levels on biofilm-forming organisms commonly found in cultural heritage surfaces.
Accurate measuring and monitoring methods available since the 1980s have shown that the amount of Ultraviolet B (UV-B) radiation reaching the Earth's surface has increased as a result of degradation of the ozone layer. Since the adoption of the Montreal Protocol in 1987, ozone levels have been recovering successfully. However, in the context of the current climate change, other factors such as changes in cloud patterns and an increased incidence of natural disasters (e.g. fires) may be disrupting this recovery. The present study aimed to investigate the effects of different UV-B radiation levels on biofilms colonising heritage monuments. For this purpose, the effects of current UV-B levels on a biofilm composed of Synechocystis sp. (a cyanobacterium), Bracteacoccus minor (a green alga) and Fusarium sp. (a fungus) were compared at three points along a South-North transect: Portugal, Galicia (NW Spain) and Ireland (from highest to lowest UV-B radiation, respectively). Increased levels of UV-B radiation caused changes in the growth, physiological state and composition of subaerial biofilms, with cyanobacteria being more resistant than green algae to high levels of UV-B. A reduction of fungal growth and extracellular polymer substances (EPS) production was also observed, related to the reduction of biofilm aggregation at high UV-B levels.


Assessment of COVID-19 Website Communication in Languages Other than English by Local Health Departments in the United States.
Managing the information needs of diverse populations through accessible, high-quality, and evidence-based health communication is critical to controlling the COVID-19 pandemic. Access to comprehensive information is especially important for the >25 million limited English proficient (LEP) individuals in the U.S. who prefer to communicate in languages other than English. We assessed the alignment of COVID-19 communication with LEP constituents' needs by examining multilingual content availability on the health department websites of the largest U.S. cities by population. To guide content analysis, we designed a codebook to evaluate six content types, six delivery modes, and three score measures for each website; for each, we measured Holsti's percent of agreement. We then compared the amount of information provided in all combined content types across cities and languages by delivery mode. We thematically analyzed open-ended responses about users' experiences with each city's webpages. We found that COVID-19 information was not presented consistently across languages: many cities provided less information among several delivery modes in other languages compared to English. We found a discrepancy in the amount of information, presentation quality, and ease of navigability of the information among languages and between cities. Users described having negative experiences with most cities' COVID-19 websites in languages other than English. Our findings indicate a gap in the application of the cultural sensitivity approach by local health departments to address issues related to equitable multilingual, multimodal emergency communication, and underscore the need to improve guidelines for communicating public health information as a component of advancing health equity.


Usefulness of intracardiac echocardiography for the diagnosis of cardiovascular implantable electronic device-related endocarditis.
The goal of this study was to compare transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) for the diagnosis of cardiac device-related endocarditis (CDI). The diagnosis of infective endocarditis (IE) was established by using the modified Duke criteria based mainly on echocardiography and blood culture results. No previous studies have compared ICE with TEE for the diagnosis of IE. We prospectively enrolled 162 patients (age 72 ± 11 years; 125 male) who underwent transvenous lead extraction: 152 with CDI and 10 with lead malfunction (control group). Using the modified Duke criteria, we divided the patients with infection into 3 groups: 44 with a "definite" diagnosis of IE (group 1), 52 with a "possible" diagnosis of IE (group 2), and 56 with a "rejected" diagnosis of IE (group 3). TEE and ICE were performed before the procedure. In group 1, ICE identified intracardiac masses (ICM) in all 44 patients; TEE identified ICM in 32 patients (73%). In group 2, 6 patients (11%) had ICE and TEE both positive for ICM, 8 patients (15%) had a negative TEE but a positive ICE, and 38 patients (73%) had ICE and TEE both negative. In group 3, 2 patients (3%) had ICM both at ICE and TEE, 1 patient (2%) had an ICM at ICE and a negative TEE, and 53 patients (95%) had no ICM at ICE and TEE. ICE and TEE were both negative in the control group. ICE represents a useful technique for the diagnosis of ICM, thus providing improved imaging of right-sided leads and increasing the diagnostic yield compared with TEE.


Credibility, credulity, and redistribution.
After raising some doubts for cultural group selection as an explanation of prosocial religiosity, we propose an alternative that views it as a "greenbeard effect." We combine the dynamic constraints on the evolution of greenbeard effects with Iannaccone's (1994) account of strict sects. Our model shows that certain social conditions may foster credulity and prosociality.


Bisucaberin biosynthesis: an adenylating domain of the BibC multi-enzyme catalyzes cyclodimerization of N-hydroxy-N-succinylcadaverine.
The bisucaberin biosynthetic gene cluster has been identified in Vibrio salmonicida and a domain from within the BibC multienzyme encoded by the cluster has been shown to catalyse ATP-dependent dimerisation and macrocyclisation of N-hydroxy-N-succinylcadaverine to form bisucaberin.


A Narrative Review of Pharmacologic and Non-pharmacologic Interventions for Disorders of Consciousness Following Brain Injury in the Pediatric Population.
Traumatic brain injury (TBI) is the most common cause of long-term disability in the United States. A significant proportion of children who experience a TBI will have moderate or severe injuries, which includes a period of decreased responsiveness. Both pharmacological and non-pharmacological modalities are used for treating disorders of consciousness after TBI in children. However, the evidence supporting the use of potential therapies is relatively scant, even in adults, and overall, there is a paucity of study in pediatrics. The goal of this review is to describe the state of the science for use of pharmacologic and non-pharmacologic interventions for disorders of consciousness in the pediatric population.


A new antitumor agent: methyl sulfonium perchlorate of echinomycin.
Newly modified-echinomycin such as S-methylated sulfonium perchlorate of echinomycin (1), monosulfoxide (2), disulfoxid (3) and sulfone (4) have been prepared and evaluated for in vitro biological activities of cytotoxicity against P388, B16 and SNU-16 as well as in vivo antitumor activity against murine leukemia P388 and melanoma B16.


Young donor-graft assisted endothelial keratoplasty (PDEK/DMEK) with epithelial debridement for chronic pseudophakic bullous keratopathy.
The aim of this study was to describe the applicability and report visual outcomes for the treatment of subepithelial fibrosis and anterior stromal scarring in cases of chronic pseudophakic bullous keratopathy (PBK) with epithelial debridement and endothelial keratoplasty (EK) (pre-Descemet endothelial keratoplasty [PDEK]; Descemet membrane endothelial keratoplasty [(DMEK]) using young donor tissue. Prospective, single-centre, interventional study. 6 cases with chronic PBK (> 1 year duration). Case 1 underwent PDEK with glued intraocular lens (IOL) as a single-stage procedure, whereas cases 2 and 3 underwent glued IOL followed by DMEK and PDEK, respectively, as a second-stage procedure. Cases 4 and 6 underwent PDEK, whereas case 5 underwent DMEK. Epithelial debridement was performed in all cases at the time of EK, and young donor grafts were used. The main outcome measures were best spectacle-corrected visual acuity, clearance of corneal scar and haze, central corneal thickness (CCT), specular microscopy, and endothelial cell count (ECC). Postoperatively, all cases demonstrated significant improvement in visual acuity. The mean value of depth of subepithelial haze was 121±71.7 µm and 25.3 ± 19.8 µm in the preoperative and postoperative periods, respectively (p = 0.028). At the 1-month follow-up, the mean preoperative CCT of 676 ± 92.7 µm was reduced to 534.6 ± 21.1µm. At the 6-month follow-up, the mean ECC loss resulting from the procedure was 36.5 ± 10.4%. EK with epithelial debridement performed for the treatment of chronic PBK resulted in significantly improved visual acuity to a functional level, with the clearance of subepithelial fibrosis and anterior stromal scar, in most patients.


Safety and efficacy of microsurgery for complex cranial pathologies in the ultra-geriatric population.
The global increase in the "ultra-geriatric" population (aged 80 years and older) has led to higher demand for neurosurgical procedures in this vulnerable population. The objective was to evaluate the safety and efficacy of advanced microsurgical procedures on ultra-geriatric patients, in our modern era of neurosurgery, anesthesiology, and advanced medical care. The study examined 66 complex cranial procedures, performed on 65 ultra-geriatric patients, who constituted 3.8% of the 4461 consecutive neurosurgical procedures performed by a single neurosurgeon over 14-years in a tertiary care university hospital. Excluded from this study were intra- or extra-axial spontaneous hematomas or traumatic brain injuries, infections, biopsy-only cases and carotid endarterectomies. The most common indication for surgery for the 66 complex cranial procedures were meningiomas (23.9%), followed by gliomas (17.9%), and metastatic brain tumors (17.9%). Postoperative complications occurred in seven procedures (10.60%). No patient deaths were directly caused by intra- or postoperative events, and only one 30-day mortality occurred. All deceased patients had a statistically significant higher American Society of Anesthesiologists (ASA) class (p = 0.024). However, there was no significant correlation between ASA class and modified Rankin scale at discharge (p = 0.238). With the aging global population and increasing life expectancy, the number of ultra-geriatric patients with complex pathologies seeking advanced microsurgical treatment is growing. Therefore, neurosurgeons are confronting a growing number and variety of complex pathologies in ultra-geriatric patients in their daily practice. Regardless of advanced age, microsurgery provides safe and effective treatment, with age alone not being a barrier to proper neurosurgical treatment when other risk factors are adequately modified.


Study on diagnostic value of results of EB virus nucleic acid quantification in whole blood lymphocyte and serum in children with EB virus infection.
The article aims to study the results of EB virus nucleic acid quantification (EBV-DNA) in whole blood lymphocytes to examine whether serum can diagnose EB virus infection in children. Group A consisted of 65 children admitted to the hospital with a probable EB virus infection between February 2017 and February 2018. In the same period of health check-ups, 65 children were randomly selected as Group B. To find out the differences between Group A and Group B, EBV-DNAs in whole blood lymphocyte and serum were detected by quantitative fluorescence assay, and EBV-CA-IgM antibody was detected by enzyme-linked immunosorbent assay. The results demonstrate that Group A had a greater rate of positive EBV-DNAs in whole blood lymphocytes and serum than Group B. EBV-DNA positivity was greater in whole blood lymphocytes of Group A and Group B than in serum. In whole blood lymphocytes from Group A, the positive rate of EBV-DNA and EBV-CA-IgM antibodies was statistically significant. The positive rate of EBV-DNA in whole blood lymphocytes of EBV-infected children is higher than in serum, the suitable specimens for diagnosis should be chosen based on the individual condition of children patients.


Hydrodynamic and direct-current insulator-based dielectrophoresis (H-DC-iDEP) microfluidic blood plasma separation.
Evaluation and diagnosis of blood alterations is a common request for clinical laboratories, requiring a complex technological approach and dedication of health resources. In this paper, we present a microfluidic device that owing to a novel combination of hydrodynamic and dielectrophoretic techniques can separate plasma from fresh blood in a microfluidic channel and for the first time allows optical real-time monitoring of the components of plasma without pre- or post-processing. The microchannel is based on a set of dead-end branches at each side and is initially filled using capillary forces with a 2-μL droplet of fresh blood. During this process, stagnation zones are generated at the dead-end branches and some red blood cells (RBCs) are trapped there. An electric field is then applied and dielectrophoretic trapping of RBCs is used to prevent more RBCs entering into the channel, which works like a sieve. Besides, an electroosmotic flow is generated to sweep the rest of the RBCs from the central part of the channel. Consequently, an RBC-free zone of plasma is formed in the middle of the channel, allowing real-time monitoring of the platelet behavior. To study the generation of stagnation zones and to ensure RBC trapping in the initial constrictions, two numerical models were solved. The proposed experimental design separates up to 0.1 μL blood plasma from a 2-μL fresh human blood droplet. In this study, a plasma purity of 99 % was achieved after 7 min, according to the measurements taken by image analysis. Graphical Abstract Schematics of a real-time plasma monitoring system based on a Hydrodynamic and direct-current insulator-based dielectrophoresis microfluidic channel.


Mouse homolog of the yeast origin recognition complex subunit ORC1 and chromosomal localization of the cognate mouse gene Orc1.
ORC1 encodes a subunit of the eukaryotic origin recognition complex in yeast, which has been shown to play a crucial role in chromosomal DNA replication and transcriptional silencing. We have identified a mouse protein closely related to Saccharomyces cerevisiae ORC1 as well as to the human, Xenopus and Drosophila homologs. MmORC1 has putative cyclin-dependent phosphorylation sites and a nucleotide triphosphate-binding motif. We have mapped the gene locus of the murine Orc1 gene to chromosome 4, band D. Conservation of structures among members of the ORC1-related proteins suggests that these proteins play a key role in the intiation of DNA replication in all eukaryotes.


Enhancement of combustion effect leading to improved performance and exhaust emissions of an SI engine with ferrous oxide and graphite nanoparticles.
The present study was conducted to investigate the effectiveness of new, less toxic, less harmful, and nonmetallic graphite (G) and metallic iron oxide (Fe2O3) nanofuel additives by analyzing experimentally their consequences on exhaust emissions and performance of an air cooled, single cylinder, 4-stroke gasoline engine. Fe2O3 and graphite nanoparticles at 40, 80, and 120 mg/l of gasoline concentrations were mixed with gasoline by means of a magnetic stirrer. Brake power (BP), brake-specific fuel consumption (BSFC), torque (T), brake thermal efficiency (BTE), nitrogen oxides (NOx), carbon monoxide (CO), hydrocarbons (HC), and carbon dioxide (CO2) emissions were the investigated parameters. Experimental results indicated that G-blends showed a higher rise in brake power, brake thermal efficiency and torque and a greater reduction in the brake-specific fuel consumption as compared to that of Fe2O3 fuel blends. Moreover, the G-blends produced less NOx and CO2 than Fe2O3 blends but produced more emissions of CO and HC than that of Fe2O3 blends. On average, G-blends produced 0.46%, 0.71%, and 1.71% more torque, power, and BTE and 2.43%, 1.87%, and 13.39% less brake-specific fuel consumption (BSFC), NOx, and CO2 than Fe2O3 blends, respectively. So, in terms of the eight parameters, four performance parameters (i.e., T, BP, BSFC, BTE), and four engine emission exhaust indicators (i.e., CO, NOx, HC, CO2), graphite nanoparticles showed more positive results for 6 parameters (T, BP, BSFC, BTE, NOx, CO2), while two parameters HC and CO showed negative results with graphite as compared to that of Fe2O3 nanoparticles. So, overall, we conclude that nanoparticles of graphite are more engine and environment friendly than that of iron oxide fuel additives.


Primate learning tasks reveal strong impairments in patients with presenile or senile dementia of the Alzheimer type.
Eight subjects with the likely diagnosis of presenile or senile dementia of the Alzheimer type were tested on two frequently used primate learning tasks: a concurrent object discrimination task and a delayed non-match-to-sample task. In addition, various tests for cognitive, mnemonic, perceptual, and language functions were applied. The results suggest a severe decline of the Alzheimer subjects in all measures when compared with 10 control subjects matched for age, gender, and education. The two animal learning tasks revealed strong impairments, thus demonstrating a high sensitivity for the detection and assessment of human amnesic disorders. Implications of these findings for human neuropsychological, and especially comparative neuropsychological, research are discussed.


Functional studies on the candidate ATPase domains of Saccharomyces cerevisiae MutLalpha.
Saccharomyces cerevisiae MutL homologues Mlh1p and Pms1p form a heterodimer, termed MutLalpha, that is required for DNA mismatch repair after mismatch binding by MutS homologues. Recent sequence and structural studies have placed the NH(2) termini of MutL homologues in a new family of ATPases. To address the functional significance of this putative ATPase activity in MutLalpha, we mutated conserved motifs for ATP hydrolysis and ATP binding in both Mlh1p and Pms1p and found that these changes disrupted DNA mismatch repair in vivo. Limited proteolysis with purified recombinant MutLalpha demonstrated that the NH(2) terminus of MutLalpha undergoes conformational changes in the presence of ATP and nonhydrolyzable ATP analogs. Furthermore, two-hybrid analysis suggested that these ATP-binding-induced conformational changes promote an interaction between the NH(2) termini of Mlh1p and Pms1p. Surprisingly, analysis of specific mutants suggested differential requirements for the ATPase motifs of Mlh1p and Pms1p during DNA mismatch repair. Taken together, these results suggest that MutLalpha undergoes ATP-dependent conformational changes that may serve to coordinate downstream events during yeast DNA mismatch repair.


Transposition of modified latissimus dorsi musculocutaneous flap in the treatment of persistent bronchopleural fistula after posterolateral incision.
The condition of a 51-year-old man was complicated with empyema and bronchopleural fistula (BPF) after left upper lobectomy and thoracoplasty for pulmonary aspergillosis. On the postoperative day (POD) 12, the opened bronchial stump was directly closed and covered with a pedicled pectoralis major muscle flap. On POD 66, an open-window thoracostomy was done, because of empyema with Pseudomonas aeruginosa Two years later, we could fill the empyema cavity, and close the multiple BPFs with the transposition of a modified pedicled musculocutaneous (MC) flap and the additional thoracoplasty to gain good quality of life. Although the MC flap was a proximal part of the latissimus dorsi muscle, which was dissected along the posterolateral incision of the first operation, it could be successfully transplanted to cover the BPFs in the open-window. In some patients with a small open-window on the upper anterior chest wall, the pedicled proximal latissimus dorsi MC flap may be very useful for treating persistent BPFs even after a standard posterolateral incision.


Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13.
Il4 and Il13, closely linked genes, are expressed monoallelically in TH2 cells. Four different approaches (RNA FISH, cultures from Il13T-Il4/Il13-G4 mice, cultures from heterozygous Il13-Il4 double knockout mice, and a highly selected set of BABL/c*CAST/Ei clones displaying strong Il4 allelic bias) were utilized to study monoallelic expression of Il4 and coexpression of Il4 and Il13 on the same chromosome. There was a random probability for expression of one or two Il4 and one or two Il13 alleles; coexpression of cis and trans Il4 and Il13 alleles was equally probable. Histone H3 acetylation of CNS1, located in the Il13-Il4 intergenic region, was permissive for expression of IL-4 and IL-13 but did not determine the degree of their expression. Thus, monoallelism at the Il4 locus is a complex process; expression is linked to opening CNS1 but probability of expression is controlled at other sites. Based on these probabilities, individual cells randomly express Il4 and Il13 alleles.


Response of Long-Tailed Duck (Clangula hyemalis) to the Change in the Main Prey Availability in Its Baltic Wintering Ground.
The long-tailed duck (Clangula hyemalis) is a vulnerable and declining species wintering in the Baltic Sea. The introduction of the invasive fish, the round goby (Neogobius melanostomus), dramatically impacted the benthic macrofauna in hard-bottom habitats, while no significant changes occurred in soft-bottom benthic macrofauna. Therefore, we aimed to assess the extent to which the diet of long-tailed ducks changed in two different bottom types. We analysed the stomach content of 251 long-tailed ducks bycaught in gillnets from 2016 to 2020 in hard- and soft-bottom habitats and compared these results with those published by Žydelis and Ruškyte (2005). The results show that the long-tailed duck experienced a change in diet in hard-bottom habitats, shifting from the blue mussel to Hediste diversicolor, barnacles, and fish. In soft-bottom habitats, their diet remained similar over time and was based on H. diversicolor, a few bivalve species, and Saduria entomon. There was no evidence of significant differences in diet between sex or age. Despite the abovementioned changes in diet, the average body condition of the species did not change over time or between habitats. This confirms that long-tailed ducks have high feeding flexibility and quick species response to changes in prey availability, as they are capable of shifting their diet to new prey.


Attitudes toward active euthanasia among medical students at two German universities.
There has been an ongoing debate about a legalisation of active euthanasia (AE) in Germany. Palliative care education in German medical schools seeks to foster and cultivate a negative attitude toward AE, but little is known about its effectiveness in this respect. The aim of this study was to assess attitudes toward AE among students with and without palliative medicine tuition (PMT). The link to an anonymised online questionnaire was sent out to 1,092 third, fifth and sixth year medical students (YMS) in August-November 2006 at two German universities: university one (U1) with compulsory and additional optional PMT and university two (U2) without any PMT. Thirteen questions addressed active, passive or indirect euthanasia and physician-assisted suicide (statistic: mean +/- SD (range), Wilcoxon, Whitney U Test, significance p < 0.05). Response rate was 17.5%; 59.2% of the questionnaires were returned from U1 and 40.8% from U2; 28.3% of the students were male. Whereas 50% of third YMS at U1 and 36.7% at U2 favoured a legalisation of AE, this was true for 22.4% sixth YMS at U1 and 35.7% at U2. At U1, the number of students who would want to make use of AE for themselves decreased considerably (70%-44.9%) but less at U2; main reasons were 'unbearable suffering' and 'circumstances that lack dignity'. Of all students, 21.1% at U1 and 37.2% at U2 could imagine to perform AE in patients, even though 72.6% at U1 and 78.2% at U2 think its legalisation would promote misuse. The high proportion of pro-AE attitudes gives reason to reconsider both 'standard' and palliative medicine tuition for medical students.


Biomechanical analysis of the distal metaphyseal ulnar shortening osteotomy.
To investigate the effect of a closing wedge osteotomy at the distal ulnar metaphysis on unloading the ulnar side of the wrist. Seven fresh frozen cadaver arms mounted in a wrist simulator were used for the analysis. A 6-degrees-of-freedom load cell was mounted on the distal radius and another on the distal ulna. Radioulnar carpal joint forces and transverse distal radioulnar joint (DRUJ) load were measured at static wrist positions and during dynamic wrist motions before and after the distal metaphyseal ulnar shortening osteotomy (DMUSO) was performed. At each static position, significant decreases in ulnar load were noted after DMUSO. In addition, mean and maximum loads decreased for each dynamic wrist motion. There were no statistically significant differences in transverse forces across the DRUJ after DMUSO. This study showed that DMUSO is an effective way to decrease the load across the ulnocarpal joint. The geometry of the osteotomy and resultant change in the position of the ulnar head did not increase transverse joint reaction forces. This technique is an alternative to open diaphyseal techniques or methods that damage the articular surface of the distal ulna. Clinical studies will be necessary to associate the biomechanical correction noted in this study with clinical symptom improvement.


[Structure-functional organization of the secretin molecule. III. Reverse conformation problem].
A solution of the "reverse conformational problem" for secretin enables one to predict a series of modified synthetic analogs, the spatial structures of which may assume one of the low-energy states of the native hormone.


2.2 A structure of oxy-peroxidase as a model for the transient enzyme: peroxide complex.
The Fe+3-OOH complex of peroxidases has a very short half life, and its structure cannot be determined by conventional methods. The Fe+2-O2 complex provides a useful structural model for this intermediate, as it differs by only one electron and one proton from the transient Fe+3-OOH complex. We therefore determined the crystal structure of the Fe+2-O2 complex formed by a yeast cytochrome c peroxidase mutant with Trp 191 replaced by Phe. The refined structure shows that dioxygen can form a hydrogen bond with the conserved distal His residue, but not with the conserved distal Arg residue. When the transient Fe+3-OOH complex is modelled in a similar orientation, the active site of peroxidase appears to be optimized for catalysing proton transfer between the vicinal oxygen atoms of the peroxy-anion.


Association of racial disparities in the prevalence of insulin resistance with racial disparities in vitamin D levels: National Health and Nutrition Examination Survey (2001-2006).
We tested the hypothesis that racial differences in vitamin D levels are associated with racial disparities in insulin resistance between blacks and whites. Among 3628 non-Hispanic black and white adults in the National Health and Nutrition Examination Survey from 2001 to 2006, we examined the association between race and insulin resistance using the homeostasis assessment model for insulin resistance. We conducted analyses with and without serum 25-hydroxyvitamin D (25[OH]D). We adjusted for age, sex, educational level, body mass index, waist circumference, physical activity, alcohol intake, smoking, estimated glomerular filtration rate, and urinary albumin/creatinine ratio. Blacks had a lower mean serum 25(OH)D level compared with whites (14.6 [0.3] ng/mL vs 25.6 [0.4] ng/mL, respectively; P < .0001). Blacks had a higher odds ratio (OR) for insulin resistance without controlling for serum 25(OH)D levels (OR, 1.67; 95% confidence interval, 1.26-2.20). The association was not significant (OR, 1.28; 95% confidence interval, 0.90-1.82) after accounting for serum 25(OH)D levels. The higher burden of insulin resistance in blacks compared with whites may be partially mediated by the disparity in serum 25(OH)D levels.


Oral anticholinergics and gastric emptying.
The quarternary ammonium antimuscarinic drugs propantheline bromide and clidinium bromide, given orally at the usual therapeutic doses, delayed gastric emptying of a swallowed radiolabeled liquid meal as measured by a gamma camera. Delay of emptying was dose dependent. If an identical meal was given by gastric tube, there was no slowing of emptying by propantheline in the group as a whole. Six subjects who emptied the intubated meal more quickly with placebo had slowed emptying after 30 mg propantheline. In five others, intubation alone slowed gastric emptying while the addition of 30 mg propantheline caused a paradoxical acceleration of gastric emptying. Clidinium bromide, 5 mg, delayed gastric emptying to the same extent as 15 mg propantheline bromide without the marked suppression of salivary secretion induced by the latter.


eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation.
Pancreatic cancer is a devastating disease characterized by treatment resistance and high recurrence rate. Repopulation of surviving tumor cells undergoing radiotherapy is one of the most common reasons for recurrence. Our previous studies have discovered a novel mechanism for repopulation after irradiation that activation of caspase-3 in irradiated tumor cells activates PKCδ/p38 axis to transmit proliferation signals promoting repopulation of surviving tumor cells. Here we found Sox2 expression is up-regulated in irradiated pancreatic cancer cells, which played a major role in tumor cell repopulation after irradiation. Over-expression of Sox2 strongly enhanced the growth-stimulating effect of irradiated dying tumor cells on living tumor cells through a paracrine modality. Furthermore, we identified activated eIF4E, which is phosphorylated by MNK1, as a regulator of Sox2 expression after irradiation, and pharmacologic inhibition of eIF4E with CGP57380 and Ribavirin significantly weakened Sox2-mediated tumor cell repopulation. Finally, we showed the activation of caspase 3/PKCδ/p38/MNK1 signal pathway in irradiated pancreatic tumor cells. Together, we showed a novel pathway regulating Sox2 expression and Sox2 may be a promising target to reduce recurrence due to repopulation of surviving tumor cells after radiotherapy.


Retracted: Study of the Effectiveness of 5G Mobile Internet Technology to Promote the Reform of English Teaching in the Universities and Colleges.
[This retracts the article DOI: 10.1155/2022/3053694.].


Ultrasound guided placement of transperineal prostatic afterloading catheters.
A new method of performing temporary prostate brachytherapy which does not require an open laparotomy is described. This procedure allows dynamic visualization of the placement of 13-gauge (I-125) or 17-gauge (Ir-192) afterloading catheters into the prostate gland via saggital ultrasound imaging. The image enables visualization of the entire path of the catheter as well as cephalad gland movement. The prostate gland, seminal vesicles, bladder neck, urethra, and rectum are easily identified and implanted, if desired, during the procedure. This procedure has been used in 34 patients as an interstitial boost for locally advanced (T2b, T3) prostatic carcinoma following external beam therapy as a means to safely deliver higher doses to the gland. Another eight patients have undergone this procedure as salvage following failure of prior radical prostatectomy or external beam therapy. Very customized dosimetry has been obtained using this technique as a result of the optimal catheter placement achieved under ultrasound guidance, particularly with I-125. Although it is too early to evaluate efficacy, the procedure has been well tolerated and is associated with minimal morbidity to date. This new procedure seems to be an excellent means of safe delivery of higher doses to the gland compared to conventional external beam therapy. Due to the ability to cover the seminal vesicles as well as the afterloading nature of this procedure, a more customized implant is obtained relative to most permanent techniques, and open laparotomy is not required.


Sternoclavicular joint pseudotumor: a clinicopathologic and radiologic study of 25 cases occurring in patients without prior neck dissection.
Pseudotumors of the sternoclavicular joint are rare, poorly characterized pseudoneoplastic lesions previously reported in association with prior neck dissection and thought to result from mechanical instability of the muscles of the shoulder girdle. We report 25 examples of this distinctive process, occurring in patients without a history of neck dissection, typically sent in consultation out of concern for a primary bone or soft-tissue tumor. Cases occurred in 14 women and 11 men (median = 68 years of age) and involved the sternoclavicular joint (17 cases), sternomanubrial joint (2 cases) or other nearby locations (6 cases). The masses ranged from 0.4 to 6.4 cm in size (median = 2.2 cm). Twenty-one patients (84%) had a clinical history of osteoarthritis involving other joints. Clinical follow-up (16 patients; mean = 11.4 months; range = 2-40 months) was uniformly benign, without evidence of recurrent disease. Radiologic review showed changes of osteoarthritis, often with cystic change. Pathologic features included degenerating cartilage, fibrinoid debris, pseudocyst formation, and florid proliferation of myofibroblasts and capillaries. The differential diagnosis of sternoclavicular/sternomanubrial pseudotumors centers around cartilaginous tumors of bone, in particular chondrosarcoma. Careful clinical, radiographic, and pathologic correlations are essential in arriving at the correct diagnosis and avoiding overtreatment.


Quantum-like influence diagrams for decision-making.
This article proposes a novel and comprehensive framework on how to describe the probabilistic nature of decision-making process. We suggest extending the quantum-like Bayesian network formalism to incorporate the notion of maximum expected utility to model human paradoxical, sub-optimal and irrational decisions. What distinguishes this work is that we take advantage of the quantum interference effects produced in quantum-like Bayesian Networks during the inference process to influence the probabilities used to compute the maximum expected utility of some decision. The proposed quantum-like decision model is able to (1) predict the probability distributions found in different experiments reported in the literature by modelling uncertainty through quantum interference, (2) to identify decisions that the decision-makers perceive to be optimal within their belief space, but that are actually irrational with respect to expected utility theory, (3) gain an understanding of how the decision-maker's beliefs evolve within a decision-making scenario. The proposed model has the potential to provide new insights in decision science, as well as having direct implications for decision support systems that deal with human data, such as in the fields of economics, finance, psychology, etc.


High-tech homecare infusion therapies.
Dramatic changes in health care delivery have created an increased reliance on ambulatory care. Adults and children increasingly are receiving infusions of intravascular medication or fluid in the home for a wide array of conditions. Several therapies have been adapted to the home, including chemotherapy, BRMs, TPN, blood components, anti-infectives, analgesics, inotropic agents, and investigational drugs. High-technology therapy in the home mandates safe and reliable vascular access to maximize positive outcomes, independence, and self-care; minimize costs and disruption of daily activities and work schedules; and enhance client and family adjustments and satisfaction. Currently, the four main VADs for vascular access are central venous catheters (CVCs), peripherally inserted central catheters (PICCs, implantable infusion ports, and external or implantable ambulatory infusion pumps.


Male parasitism and intrasexual competition in a burrowing barnacle.
In sexually dimorphic animals, large male body size is often associated with direct interference competition among males for access to females or resources used in reproduction. In constrast, small male body size may be associated with indirect scramble competition among males for temporal or spatial access to females. Minute, "parasitic" males of the acrothoracican barnacleTrypetesa lampas (Hancock) appear to compete with one another for permanent attachment sites on the external body of the female. Several spatial patterns suggest indirect male-male competition: 1) males were consistently aggregated on the anterior surface of the female ovarian disc; 2) the average distance from attached males to the site of insemination correlated positively with local male density; 3) average male body size on a female decreased as a function of male density; 4) the distribution of males on the left and right hand sides of the female ovarian disc was more even than expected, suggesting that males avoided crowded settlement sites. The number of males attached to a female increased with female body size and matched a null model in which males colonized female "targets" of differing areas. These results suggest that competition between males primarily affected settlement sites and male body sizes within, rather than among, females. Male parasitism may have evolved through both sexual selection for efficient access to females (Ghiselin 1974) and natural selection for reduced burrow density in a space-limited habitat (Turner and Yakovlev 1983).


Clinical associations of serum interleukin-17 in systemic lupus erythematosus.
Serum interleukin (IL)-17 concentrations have been reported to be increased in systemic lupus erythematosus (SLE), but associations with clinical characteristics are not well understood. We characterized clinical associations of serum IL-17 in SLE. We quantified IL-17 in serum samples from 98 SLE patients studied cross-sectionally, and in 246 samples from 75 of these patients followed longitudinally over two years. Disease activity was recorded using the SLE Disease Activity Index (SLEDAI)-2k. Serum IL-6, migration inhibitory factor (MIF), and B cell activating factor of the tumour necrosis factor family (BAFF) were also measured in these samples. Serum IL-17 levels were significantly higher in SLE patients compared to healthy donors (P <0.0001). No correlation was observed between serum IL-17 and SLEDAI-2k, at baseline or during longitudinal follow-up. However, we observed that SLEDAI-2k was positively correlated with IL-17/IL-6 ratio. Serum IL-17 was significantly increased in SLE patients with central nervous system (CNS) disease (P = 0.0298). A strong correlation was observed between serum IL-17 and IL-6 (r = 0.62, P <0.0001), and this relationship was observed regardless of disease activity and persisted when integrating cytokine levels over the period observed (r = 0.66, P <0.0001). A strong correlation of serum IL-17 was also observed with serum BAFF (r = 0.64, P <0.0001), and MIF (r = 0.36, P = 0.0016). Serum IL-17 concentration correlates poorly with SLE disease activity but is significantly elevated in patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6 alone to characterize Th17-driven disease, such as SLE. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE.


Workforce cultural factors in TQM/CQI implementation in hospitals.
One of the major obstacles to successful implementation of TQM/CQI in hospitals has been management's failure to consider the workforce cultural situation. This quasi-qualitative study investigates eight workforce cultural factors in seven midwestern hospitals. Results reveal only one of the seven hospitals successfully implementing TQM/CQI.


Analysis of the lignocellulosic components of biomass residues for biorefinery opportunities.
The present study aims to identify the renewable resources available in Brazil such as açai seed, coconut husks, coffee husks, rice husks, eucalyptus sawdust, grass, soy peel, bamboo, banana stems and banana stalks. To identify such renewable energy sources, samples were examined for their physical and chemical characteristics using X-ray diffraction (XRD), proximate and ultimate analyses, thermogravimetric analysis (TGA), calorific value determination, near-infrared (NIR) spectroscopy, UV spectroscopy, high-pH anion-exchange chromatography (HPAEC-PAD) and accelerated solvent extraction (ASE). Among the biomasses, açai and coffee exhibited higher total sugar content, 67.70% and 62.55%, respectively. Sawdust exhibited low ash, along with the highest calorific value and lignin content. The highest glucose contents were observed in bamboo (44.65%) and sawdust (38.80%). The maximum yield for the bioproducts levulinic acid (LA), formic acid (FA) and furfural were estimated; açai exhibited the highest yield of LA and FA, while coffee exhibited the best furfural yield. All of these properties indicate that the residues are potential candidates for bioenergy production.


Altered motivation of effortful decision-making for self and others in subthreshold depression.
Amotivation is a typical feature in major depressive disorders and refers to individuals exhibiting reduced willingness to exert effort for rewards. However, the motivation pattern when deciding whether to exert effort for self versus others in people with depression remains unclear. We conducted a functional magnetic resonance imaging study and employed an adapted Effort-Expenditure for Rewards Task in subthreshold depressive (SD) participants (n = 33) and healthy controls (HC) (n = 32). This required participants to choose between a fixed low-effort/low-reward and a variable high-effort/high-reward option, and then immediately exert effort to obtain corresponding rewards for themselves or for unfamiliar people. Compared with the HC group, the SD group showed blunted activity in the left dorsal anterior cingulate cortex/dorsomedial prefrontal cortex, bilateral anterior insula (AI), and right putamen-left dorsolateral prefrontal cortex functional connectivity when choosing to exert effort for themselves. Additionally, the SD group exhibited increased willingness and greater activation in the bilateral AI when choosing to exert effort for others. Furthermore, these brain activations and functional connectivity were positively related to self-reported motivation. These findings show altered motivation during effort-based decision-making in individuals with the mild depressive state, particularly with higher motivation for others. Thus, this suggests that motivational behaviors and prefrontal-striatal circuitry are altered in individuals with SD, which can be utilized to discover treatment targets and develop strategies to address mental illness caused by motivation disorders.


Chitosan and fish collagen as biomaterials for regenerative medicine.
This chapter focuses and reviews on the characteristics and biomedical application of chitosan and collagen from marine products and advantages and disadvantages of regeneration medicine. The understanding of the production processes of chitosan and collagen and the conformation of these biomaterials are indispensable for promoting the theoretical and practical availability. The initial inflammatory reactions associated with chitosan application to hard and soft tissues need to be controlled before it can be considered for clinical application as scaffold. Further, as chitosan takes too long for biodegradation in vivo, generally it is not suitable for the scaffold for degenerative medicine in especially dental pulp tissue. The collagen extract from the scales of tropical fish has been reported to have a degeneration temperature of 35°C. The properties of biocompatibility and biodegradation of fish atelocollagen are suitable for the scaffold in regenerative medicine.


Effect of dialysate composition on intercompartmental fluid shift.
Effect of dialysate composition on intercompartmental fluid shift and hemodynamics was studied in 12 patients during 1.5 or 2 hours of hemodialysis without net ultrafiltration, using high (H;Na 154 mmol/liter), normal (N;Na 140 mmol/liter) or low (L:Na 126 mmol/liter) concentration dialysate. H dialysate was associated with a small (0.9%) increase in blood volume, a larger increase in plasma volume and a decrease in erythrocyte volume. L dialysate resulted in a 2.3% decrease in blood volume, a larger decrease in plasma volume and an increase in erythrocyte volume. N dialysate gave results which were intermediately between the other two dialysis conditions. There was no difference in the post-dialysis mean arterial pressure between the groups, although heart rate increased more during H dialysis than during the other two conditions. Change in blood and erythrocyte volume correlated significantly with change in plasma Na concentration and osmolality, but not with change in plasma urea concentration. We conclude that dialysate composition affects the movement of water into and out of the plasma and erythrocytes in a manner that can be accounted for by altered plasma concentrations of osmotically active substances.


Discovery of novel inhibitor of human leukocyte common antigen-related phosphatase.
Human leukocyte common antigen-related phosphatase (LAR) may play a role in type 2 diabetes and cancer, and in the development of the nervous system, and it may be an attractive target for the treatment of diabetes and cancer. We identified eight hits from the random screening of LAR D1 with a high-throughput screening assay. Further validation of the eight hits showed that the meD insertion was associated with inhibition of LAR D1D2 and LAR D1Q. These data suggest that the inserted meD peptide influences the interaction of the enzyme and inhibitor, which is consistent with the kinetic catalysis constants of the substrate pNPP. Our data showed that Hit 1, the first published novel inhibitor of LAR, is a competitive inhibitor with a K(i) of 330 nM that displays obvious selectivity for LAR and mouse PTPsigma, but not for other protein tyrosine phosphatases.


Astaxanthin protects mesenchymal stem cells from oxidative stress by direct scavenging of free radicals and modulation of cell signaling.
Recent evidence has shown that mesenchymal stem cells (MSCs) play vital roles in cell therapy of ischemia/hypoxia damaged tissues. However, after the transplantation, they might undergo apoptosis due to oxidative stress. Thus, some strategies have been developed to support stem cells in harsh conditions, including pre-treatment of the cells with antioxidants. Of various antioxidants, in this study, astaxanthin (ATX) was used to protect adipose-derived MSCs against oxidative stress. The MSCs were exposed to different doses of hydrogen peroxide, and then the expression of key genes involved in the redox signaling pathway was studied, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinine oxidoreductase 1 (NQO1). The balance of intracellular reactive oxygen species was detected with the H2DCFDA molecular probe. Additionally, for the detection of apoptosis and protective effect of ATX, the DAPI/Phallacidin and annexin V cell staining were performed. The results of cellular studies revealed that ATX reduced the H2O2-induced cell apoptosis and oxidative stress. Furthermore, after the induction of oxidative stress, the cells' native antioxidants (HO-1 and NQO1) were overexpressed but they were modulated with ATX treatments (p < 0.023). Based on our findings, ATX could increase the expression of Nrf2 as a key transcription factor of antioxidant enzymes (p < 0.05). These findings support the notion that ATX can act as an effective antioxidant in the pre-treatment of MSCs before cell therapy. Thus, to enhance the viability of stem cells during the transplantation in harsh conditions, the concurrent use of ATX in cell therapy modalities is proposed.


Draft Genome Sequence of Bacillus sp. GZT, a 2,4,6-Tribromophenol-Degrading Strain Isolated from the River Sludge of an Electronic Waste-Dismantling Region.
Here, we report the draft genome sequence of Bacillus sp. strain GZT, a 2,4,6-tribromophenol (TBP)-degrading bacterium previously isolated from an electronic waste-dismantling region. The draft genome sequence is 5.18 Mb and has a G+C content of 35.1%. This is the first genome report of a brominated flame retardant-degrading strain.


Contribution of cryopreservation in a mandatory SET policy: analysis of 5 years of application of law in an academic IVF center.
To analyse treatment outcomes after SET law enforcement and to evaluate the contribution of cryopreservation in a SET policy. Embryo transfer cycles performed after the law enforcement (SET period) was retrospectively compared to the cycles performed before the law enforcement (DET period). Pregnancy and delivery rates after fresh transfer of SET and DET periods were comparable (31.7% versus 33.3% and 24.5% versus 26.2%, respectively, NS). Overall twin delivery rate is significantly decreased after the law enforcement (11.3% versus 22.4%, p < 0.001) but not in patients aged 36 to 39 years (20.3% versus 24%, NS). Frozen-thawed embryo cycles allowed similar cumulative pregnancy rate (30.6%, NS). Taking into account all frozen embryos still to be transferred, SET period offers a better overall pregnancy rate than the DET period (36.1% versus 32.3%, p < 0.01). The Belgian law allowed a dramatic reduction of twin deliveries especially for patients under 39 years. Cryopreservation maintains a similar cumulative pregnancy rate.


Evaluation of diffusion measurements reveals radial diffusivity indicative of microstructural damage following acute, mild traumatic brain injury.
Mild TBI, characterized by microstructural damage, often undetectable on conventional imaging techniques, is a pervasive condition that disturbs brain function and can potentially result in long-term deficits. Deciphering the underlying microstructural damage in mild TBI is crucial for establishing a reliable diagnosis and enabling effective therapeutics. Efforts to capture this damage have been extensive, but results have been inconsistent and incomplete. To that effect, we set out to examine the shape of the diffusion tensor in mild TBI during the acute phase of injury. We inspected diffusivity and geometric measurements describing the diffusion tensor's shape and compared mild TBI (N = 34, 20.4-66.6 yo) measurements with those from healthy control (N = 42, 20.7-67.2 yo) participants using voxelwise tract-based spatial statistics. Subsequently, to explore associations between the diffusion measurements in mild TBI, we performed nonparametric statistics and machine learning techniques. Overall, mild TBI displayed a diffuse increase in Dλ2, Dλ3, Dradial, Dmean, and Cspherical, with a diffuse decrease in Afractional, Amode, and Clinear, in addition to no change in Daxial or Cplanar. Most notably, our results provide evidence for Dradial as a potential biomarker for microstructural damage, specifically its main component Dλ2, based on their performance in discriminating between mild TBI and control groups. Afractional was also found to be important for discriminating between groups. Our results revealed the importance of a diffusion measurement often overlooked, Dradial, in assessing TBI and suggest differentiating diffusion measurements has the potential utility to detect variations in the underlying pathophysiology after injury.


Maternal serum markers, characteristics and morbidly adherent placenta in women with previa.
To examine associations with morbidly adherent placenta (MAP) among women with placenta previa. Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236,714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls. In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ⩾95th percentile (⩾2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ⩾95th percentile (⩾1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ⩾2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively). Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.


Candesartan, an angiotensin II type 1 receptor antagonist, inhibits pathological retinal neovascularization by downregulating VEGF receptor-2 expression.
Several studies have examined the anti-angiogenic effects of angiotensin II type 1 (AT(1)) receptor antagonists; however, the mechanisms underlying these effects are currently unclear. In the present study, we examined the efficacy and the mechanism of candesartan, an AT(1) receptor antagonist, in suppressing pathological retinal neovascularization. We used an in vivo murine oxygen-induced retinopathy (OIR) model and also studied the in vitro proliferation and migration of human retinal microvascular endothelial cells (HRMECs) induced by vascular endothelial growth factor (VEGF)-A. The regulation of angiogenesis-associated genes such as hypoxia-inducible factor (HIF-1α), VEGF-A, VEGF receptor-1, and VEGF receptor-2 was evaluated with real-time RT-PCR in the OIR model. In the OIR model, candesartan suppressed the pathological neovascularization in a dose-dependent manner, but did not prevent the physiological angiogenesis. However, candesartan did not inhibit VEGF-A-induced proliferation or migration in HRMECs in the in vitro study. When administered interperitoneally in the OIR model, candesartan reduced the upregulation of VEGF receptor-2 in the retina, but had no effects in the other angiogenesis-related genes, such as HIF-1α, VEGF-A, and VEGF receptor-1. These findings indicate that candesartan inhibited the retinal pathological neovascularization, at least in part, by suppressing the expression of VEGF receptor-2, independent of VEGF signaling cascade. Therefore, candesartan may be a useful therapeutic target for the inhibition of retinal neovascularization that has a low risk of serious side effects.