Enhanced piezoresponse of highly aligned electrospun poly(vinylidene fluoride) nanofibers.
Well-ordered nanostructure arrays with controlled densities can potentially improve material properties; however, their fabrication typically involves the use of complicated processing techniques. In this work, we demonstrate a uniaxial alignment procedure for fabricating poly(vinylidene fluoride) (PVDF) electrospun nanofibers (NFs) by introducing collectors with additional steps. The mechanism of the observed NF alignment, which occurs due to the concentration of lateral electric field lines around collector steps, has been elucidated via finite-difference time-domain simulations. The membranes composed of well-aligned PVDF NFs are characterized by a higher content of the PVDF β-phase, as compared to those manufactured from randomly orientated fibers. The piezoelectric energy harvester, which was fabricated by transferring well-aligned PVDF NFs onto flexible substrates with Ag electrodes attached to both sides, exhibited a 2-fold increase in the output voltage and a 3-fold increase in the output current as compared to the corresponding values obtained for the device manufactured from randomly oriented NFs. The enhanced piezoresponse observed for the aligned PVDF NFs is due to their higher β-phase content, denser structure, smaller effective radius of curvature during bending, greater applied strain, and higher fraction of contributing NFs.


RhoA balances microglial reactivity and survival during neuroinflammation.
Microglia are the largest myeloid cell population in the brain. During injury, disease, or inflammation, microglia adopt different functional states primarily involved in restoring brain homeostasis. However, sustained or exacerbated microglia inflammatory reactivity can lead to brain damage. Dynamic cytoskeleton reorganization correlates with alterations of microglial reactivity driven by external cues, and proteins controlling cytoskeletal reorganization, such as the Rho GTPase RhoA, are well positioned to refine or adjust the functional state of the microglia during injury, disease, or inflammation. Here, we use multi-biosensor-based live-cell imaging approaches and tissue-specific conditional gene ablation in mice to understand the role of RhoA in microglial response to inflammation. We found that a decrease in RhoA activity is an absolute requirement for microglial metabolic reprogramming and reactivity to inflammation. However, without RhoA, inflammation disrupts Ca2+ and pH homeostasis, dampening mitochondrial function, worsening microglial necrosis, and triggering microglial apoptosis. Our results suggest that a minimum level of RhoA activity is obligatory to concatenate microglia inflammatory reactivity and survival during neuroinflammation.


Continuous O2-Evolving MnFe2O4 Nanoparticle-Anchored Mesoporous Silica Nanoparticles for Efficient Photodynamic Therapy in Hypoxic Cancer.
Therapeutic effects of photodynamic therapy (PDT) are limited by cancer hypoxia because the PDT process is dependent on O2 concentration. Herein, we design biocompatible manganese ferrite nanoparticle-anchored mesoporous silica nanoparticles (MFMSNs) to overcome hypoxia, consequently enhancing the therapeutic efficiency of PDT. By exploiting the continuous O2-evolving property of MnFe2O4 nanoparticles through the Fenton reaction, MFMSNs relieve hypoxic condition using a small amount of nanoparticles and improve therapeutic outcomes of PDT for tumors in vivo. In addition, MFMSNs exhibit T2 contrast effect in magnetic resonance imaging (MRI), allowing in vivo tracking of MFMSNs. These findings demonstrate great potential of MFMSNs for theranostic agents in cancer therapy.


The influence of quality maternity waiting homes on utilization of facilities for delivery in rural Zambia.
Residential accommodation for expectant mothers adjacent to health facilities, known as maternity waiting homes (MWH), is an intervention designed to improve access to skilled deliveries in low-income countries like Zambia where the maternal mortality ratio is estimated at 398 deaths per 100,000 live births. Our study aimed to assess the relationship between MWH quality and the likelihood of facility delivery in Kalomo and Choma Districts in Southern Province, Zambia. We systematically assessed and inventoried the functional capacity of all existing MWH using a quantitative facility survey and photographs of the structures. We calculated a composite score and used multivariate regression to quantify MWH quality and its association with the likelihood of facility delivery using household survey data collected on delivery location in Kalomo and Choma Districts from 2011-2013. MWH were generally in poor condition and composite scores varied widely, with a median score of 28.0 and ranging from 12 to 66 out of a possible 75 points. Of the 17,200 total deliveries captured from 2011-2013 in 40 study catchment area facilities, a higher proportion occurred in facilities where there was either a MWH or the health facility provided space for pregnant waiting mothers compared to those with no accommodations (60.7% versus 55.9%, p <0.001). After controlling for confounders including implementation of Saving Mothers Giving Life, a large-scale maternal health systems strengthening program, among women whose catchment area facilities had an MWH, those women with MWHs in their catchment area that were rated medium or high quality had a 95% increase in the odds of facility delivery than those whose catchment area MWHs were of poor quality (OR: 1.95, 95% CI 1.76, 2.16). Improving both the availability and the quality of MWH represents a potentially useful strategy to increasing facility delivery in rural Zambia. The Zambia Chlorhexidine Application Trial is registered at Clinical Trials.gov (identifier: NCT01241318).


Capecitabine Extends Survival for Biliary Tract Cancer.
Based on results of the phase III BILCAP study, adjuvant capecitabine should become standard treatment for patients with biliary tract cancer. Among 430 patients who were treated according to the study protocol, capecitabine was associated with a 25% lower risk of death than observation.


Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries.
Zidovudine (AZT) is an antiretroviral drug that is a substrate of active efflux transporters (AETs) that extrude the drug from the central nervous system (CNS) and macrophages, which are considered to be sanctuaries of HIV. The conjugation of AZT to ursodeoxycholic acid is known to produce a prodrug (UDCA-AZT) that is able to elude the AET systems, indicating the potential ability of this prodrug to act as a carrier of AZT in the CNS and in macrophages. Here, we demonstrate that UDCA-AZT is able to permeate and remain in murine macrophages with an efficiency twenty times higher than that of AZT. Moreover, we propose the nasal administration of this prodrug in order to induce its uptake into the CNS. Chitosan chloride-based microparticles (CP) were prepared by spray-drying and were characterized with respect to size, morphology, density, water uptake and the dissolution profile of UDCA-AZT. The CP sample was then nasally administered to rats. All in vitro and in vivo measurements were also performed for a CP parent physical mixture. The CP sample was able to increase the dissolution rate of UDCA-AZT and to reduce water uptake with respect to its parent physical mixture, inducing better uptake of UDCA-AZT into the cerebrospinal fluid of rats, where the prodrug can act as an AZT carrier in macrophages.


Propranolol and thyroid hormone metabolism.
Propranolol decreases plasma T3 and increases plasma rT3 in a dose-dependent manner due to a decreased production rate of T3 and a decreased metabolic clearance rate of rT3, respectively, caused by inhibition of the conversion of T4 into T3 and of rT3 into 3,3'-T2. This inhibition of 5'-deiodination is not secondary to inhibition of thyroid hormone transport across the plasma membrane. Propranolol and its major metabolite, 4-hydroxypropranolol, are not directly responsible for these effects, but an unidentified metabolite of propranolol might be involved. beta-blockers ameliorate clinical symptoms and signs of thyrotoxicosis independent of the decrease of plasma 13, that is confined to beta-blockers with membrane-stabilizing activity, such as propranolol and alprenolol. The decrease of plasma T3, however, appears responsible for some of the metabolic responses to beta-blockers.


Role of FeS Catalyst in the Hydromodification of Lignite in a Subcritical Water-CO System.
The impacts of FeS catalysts on the hydromodification and structural evolution of lignite were investigated using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and X-ray photoelectron spectroscopy. The results indicate that the caking property of lignite can be significantly improved in the presence of the FeS catalyst. When 6.0 wt % FeS was added, the maximum caking index (G RI) of modified coal reached 95. During the hydromodification, FeS has little effect on the intrinsic water gas shift reaction, but it can increase the CO conversion by promoting the decomposition and hydrogenation of coal so that more active hydrogen is generated and introduced into modified coal. FeS is conducive to the rupture of distal aliphatic groups in the extractible solutes, which promotes the entrance of hydrogen into the aromatic nucleus (Har) and α positions (Hα) of asphaltenes and β positions (Hβ) of preasphaltenes. After the catalytic hydromodification, the longer side chains or bridge bonds break and are hydrogenated to form the aliphatic structures with a shorter chain or a higher branched degree. Meanwhile, more oxygen-containing functional groups were removed along with the reduction of volatiles in the modified coal. The synergistic effect of FeS on these factors is favorable for the generation of plastic materials, which contributes to the development of the caking property of lignite.


[Antimicrobial susceptibility and resistance patterns of Staphylococcus aureus isolated from patients and carriers in Valdivia city, Chile].
In vitro susceptibility of nosocomial and community acquired strains of Staphylococcus aureus must be periodically evaluated because of its continuous evolution. To know the antimicrobial susceptibility of S. aureus isolated in Valdivia, to determine the prevalence of methicillin resistance and global patterns of resistance and to compare the evolution of the susceptibility along the years. A total of 278 S. aureus strains were evaluated: 136 obtained from hospitalized patients, 50 belonged to outpatients and 92 to healthy carriers. Antimicrobial agents tested were: penicillin, oxacillin, vancomycin, gentamycin, ciprofloxacin, lincomycin and erythromycin. Thirty three, 28 and 1.1% of strains isolated from hospitalized, outpatients and carriers, respectively, were methicillin-resistant. Six resistance patterns were found. No vancomycin resistant strain was isolated. It is worrisome that 2% of S. aureus strains obtained from hospitalized patients showed intermediate resistance to vancomycin.


Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women.
Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (P< 0·05, time × trial interaction), and FMD responses at 120 min were significantly greater in the NOP-47 trial compared with placebo (4·3 (sem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (P< 0·05). Serum insulin increased at 15, 30 and 60 min (P< 0·001) following NOP-47 ingestion. No changes were observed between the trials for plasma NO∙ and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey.


OxyR: a molecular code for redox-related signaling.
Redox regulation has been perceived as a simple on-off switch in proteins (corresponding to reduced and oxidized states). Using the transcription factor OxyR as a model, we have generated, in vitro, several stable, posttranslational modifications of the single regulatory thiol (SH), including S-NO, S-OH, and S-SG, and shown that each occurs in vivo. These modified forms of OxyR are transcriptionally active but differ in structure, cooperative properties, DNA binding affinity, and promoter activities. OxyR can thus process different redox-related signals into distinct transcriptional responses. More generally, our data suggest a code for redox control through which allosteric proteins can subserve either graded (cooperative) or maximal (noncooperative) responses, and through which differential responsivity to redox-related signals can be achieved.


Dexon versus conventional sutures in hernia repair.
An unselected study of 87 inguinal herniorrhapies was carried out over a 2-year period using polyglycolic acid (Dexon) sutures in 46 procedures and conventional sutures in the remaining 41. Tissue reaction was the same with both types of suture; however, the incidence of recurrence was lower with the use of conventional sutures. This study has not confirmed the superiority of Dexon sutures reported in other studies.


Transcriptomic Analysis of THP-1 Cells Exposed by Monosodium Urate Reveals Key Genes Involved in Gout.
Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work. The objective of the study was to analyze and validate potential therapeutic targets and biomarkers in THP-1 cells that were exposed to MSU. THP-1 cells were exposed to MSU. The inflammatory effect was characterized, and RNA-Seq analysis was then carried out. The differential genes obtained by RNA-Seq were analyzed with gene expression omnibus (GEO) series 160170 (GSE160170) gout-related clinical samples in the GEO database and gout-related genes in the GeneCards database. From the three analysis approaches, the genes with significant differences were verified by the differential genes' transcription levels. The interaction relationship of long non-coding RNA (lncRNA) was proposed by ceRNA network analysis. MSU significantly promoted the release of IL-1β and IL-18 in THP-1 cells, which aggravated their inflammatory effect. Through RNA-Seq, 698 differential genes were obtained, including 606 differential mRNA and 92 differential `LncRNA. Cross-analysis of the RNA-Seq differential genes, the GSE160170 differential genes, and the gout-related genes in GeneCards revealed a total of 17 genes coexisting in the tripartite data. Furthermore, seven differential genes-C-X-C motif chemokine ligand 8 (CXCL8), C-X-C motif chemokine ligand 2 (CXCL2), tumor necrosis factor (TNF), C-C motif chemokine ligand 3 (CCL3), suppressor of cytokine signaling 3 (SOCS3), oncostatin M (OSM), and MIR22 host gene (MIR22HG)-were verified as key genes that analyzed the weight of genes in pathways, the enrichment of inflammationrelated pathways, and protein-protein interaction (PPI)nodes combined with the expression of genes in RNA-Seq and GSE160170. It is suggested that MIR22HG may regulate OSM and SOCS3 through microRNA 4271 (miR-4271), OSM, and SOCS3m; CCL3 through microRNA 149-3p (miR-149-3p); and CXCL2 through microRNA 4652-3p (miR-4652-3p). The potential of CXCL8, CXCL2, TNF, CCL3, SOCS3, and OSM as gout biomarkers and MIR22HG as a therapeutic target for gout are proposed, which provide new insights into the mechanisms of gout biomarkers and therapeutic methods.


Immunization with rough mutants of Salmonella minnesota: protective activity of IgM and IgG antibody to the R595 (Re chemotype) mutant.
We evaluated the immunoglobulin class responsible for the protective activity in serum obtained from humans and rabbits after immunization with the R595 (Re chemotype) mutant of Salmonella minnesota. Whole serum obtained before immunization and the IgG and IgM fractions failed to protect mice against lethal challenge with viable Klebsiella pneumoniae or Morganella morganii or with Salmonella typhi lipopolysaccharide (LPS). The protective activity of postimmunization serum resided solely in IgM antibody, whereas IgG antibody exhibited no protective activity. IgM antibody to the Re mutant was protective against bacterial challenge with both test strains of bacteria and S. typhi LPS. IgM antibody, at approximately the same concentration present in postimmunization serum, increased the LD50 of K. pneumoniae from less than 8.0 x 10(2) to greater than 2.0 x 10(4). These findings indicate that commercially prepared human IgG with high titers of antibody to antigens of the core portion of LPS would have little clinical utility.


Doppler Systolic Signal Void in Hypertrophic Cardiomyopathy: Apical Aneurysm and Severe Obstruction without Elevated Intraventricular Velocities.
In patients with hypertrophic cardiomyopathy (HCM), akinetic apical aneurysms are associated with ventricular tachycardia, heart failure, apical thrombus, and mortality. The cause of apical aneurysms remains unresolved, and there is controversy about prevalence and significance of mid-left ventricular (LV) obstruction, often present in these patients. The aim of this study was to test the hypothesis that low velocities in patients with aneurysms are due to near complete cessation of mid-LV flow, characteristically marked by a Doppler signal void. This was a retrospective analysis of 39 patients with HCM with segmental hypertrophy of the mid left ventricle and complete systolic emptying at the mid-LV level. The severity of dynamic obstruction was evaluated by measuring the time during which cross-sectional mid-LV cavity area was <1 cm(2). Presence or absence of an LV Doppler midsystolic signal void was determined. Akinetic apical aneurysms were present in 21 patients. The duration of two-dimensional mid-LV short-axis complete emptying was longer in patients with akinetic apical aneurysms (194 ± 45 vs 148 ± 63 msec, P = .013), nearly 50% of systole. Midsystolic signal voids were seen only in patients with akinetic apical aneurysms (P < .001), present in 86%. In patients with akinetic aneurysms, there was a strong correlation between the duration of the systolic signal void and the proportion of systole with complete emptying < 1 cm(2) (r = 0.704; P = .001). Complete emptying < 1 cm(2) for ≥ 38% of systole was associated with akinetic aneurysm (odds ratio, 9.35; P < .004). Patients with akinetic apical aneurysm HCM have near complete cessation of flow across severe dynamic mid-LV obstruction for nearly 50% of systole. This explains how the adverse effects of obstruction may occur without high velocities on echocardiography.


The cationic cytokine IL-26 differentially modulates virus infection in culture.
Interleukin-26 (IL-26) belongs to the IL-10 cytokine family, is produced by activated T cells, and targets epithelial target cells for signal transduction. Here, we describe the IL-26 effects on the infection of culture cells with recombinant vesicular stomatitis virus (VSV), human cytomegalovirus (HCMV), and herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. After pre-incubation with recombinant IL-26 and at low multiplicity of infection, VSV showed strongly enhanced infection and replication rates as measured for infectivity, for transcript levels, and for protein expression. Control proteins did not affect VSV infection. The IL-26 effect was independent of the IL-26 receptor and neutralized by anti-IL-26 serum. Pre-incubation of VSV was much more efficient than pre-incubation of the target cells to enhance virus infection. IL-26 increased virus adsorption to target cells as shown by quantitative reverse-transcription PCR. In contrast, the infection of IL-26-treated human fibroblasts with HCMV was inhibited and the infection by HSV-1 was not altered by IL-26. Thus, IL-26 differentially modulates the infection by different enveloped viruses.


Prognostic significance of the Gustave Roussy immune (GRIm) score in cancer patients: a meta-analysis.
The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients. Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis. Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73-2.48; p < 0.0001; I2 = 62%) and progression-free survival (HR = 1.42; 95%CI: 1.22-1.66; p < 0.0001; I2 = 36%). The prognostic values of GRIm on overall survival and progression-free survival were observed across various tumour types and tumour stages. Sensitivity analysis supported the stability and reliability of the above results. Our evidence suggested that the GRIm score could be a valuable prognostic marker in cancer patients, which can be used by clinicians to stratify patients and formulate individualized treatment plans.


Perfluorooctanesulfonate (PFOS) Conversion from N-Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) in male Sprague Dawley rats after inhalation exposure.
Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) was one of the key building blocks for many of the perfluorooctanesulfonyl-based chemistry and laboratory studies have shown that EtFOSE can metabolically degrade to perfluorooctanesulfonate (PFOS). Non-occupational contribution sources to PFOS are thought to occur in general population via diets, drinking water, air and dust. For workers, however, the exposure route was mostly airborne and the exposure source was predominantly to precursor compounds such as EtFOSE. We undertook this study to investigate how much EtFOSE was converted to PFOS in the serum for male rats after 6h of exposure to EtFOSE vapor (whole body) at ambient temperature, which simulated a work place exposure scenario. There were no abnormal clinical observations and all rats gained weight during study. Interim tail-vein blood samples, collected up to 21 days after exposure, were analyzed for Et-FOSE and PFOS concentrations by LC-MS/MS. Upon inhalation exposure, the biotransformation of EtFOSE to PFOS in serum in the male rats was rapid and very little EtFOSE was detected in the serum within 24h after EtFOSE exposure. The highest conversion to PFOS in serum after exposure to EtFOSE vapor appeared to occur between Day 8-14 post exposure. Considering the potential surface and fur adsorption of test compound in the whole-body exposure system, our data would support that at least 10% of the inhaled EtFOSE was biotransformed to PFOS in the serum based on the range of lower 95% CI (confidence interval) values. This information is valuable because it quantitatively translates EtFOSE exposure into serum PFOS concentration, which serves as a matrix for internal dosimetry (of PFOS exposure) that can be used as an anchor across species as well as between different exposure routes.


Y-nitinol airway stent for management of central airway compression due to metastatic colon cancer.
Tumor masses in the area between the esophagus and the tracheobronchial tree can lead to complications involving both systems, mainly strictures and compressions. Malignant esophageal strictures are nowadays often treated by insertion of a metal stent which, however, can cause airway compression especially in the proximal area. We present here a new method of creating a Y-stent out of two self-expandable tracheal nitinol stents, utilizing fiber bronchoscopy, in a 55-year-old woman with advanced colon cancer metastastic to the mediastinum. The endo-Y-stent technique can be performed with the patient under sedation and having topical anesthesia. The opening through which the second tracheal stent must be placed for the Y construction is created by laser. In this case, the patient suffered from airway compression which was efficiently relieved by this method. Within a short time the endo-Y-stent provides effective restoration and maintenance of airway patency in patients with tumor compression in the region of the esophagus and airway, and in those with airway compression following esophageal stenting. Expertise in both stent implantation and laser application is, however, mandatory.


A case of T-tube dislocation.
In environments where endoscopic retrograde cholangio-pancreatogram (ERCP) services may at time be limited or unavailable, the surgeon must also decide between the insertion of a conventional T-tube or primary choledochorrhaphy when it is operatively perceived that the common bile duct (CBD) has been adequately cleared. Where the hospital stay of the patients with a T-tube in situ is prolonged, there is a higher incidence of postoperative bacteraemia with a moderate morbidity from biliary leakage after T-tube withdrawal. We report here a case as well as methods designed to prevent tube dislocation and alternatives to T-tube insertion after choledochotomy, whether performed open or laparoscopically.


Subchronic inhalation toxicity of morpholine in rats.
The inhalation toxicity of 25-, 100-, and 250-ppm morpholine was investigated by 6 hr/day, 5 day/week exposures to Sprague-Dawley rats for 13 weeks. Irritant effects of morpholine exposures were evident mostly in the high exposure group; a reddish discharge was observed around the nose and mouth in the 250-ppm group rats after the first week; salivation was also observed. Ten rats/sex/dose level were sacrificed after 7 weeks. The high-level (250-ppm) exposure resulted in focal erosion and focal squamous metaplasia of the maxilloturbinates; effects were observed in 6/10 male rats and 2/10 female rats. There was also a sporadic increase of secretions in the Harderian gland sections. Almost all high-level rats sacrificed after 13 weeks demonstrated comparable effects; the lesions, which were increased in incidence and severity, involved the nasal septum and anterior nasal cavities in addition to the nasoturbinates and maxilloturbinates. Lesions of chronic murine pneumonia were increased in severity in the 250-ppm group. The only compound-related histomorphologic alterations observed in the 100-ppm group consisted of focal necrosis and necrotic cell debris in the nasal cavity of two female rats at terminal sacrifice. No exposure related effects were observed in the 25-ppm group. No significant compound-related effects on body weight, clinical chemistry, hematology, or organ weight data were observed.


Antioxidant and Anti-Inflammatory Activities of Buffalo Milk δ-Valerobetaine.
δ-Valerobetaine (δVB), a constitutive metabolite of ruminant milk, is produced in the rumen from free dietary Nε- trimethyllysine occurring ubiquitously in vegetable kingdom. The biological role of δVB is poorly known. Here, the antioxidant and anti-inflammatory potential of buffalo milk δVB was tested in vitro during high-glucose (HG)-induced endothelial damage. Results indicated that δVB (0.5 mM) ameliorated the HG cytotoxicity (0.57 ± 0.02 vs 0.41 ± 0.018 O.D. ( P < 0.01). Interestingly, buffalo milk extracts enriched with δVB showed improved significant efficacy in decreasing reactive oxygen species, lipid peroxidation, and cytokine release during HG treatment compared to milk extracts alone ( P < 0.05). It is noteworthy that δVB reduced the HG-activated inflammatory signal by modulating SIRT1 (0.96 ± 0.05 vs 0.85 ± 0.04 AU), SIRT6 (0.82 ± 0.04 vs 0.61 ± 0.03 AU), and NF-κB (0.85 ± 0.03 vs 1.23 ± 0.03 AU) ( P < 0.05). On the whole, our data show the first evidence of δVB efficacy in reducing endothelial oxidative stress and inflammation, suggesting a potential role of this betaine as a novel dietary compound with health-promoting properties.


Bone marrow scintigraphy in breast cancer.
Bone marrow scintigrams (BMS) have been performed in 101 women with histologically proven breast cancer (36 stage IV among them at the time of the first investigation, follow-up examinations available in 41, disease evolution observed in 17). They have been compared to conventional bone scintigram (CBS) as well as to radiological, clinical, biological and follow-up data obtained in the same patients. Only three (7.4%) out of the 41 patients with radiologically or/and histologically proven skeletal metastasis had normal BMS and 33 had corresponding bone marrow scintigraphic defects (BMS ++). On the other hand, only three patients of the 32 with normal BMS had documented skeletal abnormalities. Abnormal bone marrow extension, observed in 61.4% of the patients (62/101), seems to represent a reaction of the reticulo-endothelial system to the disease dissemination - even microscopic - and, as such, to have prognostic implications. As BMS demonstrated skeletal invasion earlier or more precisely than CBS in ten cases, the technique appears of value and of interest in breast cancer management.


Variability in inorganic As, Sb and Tl species concentrations in waters and bottom sediments of the Kłodnica River (Poland).
The study describes the application of new methodologies for the simultaneous determination of As(III)/As(V), Sb(III)/Sb(V) and Tl(I)/Tl(III) ions in waters and bottom sediments of the Kłodnica River (Poland) with the hyphenated technique of high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) . Time and spatial correlations were determined in the changes of total and speciation concentrations of the above-mentioned analytes in Kłodnica river in 2012. The developed methodologies demonstrate high selectivity and limits of quantification at the level of 0.009-0.120 µg/L. Their repeatability, precision and recovery are appropriate for trace analyses of environmental samples. Time and spatial correlations, and concentrations of inorganic As, Sb and Tl ions demonstrated high variability both in water and bottom sediments.


QTL mapping for a trade-off between leaf and bud production in a recombinant inbred population of Microseris douglasii and M. bigelovii (Asteraceae, Lactuceae): a potential preadaptation for the colonization of serpentine soils.
The different response to growth on serpentine soil is a major autecological difference between the annual asteracean species Microseris douglasii and M. bigelovii, with nearly non-overlapping distribution ranges in California. Early flowering and seed set is regarded as a crucial character contributing to escape drought and thus is strongly correlated with survival and reproductive success on serpentine as naturally toxic soil. M. bigelovii (strain C94) from non-serpentine soil produces more leaves at the expense of bud production in the first growing phase than M. douglasii (B14) from serpentine soil. A QTL mapping study for this trade-off and for other growth-related traits was performed after six generations of inbreeding (F7) from a single interspecific hybrid between B14 and C94 on plants that were grown on serpentine and alternatively on normal potting soil. The trade-off is mainly correlated with markers on one map region on linkage group 03a (lg03a) with major phenotypic effects (phenotypic variance explained [PVE] = 18.8 - 31.7 %). Plants with the M. douglasii allele in QTL-B1 (QTL-NL1) produce more buds but fewer leaves in the first 119 days on both soil types. Three modifier QTL could be mapped for bud and leaf production. In one modifier (QTL-B2 = QTL-NL4) the M. douglasii allele is again associated with more buds but fewer leaves. QTL mapped for bud set in the F6 co-localize with QTL-B1 (major QTL) and QTL-B3. Two additional QTL for leaf length and red coloration of leaves could be mapped to one map region on lg03a. Co-localization of the two QTL loci with major phenotypic effects on bud and leaf production strongly suggests that a major genetic locus controls the trade-off between the two adaptive traits. The importance of mutational changes in major genes for the adaptation to stressful environments is discussed.


Complete Genome Sequence of a Foot-and-Mouth Disease Virus of Serotype O, Isolated from Gochang, Republic of Korea, in 2016.
The complete genome sequence of a foot-and-mouth disease (FMD) serotype O virus isolated from Gochang, Republic of Korea, is reported here.


Genome-wide identification of the potato WRKY transcription factor family.
WRKY transcription factors play pivotal roles in regulation of stress responses. This study identified 79 WRKY genes in potato (Solanum tuberosum). Based on multiple sequence alignment and phylogenetic relationships, WRKY genes were classified into three major groups. The majority of WRKY genes belonged to Group II (52 StWRKYs), Group III had 14 and Group I consisted of 13. The phylogenetic tree further classified Group II into five sub-groups. All StWRKY genes except StWRKY79 were mapped on potato chromosomes, with eight tandem duplication gene pairs and seven segmental duplication gene pairs found from StWRKY family genes. The expression analysis of 22 StWRKYs showed their differential expression levels under various stress conditions. Cis-element prediction showed that a large number of elements related to drought, heat and salicylic acid were present in the promotor regions of StWRKY genes. The expression analysis indicated that seven StWRKYs seemed to respond to stress (heat, drought and salinity) and salicylic acid treatment. These genes are candidates for abiotic stress signaling for further research.


An evidence-based approach to the management of hematuria in children in the emergency department.
Hematuria is defined as an abnormal number of red blood cells in urine. Even a tiny amount of blood (1 mL in 1000 mL of urine) is sufficient to make urine appear pink or red. In the pediatric population, the majority of etiologies are benign and often asymptomatic. However, hematuria may also be a sign of renal pathology, local infection, or systemic disease. Hematuria can be differentiated into 2 categories: macroscopic hematuria (visible to the naked eye) and microscopic hematuria (> 5 red blood cells/high-powered field on urinalysis). This review will outline the current literature regarding evaluation and management of pediatric patients who present to the emergency department with hematuria. Obtaining a thorough history and the appropriate diagnostic tests will be discussed in depth.


A comparative study of antibody response, virus neutralization efficiency & metabolites in SARS-CoV-2-infected adults & children.
COVID-19 has been a global pandemic since early 2020. It has diverse clinical manifestations, but consistent immunological and metabolic correlates of disease severity and protection are not clear. This study was undertaken to compare seropositivity rate, antibody levels against nucleocapsid and spike proteins, virus neutralization and metabolites between adult and child COVID-19 patients. Plasma samples from naïve control (n=14) and reverse transcription (RT)-PCR positive COVID-19 participants (n=132) were tested for reactivity with nucleocapsid and spike proteins by ELISA, neutralization of SARS-CoV-2 infectivity in Vero cells and metabolites by [1]H nuclear magnetic resonance (NMR) spectroscopy. An ELISA platform was developed using nucleocapsid and spike proteins for COVID-19 serosurvey. The participants showed greater seropositivity for nucleocapsid (72%) than spike (55.3%), and males showed higher seropositivity than females for both the proteins. Antibody levels to both the proteins were higher in intensive care unit (ICU) than ward patients. Children showed lower seropositivity and antibody levels than adults. In contrast to ICU adults (81.3%), ICU children (33.3%) showed lower seropositivity for spike. Notably, the neutralization efficiency correlated with levels of anti-nucleocapsid antibodies. The levels of plasma metabolites were perturbed differentially in COVID-19 patients as compared with the naive controls. Our results reflect the complexity of human immune response and metabolome to SARS-CoV-2 infection. While innate and cellular immune responses are likely to be a major determinant of disease severity and protection, antibodies to multiple viral proteins likely affect COVID-19 pathogenesis. In children, not adults, lower seropositivity rate for spike was associated with disease severity.


Artificial ion channel biosensor in human immunodeficiency virus gp41 drug sensing.
An ion channel biosensor is described for label-free detection of inhibitors which bind to the coiled coil domain of human immunodeficiency virus type 1 gp41. gp41 is the viral transmembrane glycoprotein responsible for fusion between HIV-1 and host cells. The N-terminal coiled coil domain binds three antiparallel C-heptad repeat peptides in the six helix bundle structure of trimeric gp41 that forms during fusion. Compounds able to prevent six-helix bundle formation by binding to the gp41 coiled coil could inhibit fusion and have important therapeutic potential. We have immobilized on gold a positively charged metallopeptide mimic of a section of the gp41 coiled coil containing a hydrophobic pocket suitable for small molecule binding. We demonstrate that the resulting sensor is able to transmit a current in the presence of negatively charged redox marker ions, therefore acting as an artificial ion channel. The electrochemical signal, measured by cyclic voltammetry, was modulated by specific analyte binding to the coiled coil. Nanomolar quantities of peptides and small molecules that bind in the hydrophobic pocket could be selectively detected, providing a method for label-free detection of binding to gp41.


Photocleavage of DNA and photofootprinting of E. coli RNA polymerase bound to promoter DNA by azido-9-acridinylamines.
The long-wavelength ultraviolet (lambda approximately 420 nm) radiation induced reaction between 6-azido-2-methoxy-9-acridinylamines and supercoiled plasmid DNA results in single strand scissions and formation of covalent adducts (ratio approximately 1:10). By treating azidoacridine-photomodified DNA with piperidine at 90 degrees C, additional strand scissions are observed in a complex sequence dependent manner with an overall preference for T greater than or equal to G greater than C much greater than A. The resulting DNA fragments migrate as 5'-phosphates in polyacrylamide gels. Photofootprinting of the binding site of RNA-polymerase on promoter DNA is demonstrated with an azido-9-acridinylamino-octamethylene-9-aminoacridine. Similar experiments using 9-amino-6-azido-2-methoxyacridine indicate that this reagent recognizes changes in the DNA conformation induced by RNA polymerase binding, in relation to open complex formation.


Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan.
Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored. A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR-29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT-PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR<30mg/g; N=12); microalbuminuria (30mg/g<ACR<300mg/g; N=17) and overt proteinuria (ACR>300mg/g; N=21) as well as 18 low-eGFR (eGFR<60ml/min) and 32 high-eGFR (eGFR>60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression. The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR-21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR-29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement. Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.


Selenium, selenoproteins and selenometabolites in mothers and babies at the time of birth.
The deficiency of Se, an essential micronutrient, has been implicated in adverse pregnancy outcomes. Our study was designed to determine total serum Se, selenoproteins (extracellular glutathione peroxidase (GPx-3), selenoprotein P (SeP)), selenoalbumin (SeAlb) and selenometabolites in healthy women and their newborns at delivery. This cross-sectional study included eighty-three healthy mother-baby couples. Total Se and Se species concentrations were measured in maternal and umbilical cord sera by an in-series coupling of two-dimensional size-exclusion and affinity HPLC. Additional measurements of serum SeP concentration and of serum GPx-3 enzyme activity were carried out using ELISA. Total Se concentration was significantly higher in maternal serum than in cord serum (68·9 (sd 15·2) and 56·1 (sd 14·6) µg/l, respectively; P<0·01). There were significant correlations between selenoprotein and SeAlb concentrations in mothers and newborns, although they also showed significant differences in GPx-3 (11·2 (sd 3·7) v. 10·5 (sd 3·5) µg/l; P<0·01), SeP (42·5 (sd 9·5) v. 28·1 (sd 7·7) µg/l; P<0·01) and SeAlb (11·6 (sd 3·6) v. 14·1 (sd 4·3) µg/l; P<0·01) concentrations in maternal and cord sera, respectively. Serum GPx-3 activity and concentration were positively correlated in mothers (r 0·33; P=0·038) but not in newborns. GPx-3 activity in cord serum was significantly correlated with gestational age (r 0·44; P=0·009). SeAlb concentration was significantly higher in babies, whereas SeP and GPx-3 concentrations were significantly higher in mothers. The differences cannot be explained by simple diffusion; specific transfer mechanisms are probably involved. GPx-3 concentrations in mothers, at delivery, are related to maternal Se status, whereas the GPx-3 activity in cord serum depends on gestational age.


Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens.
The etiology of bacteremia in febrile neutropenic patients in the past few decades has shifted from gram-negative to gram-positive organisms. Potential reasons include the use of indwelling catheters, local environmental conditions, and the administration of specific antibiotic agents, especially as prophylaxis. Other factors may emerge from new studies, such as the categorization of febrile neutropenic patients into groups at low risk and at high risk of developing serious complications, continuing changes in resistance in the community, the use of antibiotic-coated catheters, and future changes in cytotoxic chemotherapy or antineoplastic therapy. In addition, there has been a drift in susceptibility patterns, with resistance issues seen in the general population of hospitalized patients now emerging in febrile neutropenic patients, as well as some issues specific to these patients. These changes affect empirical therapy as it was practiced a decade ago. Among the most commonly used agents, cefepime and carbapenems continue to show the highest rates of in vitro susceptibility, providing coverage against most gram-positive and gram-negative organisms and reducing the need for glycopeptides. Older agents continue to show degradation of their effectiveness. Among Pseudomonas aeruginosa strains, susceptibility to all agents continues to decline.


[Rate of G gamma and A gamma chains in Dong ethnic newborns and gene mapping of a case with high G gamma value].
The G gamma to A gamma ratio of fetal hemoglobin in 120 cord blood samples of Dong ethnic newborns distributed over the Dong Autonomous Regions in Guangxi and Hunan provinces were determined with the method of polyacrylamide gel electrophoresis. The result showed that a case has the high G gamma value of 81.4% while 119 babies have the normal G gamma values of 56 to 76% (69.4 +/- 3.1%). The high G gamma case was identified as G gamma-AG gamma-A gamma/G gamma-A gamma genotype.


Antibiotic Prophylaxis against Surgical Site Infection after Open Hernia Surgery: A Systematic Review and Meta-Analysis.
The role of antibiotic prophylaxis (AP) in the prevention of surgical site infection (SSI) after hernia repair is debated. We conducted this systematic review and meta-analysis to assess the evidence on the value of prophylactic antibiotics in reducing the risks of SSI after open hernia surgery. We ran an online and manual search to identify relevant randomized controlled trials that compared prophylactic antibiotics to nonantibiotic controls in patients undergoing open surgical hernia repair. Data on SSI risk were extracted and pooled as risk ratios (RRs) with 95% confidence intervals (95% CIs), using RevMan software. We further used the Cochrane risk of bias tool and GRADE assessment to evaluate the quality of generated evidence. Twenty-nine studies (N = 8,616 patients) were included in the current analysis. Antibiotic prophylaxis reduced the risk of SSI in open hernia repair patients (RR = 0.65, 95% CI = 0.53, 0.79). Subgroup analysis showed a significant benefit for antibiotics in mesh repair patients (RR = 0.60, 95% CI = 0.48, 0.76) yet no significant difference in SSI risk after herniorrhaphy (RR = 0.86, 95% CI = 0.54, 1.36). In addition, AP was associated with a significant reduction in superficial SSI risk (RR = 0.56, 95% CI = 0.43, 0.72) but not deep SSI (RR = 0.70, 95% CI = 0.30, 1.62). Further analysis showed a significant reduction in SSI risk with amoxicillin/clavulanic acid and cefazolin but not with cefuroxime. The present meta-analysis suggests that AP is beneficial prior to open mesh hernia repair. However, the quality of evidence was low, and further well-designed trials are needed.


Three-Year Outcomes of Orbital Atherectomy for the Endovascular Treatment of Infrainguinal Claudication or Chronic Limb-Threatening Ischemia.
Purpose: To investigate the outcomes of orbital atherectomy (OA) for the treatment of patients with peripheral artery disease (PAD) manifesting as claudication or chronic limb-threatening ischemia (CLTI). Materials and Methods: The database from the LIBERTY study (ClinicalTrials.gov identifier NCT01855412) was interrogated to identify 503 PAD patients treated with any commercially available endovascular devices and adjunctive OA for 617 femoropopliteal and/or infrapopliteal lesions. Cox regression analyses were employed to examine the association between baseline Rutherford category (RC) stratified as RC 2-3 (n=214), RC 4-5 (n=233), or RC 6 (n=56) and all-cause mortality, target vessel revascularization (TVR), major amputation, major adverse event (MAE), and major amputation/death at up to 3 years of follow-up. The mean lesion lengths were 78.7±73.7, 131.4±119.0, and 95.2±83.9 mm, respectively, for the 3 groups. Results: After OA, balloon angioplasty was used in >98% of cases, with bailout stenting necessary in 2.0%, 2.8%, and 0% of the RC groups, respectively. A small proportion (10.8%) of patients developed angiographic complications, without differences based on presentation. During the 3-year follow-up, claudicants were at lower risk for MAE, death, and major amputation/death than patients with CLTI. The 3-year Kaplan-Meier survival estimates were 84.6% for the RC 2-3 group, 76.2% for the RC 4-5 group, and 63.7% for the RC 6 group. The 3-year freedom from major amputation was estimated as 100%, 95.3%, and 88.6%, respectively. Among CLTI patients only, the RC at baseline was correlated with the combined outcome of major amputation/death, whereas RC classification did not affect TVR, MAE, major amputation, or death rates. Conclusion: Peripheral artery angioplasty with adjunctive OA in patients with CLTI or claudication is safe and associated with low major amputation rates after 3 years of follow-up. These results demonstrate the utility of OA for patients across the spectrum of PAD.


Distal femoral cortical irregularity in a 13-year old boy. A case report.
Distal femoral cortical irregularity (DFCI) is a benign entity presenting with either an irregular appearance or a focal radiolucency within the posterior cortex of the distal femur. Atypical cases should be differentiated from malignant lesions. The typical location of the lesion at the attachment of the head of the medial gastrocnemius muscle can be visualised using different imaging techniques. We report a case of a DFCI in a 13-year old boy. The diagnosis was based on CT-imaging. Two years later, no radiological abnormalities could be observed. A review of the literature is presented.


Neuronal damage and cognitive impairment associated with hypoglycemia: An integrated view.
The aim of the present review is to offer a current perspective about the consequences of hypoglycemia and its impact on the diabetic disorder due to the increasing incidence of diabetes around the world. The main consequence of insulin treatment in type 1 diabetic patients is the occurrence of repetitive periods of hypoglycemia and even episodes of severe hypoglycemia leading to coma. In the latter, selective neuronal death is observed in brain vulnerable regions both in humans and animal models, such as the cortex and the hippocampus. Cognitive damage subsequent to hypoglycemic coma has been associated with neuronal death in the hippocampus. The mechanisms implicated in selective damage are not completely understood but many factors have been identified including excitotoxicity, oxidative stress, zinc release, PARP-1 activation and mitochondrial dysfunction. Importantly, the diabetic condition aggravates neuronal damage and cognitive failure induced by hypoglycemia. In the absence of coma prolonged and severe hypoglycemia leads to increased oxidative stress and discrete neuronal death mainly in the cerebral cortex. The mechanisms responsible for cell damage in this condition are still unknown. Recurrent moderate hypoglycemia is far more common in diabetic patients than severe hypoglycemia and currently important efforts are being done in order to elucidate the relationship between cognitive deficits and recurrent hypoglycemia in diabetics. Human studies suggest impaired performance mainly in memory and attention tasks in healthy and diabetic individuals under the hypoglycemic condition. Only scarce neuronal death has been observed under moderate repetitive hypoglycemia but studies suggest that impaired hippocampal synaptic function might be one of the causes of cognitive failure. Recent studies have also implicated altered mitochondrial function and mitochondrial oxidative stress.


Denbinobin, a phenanthrene from Dendrobium nobile, impairs prostate cancer migration by inhibiting Rac1 activity.
Prostate cancer is the most prevalent type of cancer in the United States. The most common site of prostate cancer metastasis is bone. CXCL12 is preferentially expressed in bone and is targeted by prostate cancer cells, which over-express the receptor for CXCL12, CXCR4. In response to CXCL12 stimulation, Rac1, a GTPase, along with its effectors, regulates actin polymerization to form lamellipodia, which is a critical event for cell migration. Cortactin, an actin-binding protein, is recruited to the lamellipodia and is phosphorylated at tyrosine residues. The phosphorylated cortactin is also involved in cell migration. The inhibition of Rac1 activity using a dominant negative Rac1 impairs lamellipodial protrusion as well as cortactin translocation and cortactin phosphorylation. Denbinobin, a substance extracted from Dendrobium nobile, has anticancer effects in many cancer cell lines. Whether denbinobin can inhibit prostate cancer cell migration is not clear. Here, we report that denbinobin inhibited Rac1 activity. The inhibition of Rac1 activity prevented lamellipodial formation. Cortactin phosphorylation and translocation to the lamellipodia were also impaired, and PC3 cells were unable to migrate. These results indicate that denbinobin prevents CXCL12-induced PC3 cell migration by inhibiting Rac1 activity.


Nurses among EU workers lobbying for right to remain in the UK.
Nurses, social workers and teaching assistants were among European Union (EU) workers lobbying MPs last week over their right to remain in the UK.


T cell homing to tumors detected by 3D-coordinated positron emission tomography and magnetic resonance imaging.
A general hindrance to progress in adoptive cellular therapy is the lack of detailed knowledge of the fate of transferred cells in the body of the recipient. In this study, we present a novel technique for tracking of 124I-labeled cells in situ, which combines the high spatial resolution of magnetic resonance imaging with the high sensitivity and spatial accuracy of positron emission tomography. We have used this technique, together with determination of tissue radioactivity, flow cytometry, and microscopy, to characterize and quantitate the specific accumulation of transferred CD8+ T cells in tumor tissue in a mouse model. Transgenic CD8+ T cells, specific for the ovalbumin peptide SIINFEKL, were adoptively transferred to recipients carrying a subcutaneous tumor of the ovalbumin-expressing malignant melanoma cell line B16-OVA. The number of SIINFEKL-specific CD8+ cells in the tumor tissue was determined by flow cytometry each day for 8 consecutive days after adoptive transfer. From low levels 1 day after injection, their number gradually increased until day 5 when an average of 3.3x10(6) SIINFEKL-specific cells per gram tumor tissue was found. By applying the combined positron emission tomography/magnetic resonance imaging technique we were able to determine the position of the transferred, 124I-labeled SIINFEKL-specific T cells in 3 dimensions in recipient mice, and could demonstrate a highly significant accumulation of the 124I label in and around the subcutaneous B16-OVA tumors compared with normal tissue. Accumulation of 124I was significantly higher in B16-OVA than in B16 tumors not expressing the OVA antigen.


Specific active lung cancer immunotherapy. Immune correlates of clinical responses and an update of immunotherapy trials evaluations.
The mechanisms of action of the specific active immunotherapy of solid tumors have not been defined. In an attempt to characterize some of these mechanisms, we report controlled studies of humoral immune responses and cell-mediated immune (CMI) responses in lung cancer patients with Stage I and Stage II adenocarcinoma and squamous cell cancer receiving pure tumor-associated antigen (TAA) specific active immunotherapy or combination immunochemotherapy. At 5 to 6 months postimmunotherapy, the humoral immune response measurements are predictive of response to therapy/survival in early lung cancer patients, permitting decisions as to whether to continue therapy. Patients with adenocarcinoma respond to combination chemoimmunotherapy by showing stronger or earlier responses to tests of immunity. Cell-mediated immunity to TAA at 17 to 24 months was far greater in patients receiving immunotherapy or immunochemotherapy compared with control patients, and also correlated with early humoral immune response and with 5-year survival. Here we report a further subset analysis of Stage I and Stage II lung cancer patients in a successful Phase III US specific active immunotherapy trial as substantiating the experience with Stage I patients in a successful Phase II Canadian trial. We analyze failures and suggest additional therapies, especially a chemoimmunotherapy trial indicated by our analyses of humorocellular immune variables reported here.


Solitary fibrous tumor of the orbit: morphological, cytogenetic and molecular features.
Solitary fibrous tumor (SFT), a benign neoplasm arising in mesenchymal structures, was initially described in the pleura but subsequently has also been documented in other locations. It is uncommon in the orbit, where it closely resembles other benign spindle-shaped mesenchymal tumors of this area such as schwannoma, meningioma or hemangiopericytoma. We present a case of orbital SFT in a 34-year-old woman. The radiological study showed the presence of an enhanced uptake lesion measuring 2 cm in major diameter. The histopathological evaluation revealed alternating cellular and hypocellular areas with spindle-shaped cells. The cellular organization displayed a broad variety of irregular morphological patterns. The neoplastic cells were intensely positive for CD34 and vimentin, while S100, epithelial membrane antigen (EMA), Caldesmon, Calretinin and WT-1 proved negative. The pericellular matrix exhibited strong positivity for CD44 and collagen IV. Scarce mitotic figures, a Ki-67 nuclear labeling index of <5%, and focal expression of p53 were also observed. Measurement of DNA content revealed a DNA index of 1, indicating a diploid peak in 95% of the tumor cells. A normal 46,XX karyotype was present. No TP53 (exons 5-8) mutations or MDM2 and CDK4 amplifications were observed. No p14(ARF), p15(INK4B) and p16(INK4A) deletions or hypermethylation were observed in this benign tumor. Following surgical resection and radiotherapy, the patient showed no tumor relapse after one year of follow-up.


Effects of converting-enzyme inhibitors on the renin-angiotensin-aldosterone, bradykinin, and arachidonic acid-prostaglandin systems: correlation of chemical structure and biologic activity.
The renin-angiotensin-aldosterone system plays an integral role in the control of BP and is mediated by enzymatic transformation of substances in the renin-angiotensin cascade. Inhibitors of various reactions in this cascade have been shown experimentally to reduce elevated BP. The first such compound to become available for clinical use was the angiotensin-converting enzyme inhibitor captopril. Captopril reduces BP, with the expected decrease in plasma angiotensin II concentration and increases in renin and angiotensin I levels, but there is also evidence for a non-renin-dependent mechanism of action. In particular, according to cell culture data, captopril stimulates an increase in the synthesis of vasodilatory prostaglandins. Because enalapril, another angiotensin-converting-enzyme inhibitor, does not augment in vitro synthesis of prostaglandins, this effect may be unique to the chemical structure of captopril rather than inherent to all such inhibitors. Studies using animal models of hypertension support this hypothesis. Captopril may also influence prostaglandin synthesis by reducing inactivation of bradykinin.


Analysis of multiple internal reflections in a parallel aligned liquid crystal on silicon SLM.
Multiple internal reflection effects on the optical modulation of a commercial reflective parallel-aligned liquid-crystal on silicon (PAL-LCoS) spatial light modulator (SLM) are analyzed. The display is illuminated with different wavelengths and different angles of incidence. Non-negligible Fabry-Perot (FP) effect is observed due to the sandwiched LC layer structure. A simplified physical model that quantitatively accounts for the observed phenomena is proposed. It is shown how the expected pure phase modulation response is substantially modified in the following aspects: 1) a coupled amplitude modulation, 2) a non-linear behavior of the phase modulation, 3) some amount of unmodulated light, and 4) a reduction of the effective phase modulation as the angle of incidence increases. Finally, it is shown that multiple reflections can be useful since the effect of a displayed diffraction grating is doubled on a beam that is reflected twice through the LC layer, thus rendering gratings with doubled phase modulation depth.


Tumor necrosis factor (cachectin) mediates induction of cachexia by cord factor from mycobacteria.
The mechanism by which cord factor (CF), a toxic glycolipid from mycobacteria, induces cachexia was studied in BALB/c mice. Body weight was markedly reduced 48 h after CF administration; the animals became severely wasted and exhibited hypertriglyceridemia, hypoglycemia, and high levels of tumor necrosis factor (TNF) in plasma. After CF administration, a transferable factor which caused cachexia and hypertriglyceridemia in recipient mice was detected in the blood. Dexamethasone partially inhibited the cachexia-inducing action of CF. Conditioned medium from adherent peritoneal cell cultures incubated with CF produced the same wasting symptoms when inoculated intravenously into mice. These studies also demonstrated that adherent peritoneal cells produced a humoral factor in response to CF which was related to CF-induced cachexia. Antiserum to recombinant TNF-alpha prevented the cachectin action in passive-transfer experiments. Our findings indicate that cachectin (TNF) plays a role as a central mediator of the wasting induced by CF.


The effects of home exercise program on limb-girdle disease: a cohort study.
This study aims to demonstrate the effectiveness of rehabilitation in patients with limb-girdle disease, who were given a home exercise program and called for follow-up in certain periods by observing the functional areas of the shoulder and pelvic groups every six months. Suitable statistical methods were conducted. Descriptive findings and continuous variables regarding the patients were presented. As a result of the analyses, no statistically significant difference was found only in pre-treatment and post-treatment wrist strength and trunk extension variables, but a statistically significant difference was found between the pre-treatment and post-treatment scores of all other types of strength. Significant differences were found between the pre-treatment and post-treatment cervical flexion strength in terms of general weakness and inability to walk, joint limitation and walking status. It is believed that the rehabilitation method to be applied to patients with limb-girdle muscular dystrophy (LGMD) detected in the early period will provide effective results and may form the basis for referring them to physicians and health professionals. It has been concluded that rehabilitation will help them lead a comfortable life.


Theorizing is for everybody: Advancing the process of theorizing in implementation science.
There has been a call to shift from treating theories as static products to engaging in a process of theorizing that develops, modifies, and advances implementation theory through the accumulation of knowledge. Stimulating theoretical advances is necessary to improve our understanding of the causal processes that influence implementation and to enhance the value of existing theory. We argue that a primary reason that existing theory has lacked iteration and evolution is that the process for theorizing is obscure and daunting. We present recommendations for advancing the process of theorizing in implementation science to draw more people in the process of developing and advancing theory.


Black soybean seed coat polyphenols prevent AAPH-induced oxidative DNA-damage in HepG2 cells.
Black soybean seed coat extract (BE), which contains abundant polyphenols such as procyanidins, cyanidin 3-glucoside, (+)-catechin, and (-)-epicatechin, has been reported on health beneficial functions such as antioxidant activity, anti-inflammatory, anti-obesity, and anti-diabetic activities. In this study, we investigated that prevention of BE and its polyphenols on 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH)-induced oxidative DNA damage, and found that these polyphenols inhibited AAPH-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for oxidative DNA damage in HepG2 cells. Under the same conditions, these polyphenols also inhibited AAPH-induced accumulation of reactive oxygen species (ROS) in the cells. Inhibition of ROS accumulation was observed in both cytosol and nucleus. It was confirmed that these polyphenols inhibited formation of AAPH radical using oxygen radical absorbance capacity assay under the cell-free conditions. These results indicate that polyphenols in BE inhibit free radical-induced oxidative DNA damages by their potent antioxidant activity. Thus, BE is an effective food material for prevention of oxidative stress and oxidative DNA damages.


Metalinguistic judgments in normal aging and Alzheimer's disease.
This study compared sentence acceptability judgments from young and healthy older adults and older adults with dementia due to probable Alzheimer's disease. Two types of sentences were contrasted: one type involved contrasts among verb alternations in which semantic distinctions between verbs regulate the acceptability of phrase structure variations; the second type involved contrasts among directional transformations in which constraints on the movement of noun phrases determine the linear order of main and embedded clauses. The primary findings were that metalinguistic judgments by healthy older adults as well as those with probable Alzheimer's reflected processing demands on working memory. In addition, metalinguistic judgments by adults with probable Alzheimer's reflected the breakdown of semantic information about verbs.


Genotype-phenotype analysis in HbS-beta-thalassemia.
Genotypes and phenotypes were studied in 31 Turkish HbS-beta-thalassemia patients. In 19 patients the beta-thalassemia mutations were beta+ and in 12 the beta 0 phenotype. The IVSI-110 mutation was found in 45% of the patients. IVSI-1, beta 39, IVSII-1 and FSC8 are the genotypes associated with beta 0-thalassemia. Hematological data were evaluated at the time of diagnosis and 4 years after diagnosis. The mean HbF value was 13 +/- 7.8% at diagnosis and 9.7 +/- 7.8% 4 years later. A significant negative correlation was observed between the age of the patients and the HbF value (p < 0.05). No statistically significant differences were observed between the mean of hematological parameters in beta(+)- and beta 0-thalassemia patients except for the mean HbF value which were 10.7 +/- 6.9 and 15.9 +/- 7.7% in beta(+)- and beta 0-thalassemia, respectively (p < 0.05). The study indicated that beta-thalassemia mutations in trans to the HbS mutation do not exert any beneficial effect on the manifestation of the disease.


Varieties of deception and distrust: moral dilemmas in the ethnography of psychiatry.
This article considers the ethical guidelines concerning autonomy, negotiated consent and transparency in relation to an ethnography of psychiatry. It suggests that the complexities and unequal power distribution of the psychiatric consultation make these guidelines difficult to apply. Rather an attempt is made to develop an ethics of patient acknowledgement even where this presents ethical misgivings vis-à-vis psychiatrists. I argue for the importance of ethnography rather than the instantiation of abstract principles to the development of an ethical perspective.


The efficacy of letrozole supplementation for medical abortion: a meta-analysis of randomized controlled trials.
The efficacy of letrozole supplementation for medical abortion remains controversial. We conduct a systematic review and meta-analysis to explore the influence of letrozole supplementation for medical abortion. We searched PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through October 2018 for randomized controlled trials (RCTs) assessing the effect of letrozole supplementation for medical abortion. This meta-analysis is performed using the random-effect model. Six RCTs involving 555 patients are included in the meta-analysis. Overall, compared with control group for pregnant women, letrozole supplementation shows significantly increased complete abortion (RR = 1.38; 95% CI = 1.07-1.78; p = .01), and decreased estradiol (std. MD = -2.86; 95% CI = -4.45 to -1.27; p = .0004), but has no remarkable effect on induction-abortion time (std. MD = -1.03; 95% CI = -2.99-0.93; p = .30), progesterone (std. MD = 0.02; 95% CI = -0.30-0.34; p = .89), vaginal hemorrhage (std. MD = 1.84; 95% CI = 0.05-70.90; p = .74), nausea and vomiting (std. MD = 073; 95% CI = 0.44-1.21; p = .22). Letrozole supplementation provides benefits to medical abortion in pregnant women.


Ruptured ovarian cyst as a cause of ascites in a newborn infant.
Symptomatic ovarian cysts in newborn are rare. In a recent series of cases of congenital ascites ( Griscom et al 1977) only one case out of 27 was caused by an ovarian cyst. We describe a case in which congenital ascites was caused by a ruptured corpus luteum ovarian cyst.


Efficacy of three IV non-opioid-analgesics on opioid consumption for postoperative pain relief after total thyroidectomy: a randomised, double-blind trial.
In a randomized, double-blind trial, the synergistic action of intravenous parecoxib, metamizol or paracetamol on postoperative piritramide consumption was compared in patients recovering from total thyroidectomy during the first 24 h while evaluating pain intensity and patient satisfaction. 120 patients were randomly allocated to four patient groups treated with normal saline and/or one of non-opioid analgesics (parecoxib 40 mg twice daily, metamizol 1 g three times daily, paracetamol 1 g three times daily) in addition to piritramide using the PCA pump. Beginning in the recovery room (PACU), patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience and patient satisfaction while piritramide consumption was recorded. Upon arrival in the PACU piritramide consumption was high and decreased thereafter significantly in all groups (P < 0.05). There were no significant differences between groups in incremental and cumulative piritramide consumption during the investigation. Also, VAS scores were high upon arrival in the PACU and dropped in all groups continuously after surgery: At 2 h and 4 h after surgery they were significantly lower in parecoxib group compared with NaCl (P < 0.01). For overall patient satisfaction, no significant differences were observed. Pain relief scores at 24 h were significantly higher in parecoxib group as compared to metamizol and paracetamol (P < 0.01). Mild PONV was observed frequently in all groups and was treated with metoclopramide. There is no clear-cut difference between the non-opioid drugs used, even though parecoxib seems to be superior in regard to VAS scores and piritramide consumption. However, the clinical significance is debatable.


Skeletal muscle mitochondrial network dynamics in metabolic disorders and aging.
With global demographics trending towards an aging population, the numbers of individuals with an age-associated loss of independence is increasing. A key contributing factor is loss of skeletal muscle mitochondrial, metabolic, and contractile function. Recent advances in imaging technologies have demonstrated the importance of mitochondrial morphology and dynamics in the pathogenesis of disease. In this review, we examine the evidence for altered mitochondrial dynamics as a mechanism in age and obesity-associated loss of skeletal muscle function, with a particular focus on the available human data. We highlight some of the areas where more data are needed to identify the specific mechanisms connecting mitochondrial morphology and skeletal muscle dysfunction.


A Comparison Between the Effect of Cuminum Cyminum and Vitamin E on the Level of Leptin, Paraoxonase 1, HbA1c and Oxidized LDL in Diabetic Patients.
Diabetes is one of the most common metabolic diseases in the world. Vitamin E reduces protein glycation and improves insulin sensitivity, while cumin is effective in remission of diabetes. Therefore this study was designed to evaluate the effects of vitamin E and cumin essential oil, on the blood level of leptin,glycosylated hemoglobin (HbA1C) and also on lipid profile in diabetic patients.In this double blind clinical trial, 95 diabetic patients were selected and randomly dividedinto three groups.The first group received cumin essential oil in capsule form. The second group received Vitamin E, and the third group was used ascontrol receiving oral gelatin capsules as placebo for three months period.Blood glucose, lipid profile, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), leptin, HbA1c, oxidized LDL (oxLDL), and paraoxonase1 activity were measured. The results showed reduction in oxLDL and significant increase in paraoxonase 1 in Vitamin E group by the end of the third month period (P<0.05). Cumin group showed decrease in blood glucose, HbA1C, triglyceride, leptin and ox-LDL. ApoA1 and paraoxonase1 were also increased by cumin treatment (P<0.05).Diabetic complications may have been reduced by intake of Vitamin E and cumin essential oil. Cumin in comparison with vitamin E has broader impact and it is more beneficial in terms of ability to reduce the diabetic index.


Use of gene probes to assess the impact and effectiveness of aerobic in situ bioremediation of TCE.
Gene probe hybridization was used to determine distribution and expression of co-metabolic genes at a contaminated site as it underwent in situ methanotrophic bioremediation of trichloroethylene (TCE). The bioremediation strategies tested included a series of air, air:methane, and air:methane:nutrient pulses of the test plot using horizontal injection wells. During the test period, the levels of TCE reduced drastically in almost all test samples. Sediment core samples (n=367) taken from 0 m (surface)-43 m depth were probed for gene coding for methanotrophic soluble methane monooxygenase (sMMO) and heterotrophic toluene dioxygenase (TOD), which are known to co-metabolize TCE. The same sediment samples were also probed for genes coding for methanol dehydrogenase (MDH) (catalyzing the oxidation of methanol to formaldehyde) to assess specifically changes in methylotrophic bacterial populations in the site. Gene hybridization results showed that the frequency of detection of sMMO genes were stimulated approximately 250% following 1% methane:air (v/v) injection. Subsequent injection of 4% methane:air (v/v) resulted in an 85% decline probably due to nutrient limitations, since addition of nutrients (gaseous nitrogen and phosphorus) thereafter caused an increase in the frequency of detection of sMMO genes. Detection of TOD genes declined during the process, and eventually they were non-detectable by the final treatment, suggesting that methanotrophs displaced the TOD gene containing heterotrophs. Active transcription of sMMO and TOD was evidenced by hybridization to mRNA. These analyses combined with results showing the concomitant decline in TCE concentrations, increases in chloride concentration and increases in methanotroph viable counts, provide multiple lines of evidence that TCE remediation was caused specifically by methanotrophs. Our results suggest that sMMO genes are responsible for most, if not all, of the observed biodegradation of TCE. This study demonstrates that the use of nucleic acid analytical methods provided a gene specific assessment of the effects of in situ treatment technologies.


Surgical treatment of ovarian vein thrombosis.
Ovarian vein thrombosis is a rare but serious condition that may cause sepsis in the postpartum patient or may be associated with thrombosis of the inferior vena cava or renal vein. A 30-year-old woman presented 2 weeks postpartum with sudden onset of dyspnea and rightsided pleuritic chest pain. She was diagnosed with a large pulmonary embolus and thrombosis of the right ovarian vein. After failure of percutaneous embolization of the right ovarian vein, the patient underwent open surgical excision of the right ovarian vein. The management of ovarian vein thrombosis may involve systemic anticoagulation, antibiotics, thrombolysis, open surgical treatment, or a combination of these.


KEG1/YFR042w encodes a novel Kre6-binding endoplasmic reticulum membrane protein responsible for beta-1,6-glucan synthesis in Saccharomyces cerevisiae.
KEG1/YFR042w of Saccharomyces cerevisiae is an essential gene that encodes a 200-amino acid polypeptide with four predicted transmembrane domains. The green fluorescent protein- or Myc(6)-tagged Keg1 protein showed the typical characteristics of an integral membrane protein and was found in the endoplasmic reticulum by fluorescence imaging. Immunoprecipitation from the Triton X-100-solubilized cell lysate revealed that Keg1 binds to Kre6, which has been known to participate in beta-1,6-glucan synthesis. To analyze the essential function of Keg1 in more detail, we constructed temperature-sensitive mutant alleles by error-prone polymerase chain reaction. The keg1-1 mutant cells showed a common phenotype with Deltakre6 mutant including hypersensitivity to Calcofluor white, reduced sensitivity to the K1 killer toxin, and reduced content of beta-1,6-glucan in the cell wall. These results suggest that Keg1 and Kre6 have a cooperative role in beta-1,6-glucan synthesis in S. cerevisiae.


Differential response to stress in Ostrea lurida as measured by gene expression.
Olympia oysters are the only oyster native to the west coast of North America. The population within Puget Sound, WA has been decreasing significantly since the early 1900's. Current restoration efforts are focused on supplementing local populations with hatchery bred oysters. A recent study by Heare et al. (2017) has shown differences in stress response in oysters from different locations in Puget Sound however, nothing is known about the underlying mechanisms associated with these observed differences. In this study, expression of genes associated with growth, immune function, and gene regulatory activity in oysters from Oyster Bay, Dabob Bay, and Fidalgo Bay were characterized following temperature and mechanical stress. We found that heat stress and mechanical stress significantly changed expression in molecular regulatory activity and immune response, respectively. We also found that oysters from Oyster Bay had the most dramatic response to stress at the gene expression level. These data provide important baseline information on the physiological response of Ostrea lurida to stress and provide clues to underlying performance differences in the three populations examined.


Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus.
Innate lymphoid cells (ILCs) are important regulators in various immune responses. The current paradigm states that all newly made ILCs originate from common lymphoid progenitors in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Unexpectedly, we found that ectopically expressing Id1 or deleting two E protein genes in the thymus drastically increased ILC2 counts in the thymus and other organs where ILC2 normally reside. Further evidence suggests a thymic origin of these mutant ILC2s. The mutant mice exhibit augmented spontaneous infiltration of eosinophils and heightened responses to papain in the lung and increased ability to expulse the helminth parasite, Nippostrongylus brasiliensis These results prompt the questions of whether the thymus naturally has the capacity to produce ILC2s and whether E proteins restrain such a potential. The abundance of ILC2s in Id1 transgenic mice also offers a unique opportunity for testing the biological functions of ILC2s.


Insertion of a MalE beta-galactosidase fusion protein into the envelope of Escherichia coli disrupts biogenesis of outer membrane proteins and processing of inner membrane proteins.
The synthesis of a membrane-bound MalE beta-galactosidase hybrid protein, when induced by growth of Escherichia coli on maltose, leads to inhibition of cell division and eventually a reduced rate of mass increase. In addition, the relative rate of synthesis of outer membrane proteins, but not that of inner membrane proteins, was reduced by about 50%. Kinetic experiments demonstrated that this reduction coincided with the period of maximum synthesis of the hybrid protein (and another maltose-inducible protein, LamB). The accumulation of this abnormal protein in the envelope therefore appeared specifically to inhibit the synthesis, the assembly of outer membrane proteins, or both, indicating that the hybrid protein blocks some export site or causes the sequestration of some limiting factor(s) involved in the export process. Since the MalE protein is normally located in the periplasm, the results also suggest that the synthesis of periplasmic and outer membrane proteins may involve some steps in common. The reduced rate of synthesis of outer membrane proteins was also accompanied by the accumulation in the envelope of at least one outer membrane protein and at least two inner membrane proteins as higher-molecular-weight forms, indicating that processing (removal of the N-terminal signal sequence) was also disrupted by the presence of the hybrid protein. These results may indicate that the assembly of these membrane proteins is blocked at a relatively late step rather than at the level of primary recognition of some site by the signal sequence. In addition, the results suggest that some step common to the biogenesis of quite different kinds of envelope protein is blocked by the presence of the hybrid protein.


Influenza virus protein PB1-F2 inhibits the induction of type I interferon by binding to MAVS and decreasing mitochondrial membrane potential.
PB1-F2 is a small, 87- to 90-amino-acid-long protein encoded by the +1 alternate open reading frame of the PB1 gene of most influenza A virus strains. It has been shown to contribute to viral pathogenicity in a host- and strain-dependent manner, and we have previously discovered that a serine at position 66 (66S) in the PB1-F2 protein increases virulence of the 1918 and H5N1 pandemic viruses. Recently, we have shown that PB1-F2 inhibits the induction of type I interferon (IFN) at the level of the MAVS adaptor protein. However, the molecular mechanism for the IFN antagonist function of PB1-F2 has remained unclear. In the present study, we demonstrated that the C-terminal portion of the PB1-F2 protein binds to MAVS in a region that contains the transmembrane domain. Strikingly, PB1-F2 66S was observed to bind to MAVS more efficiently than PB1-F2 66N. We also tested the effect of PB1-F2 on the IFN antagonist functions of the polymerase proteins PB1, PB2, and PA and observed enhanced IFN inhibition by the PB1 and PB2 proteins in combination with PB1-F2 but not by the PA protein. Using a flow cytometry-based assay, we demonstrate that the PB1-F2 protein inhibits MAVS-mediated IFN synthesis by decreasing the mitochondrial membrane potential (MMP). Interestingly, PB1-F2 66S affected the MMP more efficiently than wild-type PB1-F2. In summary, the results of our study identify the molecular mechanism by which the influenza virus PB1-F2 N66S protein increases virulence.


Effect of endocrine disrupting chemicals on lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by mouse macrophages.
Little is known about the development of infectious diseases during exposure to endocrine disrupting chemicals (EDCs), although several studies have reported on the effect of EDCs on the immune function of the human body. To assess the effect of EDCs on the development of infectious disease, we investigated the effect of eighteen possible EDCs on mouse macrophage production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in response to bacterial endotoxin in vitro and ex vivo. Of chemicals we examined, simazine, nitrofen, and benzyl butyl phthalate inhibited lipopolysaccharide (LPS)-induced TNF-alpha production by mouse macrophage cell line RAW 264 in vitro. Carbaryl, alachlor, nonylphenol, octylphenol, tributyltin, and triphenyltin inhibited LPS-induced NO production in vitro, whereas 2,4-dichlorophenoxy acetic acid and bisphenol A enhanced its production. Zineb and alachlor, on the other hand, enhanced LPS-induced TNF-alpha production by mouse peritoneal macrophages ex vivo, while alachlor inhibited LPS/interferon-gamma-induced NO production ex vivo. These results indicate that some EDCs exert modulatory activity on endotoxin-induced macrophage activation either positively or negatively, suggesting that these compounds may affect the development of infectious diseases. This is the first report that systematically compared the effect of EDCs on LPS action.


Expression of foreign proteins in microorganisms.
The various alternative strategies for the expression of heterologous proteins in microorganisms are reviewed. To illustrate how these general considerations can be addressed in particular cases, the expression of chimeric human-mouse antibodies in Escherichia coli and the production of thaumatin, an intensely sweet plant protein, in yeast, are described.


Effects of MK-801 and ethanol combinations on memory consolidation in CD1 mice: involvement of GABAergic mechanisms.
In the present research the effect of the noncompetitive N-methyl-d-aspartate receptor antagonist MK-801 and ethanol combinations on memory consolidation and the involvement of GABAergic mechanisms in this effect were investigated in CD1 mice injected intraperitoneally with the drugs immediately or 120 min after training in a one-trial inhibitory avoidance apparatus and tested for retention 24 h later. The results showed that (a) the retention performances of mice were impaired in a dose-dependent manner by immediate posttraining MK-801 (0.2 and 0.3, but not 0.1 mg/kg) and ethanol (1 and 2, but not 0.5 g/kg) administrations; (b) an otherwise ineffective dose of MK-801 (0.1 mg/kg) enhanced the deleterious effect exerted by ethanol (1 and 2 g/kg); (c) an otherwise ineffective dose of muscimol (0.5 mg/kg) enhanced, while otherwise ineffective doses of picrotoxin (0.25 mg/kg) or bicuculline (0.1 mg/kg) antagonized, this effect; and (d) no effect was observed when the treatments were carried out 120 min after training, suggesting that the effects observed following immediate posttraining administrations were due to the influence on the consolidation of memory. From these experiments it is evident that (a) MK-801 enhances ethanol's effects on memory consolidation and (b) GABAergic mechanisms are involved in this effect.


The action of mimetic peptides on connexins protects fibroblasts from the negative effects of ischemia reperfusion.
Connexins have been proposed as a target for therapeutic treatment of a variety of conditions. The main approaches have been by antisense or small peptides specific against connexins. Some of these peptides enhance communication while others interfere with connexin binding partners or bind to the intracellular and extracellular loops of connexins. Here, we explored the mechanism of action of a connexin mimetic peptide by evaluating its effect on gap junction channels, connexin protein levels and hemichannel activity in fibroblast cells under normal conditions and following ischemia reperfusion injury which elevates Cx43 levels, increases hemichannel activity and causes cell death. Our results showed that the effects of the mimetic peptide were concentration-dependent. High concentrations (100-300 μM) significantly reduced Cx43 protein levels and GJIC within 2 h, while these effects did not appear until 6 h when using lower concentrations (10-30 μM). Cell death can be reduced when hemichannel opening and GJIC were minimised.


Urine production and bladder function in fetuses with open spina bifida.
Hourly fetal urine production rate (HFUPR) and bladder filling and voiding were determined by real-time ultrasonography in 13 fetuses with open spina bifida (OSB) and compared with those of 101 normal fetuses from uncomplicated pregnancies at 16-40 weeks gestation. In normal pregnancy, the fetal bladder volume increases linearly with time and then decreases rapidly with micturition. The mean cycle length does not change significantly with gestation but both the mean bladder volume and HFUPR increase. In fetuses with OSB, ultrasonographic examination has demonstrated deviations from normal in both bladder filling and bladder emptying.


Influence of cerebral lesion volume and lesion distribution on event-related brain potentials in multiple sclerosis.
Neurocognitive involvement in multiple sclerosis (MS) is heterogeneous with some authors suggesting a frontal pattern in patients with predominantly frontal lesions. To assess the relationship between the distribution of lesions and two cognitive components (visual N2, auditory P3a) of the event-related brain potential (ERP) receiving contributions from frontal lobe structures, we performed a combined ERP and magnetic resonance imaging (MRI) study. Thirty-four MS patients were assigned to "low lesion volume, (LLV)"(n = 12),"high lesion volume,(HLV)"(n = 12) and"frontal lesion volume, (FLV)" (n = 10) groups according to lesion volume and distribution on T2-weighted MRI-scans of the brain. ERPs in visual and auditory classification tasks as well as neuropsychological tests were carried out in patients and control subjects (n = 15). The index for automatic feature registration, the N2 component with its mainly frontal contribution in the visual task, was significantly reduced in amplitude in the FLV and HLV groups (both p < 0.01 vs. controls). Moreover its amplitude correlated with lesion volume (r=0.64, p < 0.001). In contrast neither P3a nor P3b subcomponents with a multiple generator nature in the auditory task varied systematically with lesion volume or distribution. Total lesion volume rather than predominant lesion arrangement appears to be the most important factor in neurocognitive changes in MS. This is most consistent with the view that MS lesions lead to partial disconnections within widespread cortical networks which in turn produce a pattern of neuropsychological deficits that reflect total lesion load more than lesion distribution.


W-band millimeter-wave back-scattering system for high wavenumber turbulence measurements in LHD.
A 90 GHz W-band millimeter-wave back-scattering system is designed and installed for measuring electron scale turbulence (k⊥ρs ∼ 40). A metal lens relay antenna is used for in-vessel beam focusing, and a beam diameter of less than 40 mm is achieved in the plasma core region. This antenna can be steered at an angle of 159° ± 6°, which almost covers the plasma radius. The estimated size of the scattering volume is ∼105 mm at the edge and 135 mm at the core, respectively. A 60 m corrugated waveguide is used to achieve a low transmission loss of ∼8 dB. A heterodyne detection system for millimeter-wave circuits with probing power modulation can distinguish the scattered signal from background noise.


[Antibiotic resistance gene contamination status in air conditioning filter dust of a hospital in Wuhan City].
To understand the differences in the types and levels of antibiotic resistance genes contamination in the dust of air conditioning filters in hospital inpatient wards. Wet cotton swabs were used to collect dust samples from air conditioning filters in 19 wards of 7 departments of a third-grade general hospital in Wuhan. The 24 antibiotic resistance genes related to 6 major antibiotics were qualitatively detected by PCR, and 6 typical resistance genes were detected by real-time PCR. Sulfonamides(sulI, sulII), β-lactams(mecA, blaOXA-51, blaTEM, blaCTX-M, blaSHV, blaKPC, blaNDM-1, blaIMP, blaVIM), aminoglycosides(aac(6᾿-aph(2᾿, aacC2), macrolides(ermA, ermC, ereA), quinolones(qnrA, qnrB, qnrS), a total of five categories of 19 antibiotic resistance genes were detected in the dust of the filter. These include four carbapenem resistance genes(blaNDM-1, blaIMP, blaVIM, blaKPC). The average of absolute content(copies/g) of the six typical resistance genes from high to low was: sulI(1. 06×10~9)>sulII(1. 78×10~8)>blaNDM-1(3. 97×10~7)>aac(6᾿-aph(2᾿(3. 20×10~7)>blaTEM(1. 03×10~7)>aacC2(1. 13×10~6). Among the seven tested departments, traumatic surgery detected up to 18 resistant gene species and 6 typical genes with the highest absolute content. The absolute content of six typical genes in ICU and surgical wards was higher than medical wards. A variety of antibiotic resistance genes are detected in the dust of some hospital ward air conditioning filters, suggesting that there may be current or past pollution of resistant bacteria in the relevant environment.


Mutant analysis reveals a specific requirement for protein P30 in Mycoplasma pneumoniae gliding motility.
The cell-wall-less prokaryote Mycoplasma pneumoniae, long considered among the smallest and simplest cells capable of self-replication, has a distinct cellular polarity characterized by the presence of a differentiated terminal organelle which functions in adherence to human respiratory epithelium, gliding motility, and cell division. Characterization of hemadsorption (HA)-negative mutants has resulted in identification of several terminal organelle proteins, including P30, the loss of which results in developmental defects and decreased adherence to host cells, but their impact on M. pneumoniae gliding has not been investigated. Here we examined the contribution of P30 to gliding motility on the basis of satellite growth and cell gliding velocity and frequency. M. pneumoniae HA mutant II-3 lacking P30 was nonmotile, but HA mutant II-7 producing a truncated P30 was motile, albeit at a velocity 50-fold less than that of the wild type. HA-positive revertant II-3R producing an altered P30 was unexpectedly not fully wild type with respect to gliding. Complementation of mutant II-3 with recombinant wild-type and mutant alleles confirmed the correlation between gliding defect and loss or alteration in P30. Surprisingly, fusion of yellow fluorescent protein to the C terminus of P30 had little impact on cell gliding velocity and significantly enhanced HA. Finally, while quantitative examination of HA revealed clear distinctions among these mutant strains, gliding defects did not correlate strictly with the HA phenotype, and all strains attached to glass at wild-type levels. Taken together, these findings suggest a role for P30 in gliding motility that is distinct from its requirement in adherence.


Development of a novel PLDLA/β-TCP composite-based biodegradable anterior cervical plate and screw system.
We investigated the effectiveness and safety of a new composite-based biodegradable anterior cervical plate/screw (ACPS) system for the anterior cervical discectomy and fusion (ACDF) fixation. A biocomposite in combination with 30 wt% β-tricalcium phosphate (β-TCP; a biodegradable ceramic having osteoconductive ability) and 70 wt% poly-l/d-lactide copolymer (PLDLA; a biodegradable polymer) was developed and used in the ACPS device, comprising one plate and four screws for fixation. Based on a literature review, a clinically required period of performance maintenance was set as 16 weeks, and to verify the performance for a period of 16 weeks or more, the test was conducted for 26 weeks. Following ISO 13781:2017 testing protocols, an in vitro degradation test was performed to verify the performance and evaluate the decomposition characteristics of the biodegradable ACPS system. Using an animal model as a preclinical investigation, the prepared ACPS device was implanted into five mongrel dogs weighing over 30 kg to evaluate the detachment prevention effect of the ACPS system on polyether ether ketone (PEEK) cage after ACDF. By week 26, the molecular weight was decreased by 45.35% for the plate and 52.56% for the screw; the bending strength of the plate was decreased by approximately 26.2% when compared with the initial stage. The torsional yield strength and pullout strength of the screw was increased by 52.31% and 5.3%, respectively by week 2 and then subsequently decreased until week 26. No detachment or dislocation of the inserted PEEK cage was observed for 26 weeks in vivo study. These findings recommend that the ACPS system might be a promising biodegradable tool for the fixation of interbody implants and supporting the fusion in an ACDF model. Furthermore, additional clinical trials are planned for the future.