Growth and cloning of Tetrahymena pyriformis on solid meduium.
A method of obtaining clones of Tetrahymena pyriformis on solid medium has been developed. The medium consists of a basal layer of 1.5% agar topped with 2 ml of 0.3% agar in sterile, plastic petri plates (100 by 15 mm). Both agar layers contain either 2% proteose peptone and 0.1% liver extract (complex medium) or defined medium supplemented with proteose peptone. After drying, 0.5 ml of liquid culture is spread evenly over the top agar, and the plates are then sprinkled lightly and evenly with autoclaved dry Sephadex G-25 (fine). Cell colonies can be observed after 5 days of incubation either by viewing with a microscope or without the aid of a microscope after staining. Plating efficiency is high on either complex or defined medium with a number of strains of Tetrahymena, both micronucleate and amicronucleate. Colonies can be picked and transferred to liquid culture for further growth. The existence of clones was demonstrated by plating a mixture of two different drug-resistant mutants. The method should prove useful in selective procedures for the isolation of mutants and for determining survival after treatments such as ultraviolet irradiation.


Evaluation of 6 MALDI-Matrices for 10 μm Lipid Imaging and On-Tissue MSn with AP-MALDI-Orbitrap.
Mass spectrometry imaging is a technique uniquely suited to localize and identify lipids in a tissue sample. Using an atmospheric pressure (AP-) matrix-assisted laser desorption ionization (MALDI) source coupled to an Orbitrap Elite, numerous lipid locations and structures can be determined in high mass resolution spectra and at cellular spatial resolution, but careful sample preparation is necessary. We tested 11 protocols on serial brain sections for the commonly used MALDI matrices CHCA, norharmane, DHB, DHAP, THAP, and DAN in combination with tissue washing and matrix additives to determine the lipid coverage, signal intensity, and spatial resolution achievable with AP-MALDI. In positive-ion mode, the most lipids could be detected with CHCA and THAP, while THAP and DAN without additional treatment offered the best signal intensities. In negative-ion mode, DAN showed the best lipid coverage and DHAP performed superiorly for gangliosides. DHB produced intense cholesterol signals in the white matter. One hundred fifty-five lipids were assigned in positive-ion mode (THAP) and 137 in negative-ion mode (DAN), and 76 peaks were identified using on-tissue tandem-MS. The spatial resolution achievable with DAN was 10 μm, confirmed with on tissue line-scans. This enabled the association of lipid species to single neurons in AP-MALDI images. The results show that the performance of AP-MALDI is comparable to vacuum MALDI techniques for lipid imaging.


Patient-specific targeted bronchial thermoplasty: predictions of improved outcomes with structure-guided treatment.
Bronchial thermoplasty is a recent treatment for asthma in which ablative thermal energy is delivered to specific large airways according to clinical guidelines. Therefore, current practice is effectively "blind," as it is not informed by patient-specific data. The present study seeks to establish whether a patient-specific approach based on structural or functional patient data can improve outcomes and/or reduce the number of procedures required for clinical efficacy. We employed a combination of extensive human lung specimens and novel computational methods to predict bronchial thermoplasty outcomes guided by structural or functional data compared with current clinical practice. Response to bronchial thermoplasty was determined from changes in airway responses to strong bronchoconstrictor simulations and flow heterogeneity after one or three simulated thermoplasty procedures. Structure-guided treatment showed significant improvement over current unguided clinical practice, with a single session of structure-guided treatment producing improvements comparable with three sessions of unguided treatment. In comparison, function-guided treatment did not produce a significant improvement over current practice. Structure-guided targeting of bronchial thermoplasty is a promising avenue for improving therapy and reinforces the need for advanced imaging technologies. The functional imaging-guided approach is predicted to be less effective presently, and we make recommendations on how this approach could be improved. NEW & NOTEWORTHY Bronchial thermoplasty is a recent treatment for asthma in which thermal energy is delivered via bronchoscope to specific airways in an effort to directly target airway smooth muscle. Current practice involves the treatment of a standard set of airways, unguided by patient-specific data. We consider the potential for guided treatments, either by functional or structural data from the lung, and show that treatment guided by structural data has the potential to improve clinical practice.


The atomistic modeling of light-harvesting complexes from the physical models to the computational protocol.
The function of light-harvesting complexes is determined by a complex network of dynamic interactions among all the different components: the aggregate of pigments, the protein, and the surrounding environment. Complete and reliable predictions on these types of composite systems can be only achieved with an atomistic description. In the last few decades, there have been important advances in the atomistic modeling of light-harvesting complexes. These advances have involved both the completeness of the physical models and the accuracy and effectiveness of the computational protocols. In this Perspective, we present an overview of the main theoretical and computational breakthroughs attained so far in the field, with particular focus on the important role played by the protein and its dynamics. We then discuss the open problems in their accurate modeling that still need to be addressed. To illustrate an effective computational workflow for the modeling of light harvesting complexes, we take as an example the plant antenna complex CP29 and its H111N mutant.


Monitoring of Solar Irradiance in the High Andes.
Solar radiation has been measured in the high Andes near Laguna Lejia (latitude 23° 26' 23.30" S, longitude 67° 38' 14.29" W) at an elevation of 4715 m between December 2016 and December 2017. Irradiances were monitored in four wavelength channels: PAR (400-700 nm), UV-A (315-400 nm), UV-B (295-315 nm) and short-wavelength UV-B (295-310 nm) with a new radiometer. In addition, ambient temperatures were recorded. Record values have been found for PAR (exceeding 600 W m-2 ), UV-A (close to 95 W m-2 ), UV-B (3.13 W m-2 ) and short-wavelength UV-B (0.144 W m-2 ) during Austral spring. The winter irradiance values slightly exceeded 50% of these values. Maximal cloud effects due to multiple reflections were 45, 38, 32 and 35% higher than values under cloudless skies for PAR, UV-A, UV-B and short-wavelength UV-B, respectively. Record irradiance for this site shows a UV index reaching and exceeding 20, which is due to low solar zenith angles, the altitude, low water vapor and aerosol concentrations in the atmosphere as well as low total column ozone concentrations.


Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins.
The enormous bacterial load and mechanical forces in colon create a special requirement for protection of the epithelium. In the distal colon, this problem is largely solved by separation of the bacteria from the epithelium by a firmly attached inner mucus layer. In addition, an outer mucus layer entraps bacteria to be cleared by distal transport. The mucus layers contain a network of Muc2 mucins as the main structural component. Here, the renewal rate of the inner protective mucus layer was studied as well as the production and secretion of Muc2 mucin in the distal colon. This was performed by intraperitoneal injection of N-azidoacetyl-galactosamine (GalNAz) that was in vivo incorporated during biosynthesis of O-glycosylated glycoproteins. The only gel-forming mucin produced in the colon is the Muc2 mucin and as it carries numerous O-glycans, the granulae of the goblet cells producing Muc2 mucin were intensely stained. The GalNAz-labeled glycoproteins were first observed in the Golgi apparatus of most cells. Goblet cells in the luminal surface epithelium had the fastest biosynthesis of Muc2 and secreted material already three hours after labeling. This secreted GalNAz-labeled Muc2 mucin formed the inner mucus layer. The goblet cells along the crypt epithelium accumulated labeled mucin vesicles for a longer period and secretion of labeled Muc2 mucin was first observed after 6 to 8 h. This study reveals a fast turnover (1 h) of the inner mucus layer in the distal colon mediated by goblet cells of the luminal surface epithelium.


3D Assembly of MXene Networks using a Ceramic Backbone with Controlled Porosity.
Transition metal carbides (MXenes) are novel 2D nanomaterials with exceptional properties, promising significant impact in applications such as energy storage, catalysis, and energy conversion. A major barrier preventing the widespread use of MXenes is the lack of methods for assembling MXene in 3D space without significant restacking, which degrades their performance. Here, this challenge is successfully overcome by introducing a novel material system: a 3D network of MXene formed on a porous ceramic backbone. The backbone dictates the network's 3D architecture while providing mechanical strength, gas/liquid permeability, and other beneficial properties. Freeze casting is used to fabricate a silica backbone with open pores and controlled porosity. Next, capilary flow is used to infiltrate MXene into the backbone from a dispersion. The system is then dried to conformally coat the pore walls with MXene, creating an interconnected 3D-MXene network. The fabrication approach is reproducible, and the MXene-infiltrated porous silica (MX-PS) system is highly conductive (e.g., 340 S m-1 ). The electrical conductivity of MX-PS is controlled by the porosity distribution, MXene concentration, and the number of infiltration cycles. Sandwich-type supercapacitors with MX-PS electrodes are shown to produce excellent areal capacitance (7.24 F cm-2 ) and energy density (0.32 mWh cm-2 ) with only 6% added MXene mass. This approach of creating 3D architectures of 2D nanomaterials will significantly impact many engineering applications.


Efficacy and stability of AT TORBI 709 M toric IOL.
To describe the intraocular rotational stability and refractive results of the toric AT TORBI 709 M (former AT.Comfort 464 TLC) intraocular lens (IOL) (Carl Zeiss Meditec AG, Jena, Germany). Forty-eight eyes of 32 consecutive patients with cataract and greater than 1 diopter of corneal astigmatism were included. Implantation of the toric IOL was performed after phacoemulsification. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual refractive sphere, residual keratometric and refractive cylinders, and toric IOL axis were measured before and 1, 3, and 6 months after surgery. Mean logMAR UDVA and CDVA improved significantly after surgery (P < .05). UDVA was 20/40 or better in 88.1% of eyes and 20/25 or better in 61.9%. CDVA was 20/40 or better in 100% of eyes and 20/25 or better in 90.2%. Mean refractive cylinder decreased significantly from -2.23 ± 1.72 before to -0.43 ± 0.53 after surgery (P < .05). Vector analysis of attempted versus achieved correction showed 100% of eyes within ± 1.00 D and 95.2% within ± 0.50 D for J and 100% of eyes were within ± 1.00 D and 95.2% within ± 0.50 D for J. Mean toric IOL axis rotation was 4.42 ± 4.31 degrees (range: 0 to 16 degrees) and 86% of the lenses rotated less than 10 degrees. The AT TORBI 709 M IOL has proved to be a predictable and effective device with good rotational stability for the correction of preexisting astigmatism during cataract surgery.


Activity of cefazolin and two beta-lactamase inhibitors, clavulanic acid and sulbactam, against Bacteroides fragilis.
One hundred clinical isolates of the Bacteroides fragilis group of bacteria were tested by agar dilution for susceptibility to cefazolin alone or in combination with clavulanic acid or sulbactam. For cefazolin, the MIC for 50% of the isolates (MIC50) was 32 micrograms/ml, the breakpoint for susceptibility. With the addition of 0.5 micrograms of clavulanic acid per ml, the MIC for 90% of the isolates (MIC90) was 8 micrograms/ml, well within the achievable range of concentrations in serum or tissue. Similarly, with the addition of 0.5 micrograms of sulbactam per ml, the MIC90 was 16 micrograms/ml. The addition of a higher concentration (4.0 micrograms/ml) of clavulanic acid or sulbactam resulted in MIC90S which were fourfold lower than those with 0.5 micrograms/ml. A fixed ratio of cefazolin-beta-lactamase inhibitor of 4:1 resulted in an MIC50 and MIC90 which were intermediate between the 0.5- and 4.0-micrograms/ml fixed concentration of beta-lactamase inhibitor.


How to make an impact in surgical research: a consensus summary from the #SoMe4Surgery community.
Understanding and interpreting medical literature through critical thinking and applying this knowledge to evidence-based practice is an integral part of surgical training. Participating in research accelerates this process; however, young doctors' involvement in research may be suboptimal. Our aim was to provide young surgeons with recommendations on how to properly engage in surgical research. An online twitter conversation focused on recommendations about how a young physician can succeed in research was undertaken. Twitter activity for that conversation and hashtags was analyzed. A consensus based on the recommendations extracted from the discussion is summarized. Key opinion leaders were engaged to promote the conversation. Discussion was opened to all participants related to surgery or surgical research, including surgeons, medical students, nurses, patients, and healthcare workers. A total of 244 participants engaged in the Twitter conversation. The highest tweeted hashtags were #SoMe4Surgery and #SurgicalResearch with 855 and 847 tweets, respectively. Themes that came out of the conversation included 'Mentorship', which was the most essential recommendation. 'International collaboratives' and 'foreign research fellowship' were also deemed important factors for a successful path in research. Additionally, routine read of online journals, use of social media for scientific purposes, often engagement in manuscript drafting and proper time management were also recommended. Research is demanding and time consuming but an essential part of surgical education. We believe that any young surgeon can have greater chances to succeed in surgical research by following our recommendations and by academically using social media platforms.


Dynamic covalent polymers enabled by reversible isocyanate chemistry.
The design of responsive materials by introducing dynamic covalent bonds (DCBs), which can undergo reversible association and dissociation under certain conditions, is an appealing research field in recent years. Reversible isocyanate chemistry representatively consists of urethane, thiourethane, and urea bonds, all of which can reverse into their own starting chemicals (isocyanates and active hydrogen compounds) upon heating. In this article, we overview the mechanisms and experimental elements affecting the dynamic features of isocyanate-based bonds (IBs). With the knowledge of reversible isocyanate chemistry, the construction strategies of different dynamic covalent polymers including polyurethanes, polyureas, and polythiourethanes are discussed, in particular for dynamic polymer networks. The major applications of dynamic isocyanate-based polymers in recycling and self-healing materials, shape morphing polymers, 3D printing, and composites are outlined. The emergence of reversible isocyanate chemistry offers a highly effective platform to engineer thermally adaptable materials.


CT and MRI Findings of Inflammatory Myofibroblastic Tumor in the Bladder.
Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is a rare soft tissue tumor characterized by spindle cell proliferation with inflammatory cell infiltration. We present a case of bladder IMT occurring in a 6-year-old boy. Pretreatment CT images depicted a polypoid and broad-based mass measuring 18 mm in the superior to the front wall of the bladder, and the mass showed isodensity on precontrast image and ring enhancement of the mass after the intravenous administration of contrast material. Pelvic MRI demonstrated the 18 × 17 × 16 mm broad-based mass, suggesting submucosal tumor in the dome of the bladder. The mass showed low-to-moderate signal intensity on T1-weighted images and slight high signal intensity on T2-weighted images and restricted diffusion with low signal intensity on ADC map and abnormal high signal intensity on DWI. Transurethral resection of the bladder tumor and partial cystectomy were undertaken, and the pathology revealed IMT of the bladder. We suggest its inclusion in the differential diagnosis of cases of a polypoid and broad-based mass on the superior wall or the front wall of the bladder with ring enhancement on contrast-enhanced CT and MRI.


IL12B and IL23R polymorphisms are associated with alopecia areata.
Alopecia areata is an autoimmune disease in which activation of autoreactive T cells and inflammatory immune signals target the hair follicles autoantigens. Although cytokines are involved in regulating autoimmune inflammation, the specific involvement of these molecules in the pathogenesis of alopecia areata has been remained unsettled. Here, a possible influence of IL12B, IL17A, and IL23R variations on susceptibility to alopecia areata in Iranian patients was investigated. Genotyping of IL12B (rs3212227), IL17A (rs2275913), and IL23R (rs10889677) variants were performed by extracting genomic DNA from patients and controls. Gene expression was analyzed by real-time RT-PCR. The frequency of IL12B and IL23R gene polymorphisms is significantly higher in the patients than controls, while no significant difference was found for IL17A. Stratification of the patients with respect to age at disease onset indicated that CC genotype of IL12B (rs3212227) and AA genotype of IL23R (rs10889677) gene polymorphisms are significantly associated with late-onset alopecia areata disease. In contrast to IL17A and IL23R, IL12B gene expression levels elevated in patients to that of controls, but genotypes had no effect on levels of gene expression. Overall, our data confirmed that the IL12B and IL23R polymorphisms are associated with the risk to develop alopecia areata in our population.


Body image in obese women before, during, and after weight loss treatment.
Body image, as measured by the Appearance Evaluation and Body Areas Satisfaction scales of the Multidimensional Body-Self Relations Questionnaire (T.F. Cash, 1994b), was assessed in 59 obese women before, during, and after 48 weeks of weight loss treatment. Before treatment, positive ratings of body image were associated with higher levels of self-esteem, lower levels of dysphoria, and fewer previous diets. After 24 weeks and a mean weight loss of 19.4 kg (SD = 6.5), participants showed significant (p < .0001) improvements in body image. A small weight gain from Week 24 to Week 48 was associated with a slight but significant worsening in both measures of body image. Nevertheless, after 48 weeks and a mean weight loss of 16.3 kg (SD = 7.1), body image was significantly improved from baseline (p < .0001). Changes in body image were not related to changes in weight. Future studies are needed to separate the effects of treatment and weight loss on body image in obese persons.


Hypoxia after transarterial chemoembolization may trigger a progenitor cell phenotype in hepatocellular carcinoma.
To test the hypothesis that the hypoxia marker carbonic anhydrase IX (CAIX), and the cholangiocytic/progenitor markers cytokeratin (CK) 19 and epithelial cell adhesion molecule (EpCAM), may be expressed in areas of hypoxia in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Immunohistochemistry for CAIX, CK19 and EpCAM (BerEP4) was performed in 57 HCCs, including 40 residual/recurrent tumours adjacent to the TACE treatment site and 17 untreated tumours from the same 40 patients. CAIX was exxpressed in 19 of 40 residual/recurrent HCCs and in two of 17 untreated HCCs. The rate of CAIX immunoreactivity in the treated tumours was significantly higher than that in the non-treated tumours (47.5% versus 11.8%, P = 0.015). CK19 and EpCAM were expressed in six of 19 and in seven of 19 CAIX-positive TACE-treated HCCs, respectively, but were not expressed in CAIX-negative tumours or untreated tumours. There were significant associations between CK19 and CAIX immunoreactivity, and between EpCAM and CAIX immunoreactivity (P = 0.007 and P = 0.003, respectively). Double staining of CAIX and CK19 showed co-localization of both proteins in five of six cases. Three of seven EpCAM-positive tumours were also positive for CK19. Hypoxia may trigger the expression of proteins that are normally associated with cholangiocytic/progenitor cell differentiation, suggesting that TACE paradoxically causes an aggressive tumour phenotype.


[Detection of HBV specific cytotoxic lymphocytes responses in severe hepatitis B patients using MHC-peptide tetramer flow cytometry].
To explore the role played by HBV antigen specific cytotoxic lymphocytes (CTLs) in severe hepatitis B patients. Three kinds of HBV specific CD8+ T cells responding to HBV core 18-27, polymerase 575-583 and envelope 335-343 specific CD8+ T cells were searched with major histocompatibility complex (MHC)-peptide tetramer flow cytometry in the patients we studied. The cytokines produced by these specific CTLs such as IFNgamma, TNFalpha, IL-4, IL-10 were detected using ELISPOT assays. Their ability to lyse target cells was analyzed using a CytoTox96 Non-Radioactive Cytotoxicity Assay kit (Promega). The number of HBV core 18-27 specific CD8+ T cells was significantly higher in the peripheral blood of acute severe hepatitis B group patients than that in chronic severe hepatitis group (P less than 0.05), but lower than that in the acute hepatitis B patients. The IFNgamma and TNFalpha levels of acute severe hepatitis B patients were both significantly higher than those in the chronic severe hepatitis group (P less than 0.05). The ability to lyse target cells of HBV core 18-27 CTLs was also significantly higher in the acute severe hepatitis B group than that in the chronic severe hepatitis B group (P less than 0.05). The response to antigen stimulation was much higher in acute severe hepatitis B than in chronic severe hepatitis B patients. The specific CTLs persisted among the peripheral blood mononuclear cells in acute severe hepatitis B, which may be related to the viral clearance.


Selective degradation of mRNA: the role of short-lived proteins in differential destabilization of insulin-induced creatine phosphokinase and myosin heavy chain mRNAs during rat skeletal muscle L6 cell differentiation.
This investigation concerns the combined effects of removal and readdition of insulin and inhibition of protein and RNA synthesis on the stability of insulin-induced mRNAs during and after differentiation of rat L6A1 myoblast cells in culture. Addition of insulin accompanying the withdrawal of the mitogenic stimulus of serum to myoblasts caused an 80-fold increase in creatine phosphokinase (CK) activity which was largely accounted for by a similar increase in the amount of CK mRNA. The latter was co-ordinately induced with myosin heavy chain (MHC) mRNA but not malic enzyme (ME) mRNA. Measurements of steady-state levels of mRNA showed that removal of insulin caused CK mRNA, but not MHC mRNA, to be rapidly degraded, the effect being reversed upon readdition of the hormone. Direct measurement of 3H-labeled CK, MHC and beta-actin mRNAs confirmed the selective stabilization and destabilization of CK mRNA by the hormone. Conditions were established for a time-window during which cycloheximide (Cx) produced a virtually total arrest of protein synthesis in myotubes that was reversible upon removal of the inhibitor. Under these conditions, Cx selectively prevented the degradation of CK mRNA in a reversible manner. Actinomycin D (Act D) also arrested the loss of this mRNA. Under the same conditions of mRNA stabilization during de-induction, a superinduction of CK mRNA, but not MHC mRNA, was observed if the two inhibitors were added during induction in the continuous presence of insulin. We conclude that a short-lived protein(s), encoded by a short-lived mRNA(s), selectively regulates the stability of reversibly inducible mRNA.


Enteropathogenic Escherichia coli type III effectors alter cytoskeletal function and signalling in Saccharomyces cerevisiae.
Enteropathogenic Escherichia coli (EPEC) strains cause attaching/effacing lesions in enterocytes through the development of actin-supported pedestals at the site of bacterial adhesion. Pathogenesis requires a type III secretion system (TTSS), which injects into the host cell the intimin receptor, Tir, as well as other effectors called Esps (Escherichia secreted proteins). The genes encoding TTSS structural components and Esps are found within a pathogenicity island called the locus of enterocyte effacement (LEE). This paper describes the application of Saccharomyces cerevisiae as a model to probe the functions of LEE-encoded genes. In a systematic approach, the LEE-encoded translocator and effector proteins were endogenously expressed in yeast and their effects on cell growth, cytoskeletal function and signalling pathways were studied. EspD, EspG and Map inhibited growth by depolarizing the actin cortical cytoskeleton, whereas EspF expression altered the septin cytoskeleton. Specific yeast MAP kinase pathways were activated by EspF, EspG, EspH and Map. The yeast system was used to define functional domains in Map by expressing truncated versions; it was concluded that the C-terminal region of the protein is necessary for actin disruption and toxicity, but not for mitochondrial localization. The utility of the yeast model for functional analyses of EPEC pathogenesis is discussed.


A comparison of hospice vs conventional care of the terminally ill cancer patient.
Hospice is an alternative system of end-stage oncological care emphasizing palliative care, the patient and family as the unit of care, and the administration of care by an interdisciplinary team. Since its inception in the US in the early 1970s, hospice has evolved from a grass-roots social movement to a legitimate component of the health-care system, primarily serving a white, "young-old" cancer patient population under a variety of organizational arrangements. Data from the National Hospice Study compares medical and social service receipt by patients served in hospice and non-hospice settings during their last two weeks of life. Results indicate that patients served by conventional oncological care were more likely to receive diagnostic tests, chemotherapy, radiation therapy (for non-palliative purposes), surgery, and respiratory therapy than hospice patients. Social service interventions were more likely to be reported by hospice than non-hospice patients.


Potentiation of nitroglycerin-induced coronary dilatation by N-acetylcysteine.
Previous studies have suggested that (1) nitroglycerin causes vasodilatation by interacting with sulfhydryl groups in vascular smooth muscle, thereby activating guanylate cyclase and increasing the intracellular concentration of cyclic GMP, and (2) N-acetylcysteine, a source of sulfhydryl groups, potentiates the peripheral vasodilatory effect of nitroglycerin. This study was performed to explore the influence of N-acetylcysteine on nitroglycerin-induced coronary dilatation. In 18 patients (13 men and five women, 30 to 76 years old), coronary sinus blood flow (by thermodilution) was measured before and during intracoronary administration of nitroglycerin, 25 micrograms, both before and 5 min after a 15 min intravenous infusion of (1) 5% dextrose in water (n = 8, control) or (2) 100 mg/kg N-acetylcysteine (n = 10). Nitroglycerin caused no change in heart rate or systemic arterial pressure. In the control patients, coronary sinus blood flow behaved similarly during the two injections: it was 134 +/- 36 ml/min (mean +/- SD) before and 183 +/- 50 ml/min during injection No. 1 (average increase, 49 +/- 25 ml/min; average percent increase, 38 +/- 21%); and it was 131 +/- 34 ml/min before and 178 +/- 45 ml/min during injection No. 2 (average increase, 47 +/- 23 ml/min; average percent increase, 37 +/- 20%) (NS compared with injection 1). In the patients who received N-acetylcysteine, coronary sinus blood flow was 149 +/- 48 ml/min before and 191 +/- 54 ml/min during injection 1 (average increase, 42 +/- 15 ml/min; average percent increase, 30 +/- 12%) (NS compared with eight control values).(ABSTRACT TRUNCATED AT 250 WORDS)


Diagnosis of preclinical Alzheimer's disease in a clinical setting.
The aim of the study was to investigate whether the preclinical stage of Alzheimer's disease (AD) can be diagnosed in a clinical setting. To this end we investigated whether subjects with preclinical AD could be differentiated from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. Twenty-three subjects with preclinical AD, 44 subjects with nonprogressive mild cognitive impairment, and 25 subjects with very mild AD-type dementia were selected from a memory clinic population. Variables that were used to differentiate the groups were demographic variables, the Mini-Mental State Examination score, performance on cognitive tests, measures of functional impairment, and measures of noncognitive symptomatology. Age and the scores for the delayed recall task could best discriminate between subjects with preclinical AD and subjects with nonprogressive mild cognitive impairment. The overall accuracy was 87%. The score on the Global Deterioration Scale and a measure of intelligence could best discriminate between subjects with preclinical AD and subjects with very mild AD-type dementia. The overall accuracy was 85%. Subjects with preclinical AD can be distinguished from subjects with nonprogressive mild cognitive impairment and from subjects with very mild AD-type dementia. This means that preclinical AD is a diagnostic entity for which clinical criteria should be developed.


Pathogenesis of visna/maedi and caprine arthritis-encephalitis: new leads on the mechanism of restricted virus replication and persistent inflammation.
Lentiviruses are unique retroviruses which cause diseases with long incubation periods and prolonged clinical courses. The prototype lentiviruses, visna/maedi of sheep and arthritis-encephalitis virus of goats (CAEV), infect cells of the monocyte-macrophage system and replicate at a restricted level in these cells. The virus life cycle is closely associated with maturational factors in the cells; monocytes support the early stages of the replication cycle which goes to completion only when the cells mature to macrophages. Virus replication in the monocyte-macrophage results in lesions characterized by mononuclear cell infiltration of the central nervous system (CNS), lungs, synovium and mammary gland and their draining lymph nodes. Co-cultivation of sheep or goat lymphocytes with macrophages infected with visna or CAE viruses results in production of a unique interferon (LV-IFN). LV-IFN is a non-glycosylated protein of 54,000 to 64,000 daltons and has biological properties which have several implications for pathogenesis. Firstly, it retards the rate of maturation of monocytes and thus indirectly slows the rate of virus replication. Second, it restricts the rate of virus replication in mature macrophages by preventing virus maturation. Third, it induces expression of class II (Ia) antigens of the major histocompatibility complex on cells of macrophage lineage. Thus, by curtailing virus replication and enhancing expression of MHC class II antigens, LV-IFN may contribute to the induction and augmentation of the host's lymphoproliferative response to the virus.


Oral pulsatile delivery systems based on swellable hydrophilic polymers.
Upon contact with aqueous fluids, swellable hydrophilic polymers undergo typical chain relaxation phenomena that coincide with a glassy-rubbery transition. In the rubbery phase, these polymers may be subject to swelling, dissolution and erosion processes or, alternatively, form an enduring gel barrier when cross-linked networks (hydrogels) are dealt with. Because of the peculiar hydration and biocompatibility properties, such materials are widely exploited in the pharmaceutical field, particularly as far as hydrophilic cellulose derivatives are concerned. In oral delivery, they have for long been employed in the manufacturing of prolonged release matrices and, more recently, for pulsatile (delayed) release devices as well. Pulsatile delivery, which is meant as the liberation of drugs following programmed lag phases, has drawn increasing interest especially in view of emerging chronotherapeutic approaches. In pursuit of pulsatile release, various design strategies have been proposed, chiefly including reservoir, capsular and osmotic formulations. In most cases, water-swellable polymers play a key role in the overall delivery mechanism after being activated by physiological media. Based on these premises, the aim of the present review is to survey the main oral pulsatile delivery systems, for which swelling, dissolution and/or erosion of hydrophilic polymers are primarily involved in the control of release.


GBS-Based Genomic Selection for Pea Grain Yield under Severe Terminal Drought.
Terminal drought is the main stress that limits pea ( L.) grain yield in Mediterranean-climate regions. This study provides an unprecedented assessment of the predictive ability of genomic selection (GS) for grain yield under severe terminal drought using genotyping-by-sequencing (GBS) data. Additional aims were to assess the GS predictive ability for different GBS data quality filters and GS models, comparing intrapopulation with interpopulation GS predictive ability and to perform genome-wide association (GWAS) studies. The yield and onset of flowering of 315 lines from three recombinant inbred line (RIL) populations issued by connected crosses between three elite cultivars were assessed under a field rainout shelter. We defined an adjusted yield, which is associated with intrinsic drought tolerance, as the yield deviation from the value expected as a function of onset of flowering (which correlated negatively with grain yield). Total polymorphic markers ranged from approximately 100 (minimum of eight reads per locus, maximum 10% genotype missing data) to over 7500 markers (minimum of four reads, maximum 50% missing rate). Best predictions were provided by Bayesian Lasso (BL) or ridge regression best linear unbiased prediction (rrBLUP), rather than support vector regression (SVR) models, with at least 400-500 markers. Intrapopulation GS predictive ability exceeded 0.5 for yield and onset of flowering in all populations and approached 0.4 for the adjusted yield of a population with high trait variation. Genomic selection was preferable to phenotypic selection in terms of predicted yield gains. Interpopulation GS predictive ability varied largely depending on the pair of populations. GWAS revealed extensive colocalization of markers associated with high yield and early flowering and suggested that they are concentrated in a few genomic regions.


From macroscopic yield criteria to atomic stresses in polymer glasses.
The relationship between macroscopic shear yield criteria and local stress distributions in deformed polymer glasses is investigated via molecular dynamics simulations on different scales of coarse-graining. Macroscopic shear stresses at the yield point obey a pressure-modified von Mises (pmvM) criterion for many different loading conditions and strain rates. Average local stresses in small volume elements obey the same yield criterion for volumes containing approx. 100 atoms or more. Qualitatively different behavior is observed on smaller scales: the average octahedral atomic shear stress has a simple linear relationship to hydrostatic pressure regardless of macroscopic stress state and failure mode. Local plastic events are identified through a threshold in the mean-squared nonaffine displacement and compared to the local stress state. We find that the pmvM criterion only predicts local yield events when stress and displacements are averaged over at least 100 atoms. By contrast, macroscopic shear yield criteria appear to lose their ability to predict plastic activity on the atomic scale.


Ecosystem-based management of coastal zones in face of climate change impacts: Challenges and inequalities.
Climate change effects have the potential of affecting both ocean and atmospheric processes. These changes pose serious threats to the millions of people that live by the coast. Thus, the objective of the present review is to discuss how climate change is altering (and will continue to alter) atmospheric and oceanic processes, what are the main implications of these alterations along the coastline, and which are the ecosystem-based management (EBM) strategies that have been proposed and applied to address these issues. While ocean warming, ocean acidification and increasing sea level have been more extensively studied, investigations on the effects of climate change to wind and wave climates are less frequent. Coastal ecosystems and their respective natural resources will respond differently according to location, environmental drivers and coastal processes. EBM strategies have mostly concentrated on improving ecosystem services, which can be used to assist in mitigating climate change effects. The main challenge for developing nations regards gaps in information and scarcity of resources. Thus, for effective management and adaptive EBM strategies to be developed worldwide, information at a local level is greatly needed.


Healthcare leaders' views on successful quality improvement initiatives and context.
Purpose The purpose of this paper is to investigate the contextual factors contributing to the sustainability of healthcare quality improvement (QI) initiatives. Design/methodology/approach Themes from semi-structured interviews with international healthcare leaders are compared with Kaplan and Provost et al.'s (2012) model for understanding success in quality (MUSIQ). Critical success factors within these themes are shown in detail. Findings The interviews provide a rich source of information on critical success factors. The themes largely correspond with MUSIQ, reinforcing its robustness. An important factor emerging from the interviews was the importance of engagement with patients and families in QI, and this needs consideration in seeking to understand context in QI. Research limitations/implications Interview participants represent a limited set of western countries and health systems. Their experiences may not hold true in other settings. Practical implications The detail on critical success factors provides QI practitioners with guidance on designing and implementing sustainable initiatives. Originality/value Including consideration of contextual factors for engagement with patients and families in frameworks for context in QI appears to be an original idea that will add value to such frameworks. Researchers in patient engagement are starting to address contextual factors and connections should be made with this work.


Value of ctDNA methylation biomarkers in diagnosis of colorectal tumors.
Tweetable abstract DNA methylation alterations have been identified as promising biological markers for early-stage colorectal cancer detection. Here, the authors highlight some recent advances in DNA methylation and its role in the early diagnosis and overall disease course management of colorectal tumors. New insights into DNA methylation biomarkers for colorectal cancer early diagnosis and management are discussed.


[Early surgical treatment of cutaneous hemangiomas].
Infantile hemangioma appears after the birth as a vascular tumor, which is known for its characteristic evolution in 3 phases: rapid augmentation then stabilization and involution on several years with in the best cases, classical "restitutio ad integrum". Usual surgical attitude is abstention and surgery is proposed only in order to treat sequel. But some particular situations require early surgery for life-threatening lesions or in case of functional impairment. Surgery consists in these cases in a simple volumetric diminution of the tumor with no aim for esthetic improvement. Other kinds of hemangiomas require an early surgical treatment before their complete involution. In some particular locations, deformation or growth delay can occur due to the lesion's development. In some cases, hemangiomas present a delayed involution with minor regression capacity; these are mainly located on the median part of the face and have principally a subcutaneous development. Early surgery can be proposed in order to avoid definitive deformation or growth impairment of adjacent structures. It should be performed before school age and before occurrence of psychological difficulties. Surgery is indicated in a perspective of esthetic improvement. Surgical procedure consists first in modeling excision followed by simple repair technique as linear suture or purse string closure; complex surgical procedures inducing their own sequels are usually inappropriate.


Skin Cooling on Breath-Hold Duration and Predicted Emergency Air Supply Duration During Immersion.
PURPOSE: This study was intended to determine the effect of skin cooling on breath-hold duration and predicted emergency air supply duration during immersion.METHODS: While wearing a helicopter transport suit with a dive mask, 12 subjects (29 ± 10 yr, 78 ± 14 kg, 177 ± 7 cm, 2 women) were studied in 8 and 20°C water. Subjects performed a maximum breath-hold, then breathed for 90 s (through a mouthpiece connected to room air) in five skin-exposure conditions. The first trial was out of water for Control (suit zipped, hood on, mask off). Four submersion conditions included exposure of the: Partial Face (hood and mask on); Face (hood on, mask off); Head (hood and mask off); and Whole Body (suit unzipped, hood and mask off).RESULTS: Decreasing temperature and increasing skin exposure reduced breath-hold time (to as low as 10 ± 4 s), generally increased minute ventilation (up to 40 ± 15 L · min-1), and decreased predicted endurance time (PET) of a 55-L helicopter underwater emergency breathing apparatus. In 8°C water, PET decreased from 2 min 39 s (Partial Face) to 1 min 11 s (Whole Body).CONCLUSION: The most significant factor increasing breath-hold and predicted survival time was zipping up the suit. Face masks and suit hoods increased thermal comfort. Therefore, wearing the suits zipped with hoods on and, if possible, donning the dive mask prior to crashing, may increase survivability. The results have important applications for the education and preparation of helicopter occupants. Thermal protective suits and dive masks should be provided.Madu VC, Carnahan H, Brown R, Ennis K-A, Tymko KS, Hurrie DMG, McDonald GK, Cornish SM, Giesbrecht GG. Skin cooling on breath-hold duration and predicted emergency air supply duration during immersion. Aerosp Med Hum Perform. 2020; 91(7):578-585.


Subunit interface dynamics in hexadecameric rubisco.
Ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) plays an important role in the global carbon cycle as a hub for biomass. Rubisco catalyzes not only the carboxylation of RuBP with carbon dioxide but also a competing oxygenation reaction of RuBP with a negative impact on photosynthetic yield. The functional active site is built from two large (L) subunits that form a dimer. The octameric core of four L(2) dimers is held at each end by a cluster of four small (S) subunits, forming a hexadecamer. Each large subunit contacts more than one S subunit. These interactions exploit the dynamic flexibility of Rubisco, which we address in this study. Here, we describe seven different types of interfaces of hexadecameric Rubisco. We have analyzed these interfaces with respect to the size of the interface area and the number of polar interactions, including salt bridges and hydrogen bonds in a variety of Rubisco enzymes from different organisms and different kingdoms of life, including the Rubisco-like proteins. We have also performed molecular dynamics simulations of Rubisco from Chlamydomonas reinhardtii and mutants thereof. From our computational analyses, we propose structural checkpoints of the S subunit to ensure the functionality and/or assembly of the Rubisco holoenzyme. These checkpoints appear to fine-tune the dynamics of the enzyme in a way that could influence enzyme performance.


Cutaneous adenodermatofibroma: report of 2 cases.
Dermatofibromas (DFs) are common benign fibrohistiocytic lesions, mostly affecting young adults. Many types of DF have been described, depending on architectural, cellular, and stromal peculiarities. Recently, a peculiar type of benign cutaneous tumor showing hemosiderotic DF-like stroma and apocrine glands has been described. We report 2 additional cases of DF without hemosiderotic changes showing entrapped apocrine glandular structures. We speculate about the origin of the glandular component and propose the term adenodermatofibroma for this type of lesions.


Neuromuscular activation of triceps surae using muscle functional MRI and EMG.
The aim of the present study was to clarify the neuromuscular activation patterns among individual triceps surae (TS) muscles during a repetitive plantarflexion using muscle functional magnetic resonance imaging (MRI) (mfMRI) and electromyography (EMG). Six healthy men participated in this study, performing 5 sets of 10 repetitions of a calf-raise exercise bilaterally, unilaterally, and unilaterally with an additional 15% of body-weight load. The transverse relaxation times (T2) in the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) muscles were measured from mfMR images obtained with the subject at rest and immediately after exercise; integrated EMG (iEMG) activity was recorded from the same muscles during exercise using surface electrodes. There was remarkable correspondence between the changes in T2 values and iEMG activity under the three different workloads for individual TS muscles. In addition, changes in T2 value that occurred as a function of increasing exercise loads were linearly correlated with iEMG activity in the MG (r=0.58, P<0.05) and SOL (r=0.63, P<0.01), but not in the LG. These results suggest that 1) mfMRI signals and iEMG activity correlate with workload in individual TS muscles, 2) mfMRI signals are associated with neuromuscular activity reflected in iEMG in the MG and SOL but not in the LG, and 3) these relationships are associated with neuromuscular and metabolic factors during exercise.


Investigation of the Photocatalytic Activity of Electrospun and Surface-Modified PAN/α-FeOOH Nanofibers for the Degradation of Hazardous Azo Dyes.
Decoration of α-FeOOH nanorods over PAN nanofibers was performed using the electrospinning technique. The as-designed decorated nanofibers were characterized using various techniques such as wide-angle powder X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), Fourier transform infrared (FTIR) spectroscopy, UV-vis spectrophotometry (UV-vis), thermogravimetry analysis (TGA), N2 adsorption-desorption isotherm (BET), and X-ray photoelectron spectrometry (XPS). α-FeOOH NRs were decorated uniformly over PAN fibers, as observed from its morphological investigation, which shows novelty. 1D α-FeOOH nanorods with PAN nanofibers have not been studied for photocatalytic characteristics. No literature mentions that α-FeOOH nanorods coated in PAN NFs act as photocatalysts to degrade hazardous azo dyes. α-FeOOH nanorods on PAN NFs inhibit aggregation and increase dye binding, boosting photocatalytic performance. PAN/α-FeOOH NFs have a maximal specific surface area with a reduced bandgap than α-FeOOH NRs. PAN/α-FeOOH nanofibers showed excellent photocatalytic activity for the degradation of Trypan blue (TB) (120 min, 99.7%) and Eriochrome black T (EBT) dyes (160 min, 97.6%), respectively, under solar light irradiation. PAN/α-FeOOH NFs have the potential to be used in the degradation of azo dyes and the treatment of wastewater due to their low energy requirements and versatility.


Safety of ungated shockwave lithotripsy in pediatric patients.
Ungated extracorporeal shockwave lithotripsy (ESWL) in adults is associated with cardiac arrhythmias. We report on the safety and efficacy of this method for treatment of renal calculi in children. Children under 14 years with radio-opaque renal stones were treated by ungated ESWL. Pre-treatment plain radiographs and intravenous urography and post-treatment ultrasonography and plain films were used to follow up clearance of fragments. All children were monitored for arrhythmias. Thirty-seven children (28 males, nine females) with a median age of 5 years (range 2-14 years) underwent 69 ungated ESWL sessions for renal calculi. Nineteen children had stones located in the left kidney, 17 had stones located in the right kidney and one child had bilateral renal stones. The stone size ranged from 6 to 25 mm (mean 9.9 mm). Shockwave number ranged from 800 to 3650 (mean of 2500 shockwaves per session). All children underwent lithotripsy with a gradual incremental energy increase from 14 to 20 kV. No patient had cardiac arrhythmias or other intra-procedural complications. No patient required conversion to gated ESWL. The overall stone-free rate was 86%. The results suggest that ungated ESWL is safe in children under 14 years. The efficacy was comparable to that of gated ESWL from previously published series.


Kickboxing review: anthropometric, psychophysiological and activity profiles and injury epidemiology.
Kickboxing is one of the modern combat sports. The psychophysiological demands of a kickboxing competition require athletes to achieve high thresholds of several aspects of physical fitness. The aim of the current review is to critically analyse and appraise the kickboxer's anthropometric, physiological, physical and psychological attributes with the activity profile and injury epidemiology in order to provide practical recommendations for training as well as new areas of scientific research. The available information shows that both amateur and elite-level male kickboxers are characterized by a higher proportion of mesomorphy with a well-developed muscle mass and low body fat percentage. While there is some variation in the maximum oxygen uptake of kickboxers, moderate to high cardio-respiratory levels are reported for these athletes. Regardless of kickboxers' level, a high peak and mean anaerobic power output were reported. High-level kickboxing performance also requires well-developed muscle power in both the upper and lower limbs. Psychological factors contribute to success that requires high levels of self-confidence, motivation, dispositional hope and optimism, mental toughness/resiliency, and adaptive perfectionism. Psychological attributes also distinguished successful from less successful kickboxers. The activity-to-rest ratio was higher in elite (1:1) than both amateur and national-level (from 1:2 to 1:5) kickboxers, with no significant differences between rounds (round 1=1:4, and rounds 2 and 3=1:5) as well as between winners and losers in amateur and national-level simulated combats. These particular psychophysiological characteristics and performance aspects of kickboxers influence performance and could serve as guidance for training. Finally, kickboxing is characterized by chronic repetitive head trauma, which causes hypopituitarism due to traumatic brain injury (TBI). Future investigations into the physical, physiological and psychological characteristics related to age, gender and competitive levels of kickboxers are required to enrich the current knowledge and to help create the most suitable training programme.


A solitary fibrous tumor with concurrent meningioma at the same site: A case report and review of the literature.
The present study describes a case of a solitary fibrous tumor (SFT) concurrent with meningioma in the same anatomical region. The patient was admitted to Tianjin Huanhu Hospital (Tianjin, China) presenting with progressive eyesight impairment, dizziness and right hemiparesis. Cranial magnetic resonance imaging revealed two primary tumors co-occurring at the same site. One lesion was a solid lesion located in the left frontal convex with homogeneous enhancement, and was closely associated with the dura mater; thus, it was suspected that the lesion was a meningioma. The second lesion was cystic and solid with an irregular shape, and was located next to the first tumor; this lesion was believed to be a hemangiopericytoma or astrocytoma. The patient underwent a left temporoparietal craniectomy and a complete excision of the two tumors was achieved. Subsequent pathological examination of the resected tissues confirmed that the two tumors were a secretory meningioma and a SFT, respectively. Immunohistochemistry is important in differentiating SFTs from other tumors. Currently, a total tumor resection is the optimal treatment strategy when managing these rare lesions, often with no requirement for adjuvant post-operative therapy; however, long-term follow-up is essential to detect any signs of recurrence. The possibility of multiple tumors should be taken into consideration when performing clinical examination. To further understand the mechanisms underlying the occurrence of multiple intracranial tumors, further research is required, alongside an increased number of case reports.


A New Paradigm for Achieving a Rapid Antidepressant Response.
The substantive delay (often 4-6 weeks) between the commencement of an antidepressant and any discernible improvement in depressive symptoms is an ongoing concern in the management of depressive disorders. This delay incurs the risk of cessation of medication, self-harm/suicide and ongoing 'damage' to the brain caused by the illness. Both historically and now, off-label polypharmacy has been used in clinical practice in an attempt to facilitate both immediate- and long-term relief from symptoms. While somewhat effective, this strategy was unregulated and associated with severe adverse side effects for patients. In this article we proffer an alternative paradigm to achieve a more rapid antidepressant response by conceptualising the gap in terms of windows of response. The Windows of Antidepressant Response Paradigm (WARP) frames treatment response as windows of time in which a clinical response can be expected following initiation of an antidepressant. The paradigm defines three distinct windows-the immediate-response window (1-2 days), fast-response window (up to 1 week) and slow-response window (from 1 week onwards). Newer agents such as rapid-acting antidepressants are considered to act within the immediate-response window, whereas atypical antipsychotic augmentation strategies are captured within the fast-response window. The slow-response window represents the delay experienced with conventional antidepressant monotherapy. Novel agents such as esketamine and brexpiprazole are discussed as examples to better understand the clinical utility of WARP. This framework can be used to guide research in this field and aide the development of newer, more effective antidepressant agents as well as providing a strategy to guide the prescription of multiple agents in clinical practice.


[Neuropsychology of Tourette's disorder: cognition, neuroimaging and creativity].
Tourette's disorder is the result of fronto-striatal brain dysfunction affecting people of all ages, with a debut in early childhood and continuing into adolescence and adulthood. This article reviews the main cognitive, functional neuroimaging and creativity-related studies in a disorder characterized by an excess of dopamine in the brain. Given the special cerebral configuration of these patients, neuropsychological alterations, especially in executive functions, should be expected. However, the findings are inconclusive and are conditioned by factors such as comorbidity with attention deficit hyperactivity disorder and obsessive-compulsive disorder, age or methodological variables. On the other hand, the neuroimaging studies carried out over the last decade have been able to explain the clinical symptoms of Tourette's disorder patients, with special relevance for the supplementary motor area and the anterior cingulate gyrus. Finally, although there is no linear relationship between excess of dopamine and creativity, the scientific literature emphasizes an association between Tourette's disorder and musical creativity, which could be translated into intervention programs based on music.


A simplified method for studying fibrous proteins in psoriatic scales obtained by tape stripping.
Polyacrylamide gel electrophoretic investigations were carried out on solubilized proteins from psoriatic and normal stratum corneum obtained by adhesive tape stripping. The proteins in the scales adhering to the tape were solubilized by incubating the tape in 1% sodium dodecyl sulphate (SDS) solution. The electrophoretic behaviour of these solubilized proteins on SDS-polyacrylamide gel was compared with the alpha-fibrous proteins (keratin) of callus. The proteins isolated from callus of normal human heel showed six main bands which were similar to those of the keratin isolated by the 8 M urea-mercaptoethanol method. The lesional skin of forty-five psoriatic patients consistently showed nine main bands on polyacrylamide gels, but only two main bands were observed in the non-lesional, non-heel skin. Six of these nine bands had mobilities and relative intensities almost identical with those of alpha-keratin extracted by the mercaptoethanol method, but the other three bands had greater mobilities on the gels. These results suggest that this technique may have considerable potential for studying changes in alpha-keratin in patients with psoriasis and other disorders of keratinization.


Speciation of lead in environmental waters by preconcentration on a new fullerene derivative.
A novel fullerene derivative including a chelating group attached to the fullerene core has been prepared by photoreaction of C60 and sodium diethyldithiocarbamate (NaDDC) in toluene-methanol medium. The optimization of the synthesis procedure was monitored by UV-visible spectroscopy using the spectrum of C60 fullerene as reference; the new material, a C60-NaDDC monoadduct, showed a shoulder at 430 nm and an increase in the absorption band comprised between 425 and 500 nm. The solid was obtained by photolysis reaction in approximately 24 h, requiring further purification by preparative chromatography. Characterization of the brown product was accomplished by XRD and solid-state 13C MAS NMR; chemical modification was confirmed through the appearance of peaks close to the fullerene core peak located at 146.9 ppm, which can be assigned to carbon atoms of C60 that are covalently bonded to the diethyldithiocarbamate group to form a pyrrolidine ring-fused fullerene monoadduct. Using lead species as a model assessed the ability of the new material for the preconcentration of metallic and organometallic compounds, providing detection limits of 4-15 ng/L. The most interesting conclusions of the results were high adsorption efficiency, selectivity, and stability of the C60-NaDDC derivative (the packed material can be used for at least six months).


[Effect of cordycepin on CX43 expression in the corpus cavernosum of type II diabetes induced erectile dysfunction in rats].
To study the effect of cordycepin on the expression of connexin 43 (CX43) in the corpus cavernosum tissue of the ED rats with type II diabetic mellitus (DM). Forty male SD rats were fed with high-fat diet and injected intraperitoneally with STZ solution to induce type II DM, and then divided into 4 groups of an equal number: DM model control, low-dose cordycepin (10.0 mg/kg/d), high-dose cordycepin (30.0 mg/kg/d) and sildenafil positive control (5.0 mg/kg/d). Another 10 male SD rats were taken as blank controls and fed with normal diet. After 6 weeks of intervention, the sexual behavior of the rats was observed, the ratio of intra-cavernous pressure to mean arterial pressure (ICP/MAP) measured, and the corpus cavernosal tissue harvested for observation of the morphology and determination of the expression level of CX43 in the corpus cavernosum by immunohistochemistry. Compared with the DM model controls, the rats in the high-dose cordycepin group showed significantly improved latency and frequency of captures (P < 0.01), increased ICP/MAP ratio (P < 0.05), and improved morphology of the corpus cavernosal tissue. The expression of CX43 was found mainly in the smooth muscle cells of the penile corpus cavernosum, and dramatically higher in the high-dose cordycepin group than in the DM model controls (P < 0.01). Cordycepin can effectively improve the erectile function of type Ⅱ diabetic rats by up-regulating the expression of CX43 in the penile corpus cavernosum.


Effects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring.
The pharmacokinetic and pharmacodynamic effects of antiretroviral therapy may differ in older compared with younger subjects with HIV infection. We aimed to assess factors associated with plasma antiretroviral drug exposure, including age, within a large HIV-infected cohort undergoing therapeutic drug monitoring (TDM). Data from the Liverpool TDM Registry were linked with the UK Collaborative HIV Cohort (CHIC) Study. All TDM of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was included and in order to account for different antiretroviral drugs the plasma concentrations were standardized by group measurements according to drug, dosing and timing of TDM. Regression modelling was used to evaluate associations of drug exposure with age and clinical parameters, including hepatic transaminase results and time to antiretroviral treatment modification. Data from 3589 TDM samples were available from 2447 subjects. The greatest numbers of plasma concentrations were assessed for lopinavir (22.4%), efavirenz (18.5%), atazanavir (17.0%) and saquinavir (11.6%). As age increased, median standardized NNRTI concentrations remained constant, whereas PI concentrations increased (correlation coefficient 0.04, P = 0.033). In a regression analysis stratified by antiretroviral drug class, standardized plasma concentrations were significantly associated with age for PIs (0.05 increase in standard deviation of drug concentration with each 10 year increase in age, P = 0.044), but not for NNRTIs or other clinical parameters, including hepatic transaminase results or time to antiretroviral treatment modification. With increasing age, statistically significant rises in plasma PI exposure, but not NNRTI exposure, were observed. The clinical relevance of this observation merits further investigation.


An implanted electronic laryngeal prosthesis.
The authors present a preliminary progress report on their investigations dealing with the development of an implanted electronic laryngeal prosthesis system. Their initial observations indicate success in the design and fabrication of the implantable, retropharyngeal transducer and secondary induction coil elements. The surgical procedure for implantation is described, and the complications encountered during the first thirteen procedures are reported. These complications included five seromas, one postoperative abscess, one partial wound breakdown secondary to animal-inflicited traumn, and two anesthetic deaths at the time of follow-up radiographic procedures. Additional observations are presented regarding the acoustical output of the transducer in air and after implantation. Projections are made concerning the use of this laryngeal prosthesis system in human patients for vocal rehabilitation after total laryngectomy.


Digital vascular imaging and selective renin sampling in post-transplant hypertension. Which kidney is responsible?
Forty-four hypertensive transplant patients were investigated by digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity to attempt to identify those patients whose hypertension may be amenable to surgical treatment. Localization of renin hypersecretion was possible in 12 patients. In ten of these, hypersecretion originated from the native kidney and in two from the graft. Localization was possible in a significantly higher proportion of patients with severe hypertension (8 of 17), and all of these had native kidney hypersecretion. Bilateral nephrectomy may be indicated in these patients. No cases of functionally significant renal artery stenosis were identified. The other major types of abnormal vascular pattern found on digital vascular imaging, diffuse intra-renal arterial attenuation and lower pole hypoperfusion may be secondary to hypertension. This combined technique may be useful in the evaluation of post-transplant hypertension, especially when hypertension is severe.


Involvement of Two-Component Signaling on Bacterial Motility and Biofilm Development.
Two-component signaling is a specialized mechanism that bacteria use to respond to changes in their environment. Nonpathogenic strains of Escherichia coli K-12 harbor 30 histidine kinases and 32 response regulators, which form a network of regulation that integrates many other global regulators that do not follow the two-component signaling mechanism, as well as signals from central metabolism. The output of this network is a multitude of phenotypic changes in response to changes in the environment. Among these phenotypic changes, many two-component systems control motility and/or the formation of biofilm, sessile communities of bacteria that form on surfaces. Motility is the first reversible attachment phase of biofilm development, followed by a so-called swim or stick switch toward surface organelles that aid in the subsequent phases. In the mature biofilm, motility heterogeneity is generated by a combination of evolutionary and gene regulatory events.


Osteomyelitis of the hand.
Osteomyelitis of the hand is uncommon, but if not adequately and promptly treated the detrimental effects on hand function can be devastating. The majority of literature on osteomyelitis relates to the lower limb, but the principles of management are applicable to the hand, with good surgical debridement and culture-guided antimicrobial therapy. For osteomyelitis in general, antibiotic therapy of 4-6 weeks' duration (intravenous and/or oral) is typically recommended. In the hand, length and mode of antibiotic administration are still under study. V.


Dysprosody following acquired neurogenic impairment.
Dysprosody is typically associated with the dysarthrias following acquired neurogenic disturbance but it has also been associated with impairment to the cortex of the right cerebral hemisphere (Behrens, 1985). Currently there is little agreement in the clinical literature as to the locus or nature of processes involved in production and reception of prosody. This paper investigates the usefulness of two psycholinguistic models of prosody--involving "abstract" and "concrete" processes (Ladd & Cutler, 1983)--in accounting for dysprosody following motor pathway as well as cortical lesions. Four groups of 10 adult patients each participated in the study; the first group had sustained a right cerebral hemisphere cortical stroke, the second group had hypokinetic dysarthria, the third group had ataxic dysarthria, and the fourth group was normal controls. Acoustic analysis using the Kay VisiPitch/PC was conducted on pairs of matched noun phrase and noun compounds (e.g., greenhouse, green house), interrogative and declarative versions of sentences, and sentences spoken in each of four different emotional tones. Right cerebral hemisphere damaged subjects produced shorter durations than the other groups for each stimulus class. However, all of the subjects were able to use duration to signal temporal information for the lexical distinction between noun compounds and noun phrases. The results are consistent with a model of prosodic control which involves both cortical as well as physiological control processes. Current treatment for dysprosody is discussed in light of this new emphasis on cognitive control processes.


[Nuclear spin tomography and computerized tomography in malignant hypernephroma].
Forty patients with histologically confirmed hypernephromas were examined by MR and CT. As regards T-staging, MR had an accuracy of 97% and CT of 91%; for N-staging, MR had an accuracy of 85% and CT of 91% and, with regard to infiltration of the renal vein, MR was correct in 88% of cases and CT in 81%. MR was most accurate in the pre-operative assessment of tumour spread, demonstrating caval involvement in 100% and lymph node metastases in 97%. On the other hand, infiltration of the renal pelvis could be assessed in only 65% of cases; in 27% the assessment was not possible and in 8% one could not be certain. CT proved to be at its best for staging of lymph nodes, but in 15% it was not possible to identify infiltration of the renal vein. MR was not greatly superior to CT in the preoperative diagnosis and staging of hypernephromas.


Phosphatidylcholine and cholesteryl esters identify the infiltrating behaviour of a clear cell renal carcinoma: 1H, 13C and 31P MRS evidence.
This study presents a multinuclear (1H, 13C and 31P) magnetic resonance spectroscopy characterization of the total lipid fraction extracted from different regions of a human kidney affected by a clear cell renal carcinoma. It was thus possible to demonstrate that cholesteryl esters and phosphatidylcholine are markers of the tumor infiltration, histologically confirmed, in the kidney medulla. The tumor tissue contains twice the amount of phosphatidylcholine compared to normal cortex. The results appear relevant in light of new clinical applications based on the biochemical composition of human tissues.


[Correspondence between spectral power and synchronization of the brain rhythms in the norm and cognitive pathology].
The work is aimed at the study of correlations between the measures of spectral power and cortical interactions of EEG rhythms in healthy subjects and schizophrenic patients ("acute" and chronic cases). All brain rhythms in healthy subjects appeared to be symmetrical and synchronous both in phase and frequency. In "acute" schizophrenics, opposite to healthy subjects, the distribution of cortical activity is asymmetrical, and in the chronic cases, the spectral power of most cortical rhythms is decreased as compared to healthy subjects. In the "acute" patients, interhemispheric connections are absent in all rhythms but alpha. In the chronic patients, the number of cortical connections is slightly higher than in the acute patients; and they are located in the posterior areas in the gamma rhythm. These neurophysiological aberrations evidently underlie the multiple mental activity disorders in schizophrenic patients. Thus, the correspondence between the brain rhythms and their synchronization is a necessary condition for normal perception, emotions and cognition evidently influencing behavior and consciousness.


Influence of genetic polymorphisms on biomarkers of exposure and effects in children living in Upper Silesia.
This article is a follow-up to our previous molecular epidemiology studies on the DNA damage in children from the Upper Silesia region of Poland. It is expected that metabolic and DNA repair gene polymorphisms may modulate individual susceptibility to environmental exposure. In this study, we investigate the association between polymorphisms of metabolising (CYP2D, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) and DNA repair (XPD, XRCC1, XRCC3) genes and selected biomarkers of exposure and effect such as levels of 1-hydroxypyrene (1-OHP) and urinary mutagenicity, aromatic DNA adducts, sister chromatid exchange (SCE) and micronuclei (MN) in 74 children. Both 1-OHP concentration and urinary mutagenicity tested by TA98+S9 were significantly higher in individuals with EPHX1 (exon 4) Arg/Arg genotype than in individuals with other genotype. The EPHX1 (exon 3) significantly affected urinary mutagenicity tested with strain YG1024+S9. The urinary mutagenicity in individuals with Tyr/Tyr homozygotes was lower than in individuals with Tyr/His and His/His (1057±685 vs. 1432±1003 revertants/mol creatinine). XRCC3 Met/Met genotype was associated with significantly higher levels of 1-OHP in urine compared with only The/Met genotype. The PAH-DNA adduct levels in the subgroup with GSTM1 null genotype was 2-fold higher than in individuals with GSTM1 active (7.06±5.12 vs. 13.14±9.81 adduct/10(8) nucleotides). The mean level of aromatic DNA adducts in children with deletion of the GSTT1 gene was significantly higher compared with individuals with that gene present (8.03±6.23 vs. 14.66±10.70 adduct/10(8) nucleotides). Also the carriers of the XPD Lys/Lys genotype showed higher levels of DNA adducts than heterozygotes (13.16±9.70 vs. 6.81±5.86 adducts/10(8) nucleotides). Children carrying the XRCC3-241 Met/Met genotype exhibited a higher number of SCE in peripheral blood lymphocytes than carriers of Thr/Met allele (8.15±0.86 vs. 7.62±0.79 SCE/cell). It was also observed that children with the GSTP1 slow conjugator had significantly elevated MN in peripheral blood lymphocytes compared with fast conjugator (4.23±3.49 vs. 6.56±5.00 MN/1000 cells).


Breastfeeding: perceived barriers and benefits/enhancers in a rural and urban setting.
This study investigated differences in perceived benefits/enhancers and barriers between women who planned to breastfeed, those who were uncertain, and those who did not plan to breastfeed. The volunteers were obtained from rural (60) and urban (82) public health department prenatal clinics. Fifty-three percent of the women were married, the average age was 23 years, 25% had not graduated from high school, 38% were black, and 46% were planning to return to work. The breastfeeding inventory consisted of 13 items to measure benefits and enhancers, 15 to measure barriers, and an open-ended question. Cronbach's alphas for internal consistency for benefits and enhancers and barriers were 0.88 and 0.83 respectively. Analysis of variance found significant differences among the three groups on perceived benefits and barriers. Rural and urban differences existed in perceived benefits/enhancers, but not in perceived barriers. In a multiple discriminant function analysis that included demographic characteristics, the most important predictor of breastfeeding decision was perceived benefits.


Roles of endogenous leukotrienes in damage caused by ethanol in isolated rat gastric cells.
The activity of prostaglandin (PG) and leukotriene (LT) synthesis and the role of endogenous LT in cellular resistance were assessed in isolated parietal and nonparietal cells of rats. Rat gastric cells were isolated and the fractions rich (F1) and poor (F2) in parietal cells were obtained. In F1, more PGE2, PGI2 (measured as the stable metabolite 6-keto-PGF1 alpha), and sulfidopeptide (SP)-LTs and less thromboxane A2 (TXA2, measured as the stable metabolite TXB2) were synthesized than in F2. AA861, an inhibitor of 5-lipoxygenase, inhibited the synthesis of SP-LTs in both fractions in a dose-related way. AA861 alone at any concentrations used did not affect the viability of the cells, but prevented the cell damage caused by ethanol in both fractions, the effect of AA861 being inhibited by indomethacin. These results suggest that in rat stomach, PGs and LTs, except TX, are synthesized mainly in parietal cells rather than in nonparietal cells. Endogenous LT may play a crucial role in the development of cellular damage caused by ethanol independently of systemic and extracellular factors. The balance of PG and LT may be important for regulation of cellular resistance.


Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor.
Hibernating mammals use reduced metabolism, hypothermia, and stored fat to survive up to 5 or 6 mo without feeding. We found serum levels of the fat-derived ketone, D-beta-hydroxybutyrate (BHB), are highest during deep torpor and exist in a reciprocal relationship with glucose throughout the hibernation season in the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Ketone transporter monocarboxylic acid transporter 1 (MCT1) is upregulated at the blood-brain barrier, as animals enter hibernation. Uptake and metabolism of 13C-labeled BHB and glucose were measured by high-resolution NMR in both brain and heart at several different body temperatures ranging from 7 to 38 degrees C. We show that BHB and glucose enter the heart and brain under conditions of depressed body temperature and heart rate but that their utilization as a fuel is highly selective. During arousal from torpor, glucose enters the brain over a wide range of body temperatures, but metabolism is minimal, as only low levels of labeled metabolites are detected. This is in contrast to BHB, which not only enters the brain but is also metabolized via the tricarboxylic acid (TCA) cycle. A similar situation is seen in the heart as both glucose and BHB are transported into the organ, but only 13C from BHB enters the TCA cycle. This finding suggests that fuel selection is controlled at the level of individual metabolic pathways and that seasonally induced adaptive mechanisms give rise to the strategic utilization of BHB during hibernation.


Toward the elimination of lymphatic filariasis by 2020: treatment update and impact assessment for the endgame.
Lymphatic filariasis (LF) is an important public health problem endemic in 73 countries, where it is a major cause of acute and chronic morbidity and a significant impediment to socioeconomic development. It is targeted for elimination by 2020, through preventive chemotherapy using albendazole in combination with either ivermectin or diethylcarbamazine citrate. Preventive chemotherapy enables the regular and coordinated administration of safe, single-dose medications delivered through mass drug administration (MDA). Many countries are now scaling down MDA activities after achieving 100% geographic coverage and instituting monitoring and evaluation procedures to establish the impact of several consecutive rounds of MDA and determine if transmission has been interrupted. At the same time, countries yet to initiate MDA for elimination of LF will adopt improved mapping and coverage assessment protocols to accelerate the efforts for achieving global elimination by 2020. This review provides an update on treatment for LF and describes the current global status of the elimination efforts, transmission control processes and strategies for measuring impact and continuing surveillance after MDA has ceased.


Comparison of sonoelastography with sonourethrography and retrograde urethrography in the evaluation of male anterior urethral strictures.
Retrograde urethrography (RUG) is the most common and preferred imaging modality for imaging of the anterior urethral strictures despite its well-known limitations and disadvantages. Sonourethrography (SUG) was introduced in 1988 to overcome the limitations of RUG and to provide more accurate results. As proper selection of imaging modality is very important for planning the treatment, various advances in this area are required. One of the major factors for recurrence of stricture disease is spongiofibrosis. Sonoelastography (SE) is a newer technique, tried in various other pathologies. In this study, we have used this technique for the first time to assess its efficacy in the evaluation of anterior urethral stricture disease by comparison with RUG and SUG. Between August 2014 and May 2015, 77 patients with clinical features of anterior urethral stricture disease were included in the study and evaluated by RUG followed by SUG and SE for stricture location, length, depth of spongiofibrosis and periurethral pathologies. The results were then correlated with operative and histopathological findings. Overall diagnostic accuracy of SE, SUG, and RGU for the estimation of stricture location, and length were estimated 92.68% vs. 91.54%, 79% vs. 78.87% and 80.48% vs. 43.66%, respectively, while for depth of spongiofibrosis SE, and SUG had accuracy rates of 87.3%, 48%, respectively. The mean length measured on SE was nearest to the mean intra-operative stricture length (21.34+11.8 mm). SE findings significantly correlated with the colour of bladder mucosa on cystoscopic examination (p=0.003) whereas the association was non-significant (p=0.127) for difficulty in incision. While a nonsignificant correlation existed between SUG findings related both to the colour of the bladder mucosa and difficulty in incision on cystoscopy, SE findings had a significant association (p<0.001) with histopathology findings for severe degree of fibrosis. Sonoelastography estimates stricture site and length better in comparison with RUG and SUG. It estimates degree of spongiofibrosis which serves as an important prognostic factor for stricture recurrence more accurately than SUG.


Nippostrongylus brasiliensis in young rats. Lymphocytes expel larval infections but not adult worms.
Young rats were not able to expel adult N. brasiliensis infections even when the worms were damaged by antibodies and the young rats were given all the cellular components (sensitized lymphocytes and bone marrow cells) shown to be necessary for the expulsion of antibody-damaged worms from adult rats. In contrast, most of the worms were expelled from young rats given sensitized lymph node cells on the day of a larval infection. These results show that the reduced ability of young rats to respond to infection by producing sensitized lymphocytes only partly explains their inability to expel the worms. It was not possible to explain the failure of young rats to expel adult worms by hypothesizing that they develop an active factor which prevents the cells from acting on the worms. It is also unlikely that worms persist in young rats because they differ in their susceptibility to cells compared with antibody-damaged worms from mature rats. This work suggests that the immune mechanism which affects the immature stages of this nematode may differ from that which controls the adult stages.


Elucidation of toll-like receptor and adapter protein signaling in vascular dysfunction induced by gram-positive Staphylococcus aureus or gram-negative Escherichia coli.
Pathogens contain specific pathogen-associated molecular patterns, which activate pattern recognition receptors of the innate immune system such as Toll-like receptors (TLRs). Although there is a clear evidence of how macrophages sense pathogens, we know less about such processes in vessels. This is critical to understand because activation of vascular cells and the subsequent induction of inflammatory genes by bacteria are crucial events in the development of septic shock. In the current study we have used genetically modified mice to investigate the role of TLRs, adapter proteins, tumor necrosis factor alpha (TNFalpha), and nitric oxide synthase II (NOSII) in vascular dysfunction induced by Gram-positive (Staphylococcus aureus) or Gram-negative (Escherichia coli) bacteria. Our data show that Gram-positive S. aureus or Gram-negative E. coli causes vascular dysfunction via the induction of NOSII. For S. aureus, this process requires TLR2, TLR6, myeloid differentiation factor 88 (MyD88) adapter-like, MyD88, and TNF, but not TLR4 or TLR1. Vascular dysfunction induced by E. coli requires TLR4 but has no requirement for TLR2, TLR1, TLR6, or TNF, and a partial but incomplete requirement of MyD88 and TIR domain-containing adapter inducing interferon-beta. Staphylococcus aureus induced NOSII protein expression in vascular smooth muscle cells but not in macrophages, whereas E. coli induced NOSII in both cell types. Our data are the first to establish the definitive roles of specific TLRs in the sensing of Gram-positive and Gram-negative bacteria by vessels and demonstrate that macrophages and blood vessels may differ in their response to pathogens.


Synthesis of alkylcarbonate analogs of O-acetyl-ADP-ribose.
The non-hydrolyzable alkylcarbonate analogs of O-acetyl-ADP-ribose have been synthesized from the phosphorylated ribose derivatives after coupling with AMP morpholidate promoted by mechanical grinding. The analogs were assessed for their ability to inhibit the human sirtuin homolog SIRT1.


[The Importance of Vector Management for Prevention of Hospital Infections].
Many researches show that cockroaches, ants, some other arthropods and also rodents in hospitals, can act as potential vectors of medically important bacteria, fungi and parasites. The results of microbiological studies show that these animals play a significant role in the epidemiology of hospital infections. These vectors may be found inside of the kitchens, patient rooms, toilets, medicine stores, canteen and wards in health care environments. The importance of vector control in order to prevent the spread of nosocomial infections in healthcare facilities was discussed in this paper. This study also gives information on integrated control methods for vectors in hospitals.


Proton-minibeam radiation therapy: a proof of concept.
This Monte Carlo simulation work aims at studying a new radiotherapy approach called proton-minibeam radiation therapy (pMBRT). The main objective of this proof of concept was the evaluation of the possible gain in tissue sparing, thanks to the spatial fractionation of the dose, which could be used to deposit higher and potentially curative doses in clinical cases where tissue tolerances are a limit for conventional methods. Monte Carlo simulations (GATE v.6) have been used as a method to calculate the ratio of the peak-to-valley doses (PVDR) for arrays of proton minibeams of 0.7 mm width and several center-to-center distances, at different depths in a water phantom. The beam penumbras were also evaluated as an important parameter for tissue sparing, for example, in the treatment of non-cancer diseases like epilepsy. Two proton energies were considered in this study: a clinically relevant energy (105 MeV) and a very high energy (1 GeV), to benefit from a reduced lateral scattering. For the latter case, an interlaced geometry was also evaluated. Higher or similar PVDR than the ones obtained in x-rays minibeam radiation therapy were achieved in several pMBRT configurations. In addition, for the two energies studied, the beam penumbras are smaller than in the case of Gamma Knife radiosurgery. The high PVDR obtained for some configurations and the small penumbras in comparison with existing radiosurgery techniques, suggest a potential gain in healthy tissue sparing in this new technique. Biological studies are warranted to assess the effects of pMBRT on both normal and tumoral tissues.


Effect of lipid raft disruption on ethanol inhibition of l1 adhesion.
Alcohol causes fetal alcohol spectrum disorders in part by disrupting the function of the neural cell adhesion molecule L1. Alcohol inhibits L1-mediated cell-cell adhesion in diverse cell types and inhibits L1-mediated neurite outgrowth in cerebellar granule neurons (CGNs). A recent report indicates that ethanol (EtOH) induces the translocation of L1 into CGN lipid rafts and that disruption of lipid rafts prevents EtOH inhibition of L1-mediated neurite outgrowth. The same butanol-pentanol cutoff was noted for alcohol-induced translocation of L1 into lipid rafts that was reported previously for alcohol inhibition of L1 adhesion, suggesting that EtOH might inhibit L1 adhesion by shifting L1 into lipid rafts. The NIH/3T3 cell line, 2A2-L1s , is a well-characterized EtOH-sensitive clonal cell line that stably expresses human L1. Cells were treated with 25 mM EtOH, 5 μM filipin, or both. Lipid rafts were enriched in membrane fractions by preparation of detergent-resistant membrane (DRMs) fractions. Caveolin-1 was used as a marker of lipid rafts, and L1 and Src were quantified by Western blotting in lipid-raft-enriched membrane fractions and by immunohistochemistry. EtOH (25 mM) increased the percentage of L1, but not Src, in 2A2-L1s membrane fractions enriched in lipid rafts. Filipin, an agent known to disrupt lipid rafts, decreased the percentage of caveolin and L1 in DRMs from 2A2-L1s cells. Filipin also blocked EtOH-induced translocation of L1 into lipid rafts from 2A2-L1s cells but did not significantly affect L1 adhesion or EtOH inhibition of L1 adhesion. These findings indicate that EtOH does not inhibit L1 adhesion in NIH/3T3 cells by inducing the translocation of L1 into lipid rafts.


Oxidized Soybean Oil Evoked Hepatic Fatty Acid Metabolism Disturbance in Rats and their Offspring.
The oxidation of fats and oils is an undisputed subject of science, given the effect of oxidized fats and oils on food quality and safety. This study aimed to determine whether maternal exposure to oxidized soybean oil (OSO) causes lipid metabolism disorders in the liver and whether this lipid metabolism disorder can be transmitted to offspring or even worsened. A total of 60 female Sprague-Dawley (SD) rats were divided randomly into four groups in this study. Treatment groups received a pure diet of OSO with a peroxide value of 200, 400, or 800 mEqO2/kg, while the control group received fresh soybean oil (FSO). As for our results, OSO affected serum biochemical parameters in the maternal generation (F0) and induced liver histopathology changes, inflammation, and oxidative stress. Moreover, the expression of genes related to the liver X receptor α (LXRα)─sterol regulatory element binding protein-1c (SREBP-1c) signaling pathway was changed. Similar trends were found in the livers of offspring on postnatal days 21 and 56. In conclusion, exposure to OSO during gestation and lactation can affect liver lipid synthesis. Additionally, it is detrimental to the development of the offspring's liver, affecting fatty acid metabolism and causing liver damage.


DJ-1 protein protects dopaminergic neurons against 6-OHDA/MG-132-induced neurotoxicity in rats.
Parkinson disease (PD) is the second most common neurodegenerative disease, and it cannot be completely cured by current medications. In this study, DJ-1 protein was administrated into medial forebrain bundle of PD model rats those had been microinjected with 6-hydroxydopamine (6-OHDA) or MG-132. We found that DJ-1 protein could reduce apomorphine-induced rotations, inhibit reduction of dopamine contents and tyrosine hydroxylase levels in the striatum, and decrease dopaminergic neuron death in the substantia nigra. In 6-OHDA lesioned rats, uncoupling protein-4, uncoupling protein-5 and superoxide dismutase-2 (SOD2) mRNA and SOD2 protein were increased when DJ-1 protein was co-injected. Simultaneously, administration of DJ-1 protein reduced α-synuclein and hypoxia-inducible factor 1α mRNA and α-synuclein protein in MG-132 lesioned rats. Therefore, DJ-1 protein protected dopaminergic neurons in two PD model rats by increasing antioxidant capacity and inhibiting α-synuclein expression.


Dual-Mode Gas Sensor Composed of a Silicon Nanoribbon Field Effect Transistor and a Bulk Acoustic Wave Resonator: A Case Study in Freons.
In this paper, we develop a novel dual-mode gas sensor system which comprises a silicon nanoribbon field effect transistor (Si-NR FET) and a film bulk acoustic resonator (FBAR). We investigate their sensing characteristics using polar and nonpolar organic compounds, and demonstrate that polarity has a significant effect on the response of the Si-NR FET sensor, and only a minor effect on the FBAR sensor. In this dual-mode system, qualitative discrimination can be achieved by analyzing polarity with the Si-NR FET and quantitative concentration information can be obtained using a polymer-coated FBAR with a detection limit at the ppm level. The complementary performance of the sensing elements provides higher analytical efficiency. Additionally, a dual mixture of two types of freons (CFC-113 and HCFC-141b) is further analyzed with the dual-mode gas sensor. Owing to the small size and complementary metal-oxide semiconductor (CMOS)-compatibility of the system, the dual-mode gas sensor shows potential as a portable integrated sensing system for the analysis of gas mixtures in the future.


Changes in polyamine pattern are involved in floral initiation and development in Polianthes tuberosa.
In the day-neutral plant Polianthes tuberosa (cv. Double) putrescine and spermine in corms at the early floral initiation stage decreased by 26 and 36%, respectively, compared with that in the vegetative stage. In contrast, a sharp increase in spermidine and cadaverine titers in corms was recorded at the early floral initiation stage. However, cadaverine in corms disappeared at the flower development stage. Polyamines in the roots were generally lower than those in the leaves and corms. In no case was the change in endogenous polyamine titers in the roots and leaves associated with floral initiation and flower development in P. tuberosa. Exogenous application of spermidine at 5, 25 or 150 microg per plant at the vegetative stage did not affect flower primordium counts. However, addition of a spermidine synthase inhibitor, cyclohexylamine, at 150 or 250 microg per plant (each dose was applied two times in total at an interval of 4 days) significantly reduced flower primordium counts, indicating that spermidine is involved in floral initiation and floral development in P. tuberosa. In P. tuberosa corms at the vegetative stage arginine decarboxylase activity rises and decreases at the early floral initiation stage. In contrast, ornithine decarboxylase activity reaches the highest level at the early floral initiation stage and declines significantly at the vegetative stage. Results indicate that an increase in spermidine and a transient increase in cadaverine titers in the corms seem characteristic of early floral initiation in P. tuberosa. It is also suggested that a significant reduction in putrescine and spermine in the corms is involved in the early floral initiation in P. tuberosa.


Oxidative stress and sarcomeric proteins.
Oxidative stress accompanies a wide spectrum of clinically important cardiac disorders, including ischemia/reperfusion, diabetes mellitus, and hypertensive heart disease. Although reactive oxygen species (ROS) can activate signaling pathways that contribute to ischemic preconditioning and cardioprotection, high levels of ROS induce structural modifications of the sarcomere that impact on pump function and the pathogenesis of heart failure. However, the precise nature of the redox-dependent change in contractility is determined by the source/identity of the oxidant species, the level of oxidative stress, and the chemistry/position of oxidant-induced posttranslational modifications on individual proteins within the sarcomere. This review focuses on various ROS-induced posttranslational modifications of myofilament proteins (including direct oxidative modifications of myofilament proteins, myofilament protein phosphorylation by ROS-activated signaling enzymes, and myofilament protein cleavage by ROS-activated proteases) that have been implicated in the control of cardiac contractility.


[Implementing next-generation sequencing for precision hematology/oncology].
In January 2015, President Obama announced his plan to launch the Precision Medicine Initiative. While precision medicine originally refers to a medical model wherein treatments are tailored to individual patients based on their lifestyle, genetic background, and other molecular and physiological test results, genomics-based oncology is most advanced in terms of clinical implementation. Herein, I discuss the benefit of cancer genome sequencing in the field of hematology/oncology and the associated technical and sociomedical challenges.


[Meningioma in psychiatry. Clinico-pathologic contribution to differential cerebral organic psychosyndrome diagnosis in middle and advanced age].
A clinico-pathological follow-up of mentally ill patients of the Rheinische Landesklinik Düsseldorf between 1960 and 1984 revealed intracranial space-occupying processes in 47 of 1023 post mortem examinations (4.6%). 9 of the 47 cases (19%) were meningiomas. 5 patients of those clinically not diagnosed as having meningioma had signs of raised intracranial pressure at post mortem, in 4 others the meningioma was in incidental finding of presumably lacking clinical significance. 4 other meningioma patients were diagnosed while alive; 2 of them were operated on the tumor. Short- and longterm psychiatric features of meningioma patients bear many similarities with mental symptoms due to other causes in middle and old age with also similar problems in differential diagnosis. There is no raised incidence of meningioma among patients presenting psychiatrically. "Endoform" features in psychopathology are rarely encountered in meningioma patients. According to the pertinent literature an operation in due time ameliorates or abolishes predominantly psychiatric illness in about 80% of meningioma patients.