Long-term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood.
Atmospheric carbon dioxide (CO2 ) levels are currently at 418 parts per million (ppm), and by 2100 may exceed 900 ppm. The biological effects of lifetime exposure to CO2 at these levels is unknown. Previously we have shown that mouse lung function is altered by long-term exposure to 890 ppm CO2 . Here, we assess the broader systemic physiological responses to this exposure. Mice were exposed to either 460 or 890 ppm from preconception to 3 months of age, and assessed for effects on developmental, renal and osteological parameters. Locomotor, memory, learning and anxiety-like behaviours of the mice were also assessed. Exposure to 890 ppm CO2 increased birthweight, decreased female body weight after weaning, and, as young adults, resulted in reduced engagement in memory/learning tasks, and hyperactivity in both sexes in comparison to controls. There were no clear anxiety, learning or memory changes. Renal and osteological parameters were minimally affected. Overall, this study shows that exposure of mice to 890 ppm CO2 from preconception to young adulthood alters growth and some behaviours, with limited evidence of compensatory changes in acid-base balance. These findings highlight the potential for a direct effect of increased atmospheric CO2 on mammalian health outcomes. KEY POINTS: Long-term exposure to elevated levels of atmospheric CO2 is an uncontrolled experiment already underway. This is the first known study to assess non-respiratory physiological impacts of long-term (conception to young adulthood) exposure of mice to CO2 at levels that may arise in the atmosphere due to global emissions. Exposure to elevated CO2 , in comparison to control mice, altered growth patterns in early life and resulted in hyperactive behaviours in young adulthood. Renal and bone parameters, which are important to balance acid-base levels to compensate for increased CO2 exposure, remained relatively unaffected. This work adds to the body of evidence regarding the effects of carbon emissions on mammalian health and highlights a potential future burden of disease.


Isolation of Bovine Neutrophils by Fluorescence- and Magnetic-Activated Cell Sorting.
Flow cytometry and magnetic bead technology enable the separation of cell populations with the highest degree of purity. Here, we describe protocols to sort bovine neutrophils from blood, the labeling and sorting, including gating strategies. We also provide advice to preserve neutrophil viability and detail a protocol to measure phagocytosis and oxidative species production.


Longitudinal Reference Ranges for Tricuspid Annular Plane Systolic Excursion and Mitral Annular Plane Systolic Excursion in Normally Grown Fetuses.
The aim of this study was to construct reference ranges for fetal tricuspid annular plane systolic excursion (TAPSE) and mitral annular plane systolic excursion (MAPSE) using conventional M-mode ultrasound (US) in the second half of pregnancy. Participants underwent US scans every 4 weeks from 18 weeks' gestation until delivery. The TAPSE and MAPSE were measured by conventional M-mode US at each examination. The relationships between TAPSE and MAPSE and gestational age and estimated fetal weight were modeled by Bayesian mixed effects linear regression. Positive linear relationships were observed between both MAPSE and TAPSE and gestational age and estimated fetal weight. Reference centiles for TAPSE and MAPSE were developed. This simple technique is a useful tool for assessing cardiac function and could be used for quantitative assessments of fetal cardiac function, particularly in high-risk pregnancies such as those complicated by maternal diabetes.


Lung ultrasound-guided therapy reduces acute decompensation events in chronic heart failure.
Pulmonary congestion is the main cause of hospital admission in patients with heart failure (HF). Lung ultrasound (LUS) is a useful tool to identify subclinical pulmonary congestion. We evaluated the usefulness of LUS in addition to physical examination (PE) in the management of outpatients with HF. In this randomised multicentre unblinded study, patients with chronic HF and optimised medical therapy were randomised in two groups: 'PE+LUS' group undergoing PE and LUS and 'PE only' group. Diuretic therapy was modified according to LUS findings and PE, respectively. The primary endpoint was the reduction in hospitalisation rate for acute decompensated heart failure (ADHF) at 90-day follow-up. Secondary endpoints were reduction in NT-proBNP, quality-of-life test (QLT) and cardiac mortality at 90-day follow-up. A total of 244 patients with chronic HF and optimised medical therapy were enrolled and randomised in 'PE+LUS' group undergoing PE and LUS, and in 'PE only' group. Thirty-seven primary outcome events occurred. The hospitalisation for ADHF at 90 day was significantly reduced in 'PE+LUS' group (9.4% vs 21.4% in 'PE only' group; relative risk=0.44; 95% CI 0.23 to 0.84; p=0.01), with a reduction of risk for hospitalisation for ADHF by 56% (p=0.01) and a number needed to treat of 8.4 patients (95% CI 4.8 to 34.3). At day 90, NT-proBNP and QLT score were significantly reduced in 'PE+LUS' group, whereas in 'PE only' group both were increased. There were no differences in mortality between the two groups. LUS-guided management reduces hospitalisation for ADHF at mid-term follow-up in outpatients with chronic HF.


Is an ovulation-inducing factor (OIF) present in the seminal plasma of rabbits?
The objectives of this study were (1) to determine the effect of rabbit seminal plasma on LH secretion and ovulation using the llama animal model as an in vivo ovulation bioassay and (2) to determine the effect of llama or rabbit seminal plasma on ovulation induction in the rabbit model. In Experiment 1, llamas with a growing follicle ≥8mm in diameter were assigned randomly to one of three groups (n=5 per group) and given an intramuscular dose of 1mL of: (a) llama seminal plasma, (b) rabbit seminal plasma, or (c) phosphate buffered saline (PBS; negative control). Blood samples for LH measurement were taken every 15 min from 1.5 h before to 8 h after treatment (Day 0: starting of treatment). Llamas were examined by ultrasonography every 12h from treatment to ovulation, and then every other day until Day 16 after treatment to evaluate corpus luteum (CL) development. Blood samples for progesterone measurement were taken every other day from Day 0 to Day 16. Ovulation was detected in 4 of 5, 5 of 5, and 0 of 0 llamas treated with llama or rabbit seminal plasma and PBS, respectively (P<0.001). After treatment, plasma LH concentration increased and decreased (P<0.01) in the llama and rabbit seminal plasma group but not in the PBS-treated group. No differences were observed on CL development (P≥0.3) and progesterone secretion (P>0.05) between both seminal plasma treated groups. In Experiment 2, receptive female rabbits (n=5-7 per group) were given an intramuscular dose of: (a) 0.5, (b) 1.0 and (c) 2.0mL of either rabbit or llama seminal plasma, (d) 0.5mL PBS (negative control), or (e) 25μg of gonadoreline acetate (GnRH; positive control). Does were submitted to laparotomy 24-36 h after treatment to determine the ovulatory response and the presence of antral and hemorrhagic anovulatory follicles. Ovulation sites (7.0±0.6) were only detected in GnRH-treated does (P<0.01). There was an increase (P<0.01), in the total number of follicles (antral plus hemorraghic follicles) in those females treated with 1mL of rabbit seminal plasma and there was a tendency (P=0.08) for more hemorrhagic anovulatory follicles in does treated with 1.0 and 2.0mL of either rabbit or llama seminal plasma. Results document the presence of OIF in the seminal plasma of rabbits. The differential ovulatory response between species, however, requires further investigation.


Unexpected Tumor: Primary Asymptomatic Schwannoma in Thyroid Gland.
The discovery of a tumor as a primary schwannoma in the thyroid gland is rare (Andrion et al. in Virchows Arch 413:367-372, 1988). It represents less than 1 % of mesenchymal neoplasms of this gland. Therefore, few cases of this type are described in medical literature (Aron et al. in Cytopathology 16:206-209, 2005; Cashman et al. in Medscape J Med 10(8):201, 2008; Coleman et al. in AJR Am J Roentgenol 140:383-7, 1983). In this article, we introduce the clinical case of a 27-year-old female patient, who presented a nodular mass located in the neck region. This mass was not associated with other symptoms and during the imagistic investigation it appeared to be a thyroglossal duct cyst. A fine needle aspiration biopsy was performed which revealed benign mesenchymal cells. After a pathology study of the piece resected through a thyroidectomy, it was confirmed that the tumor had neural characteristics, the final diagnosis being a primary schwannoma. The importance of a cytology study is emphasized, since in this case, it made it possible to accurately diagnose a mesenchymal tumor, despite their low frequency. It constitutes a highly useful tool for diagnosing non-epithelial neoplasia of the thyroid gland.


Effect of anhydrosophoradiol-3-acetate of Calotropis gigantea (Linn.) flower as antitumoric agent against Ehrlich's ascites carcinoma in mice.
Over 60% of currently used anti-cancer agents are derived in one-way or another from natural sources, including plants, marine organisms and microorganisms. Calotropis gigantea (Linn.) (Family: Asclepiadaceae) is a perennial shrub and it is used as a traditional folk medicine for the treatment of various health complications. But there is no report on isolation of anticancerous chemicals from the flower of Calotropis gigantea. The objective of the present study is to explore the antitumor effect of anhydrosophoradiol-3-acetate (A3A), isolated from the flower of Calotropis gigantea (Linn.) against Ehrlich's ascites carcinoma (EAC) in Swiss albino mice. Antitumoric effect of A3A was assessed by evaluating viable tumor cell count, survival time, body weight gain due to tumor burden, hematological and biochemical (glucose, cholesterol, triglyceride, blood urea, SALP, SGPT and SGOT) parameters of EAC bearing host at doses of 10 and 20 mg/kg body weight. Treatment with A3A decreased the viable tumor cells and body weight gain thereby increasing the life span of EAC bearing mice. A3A also brought back the altered hematological (Hb, total RBC and total WBC) and biochemical parameters more or less to normal level. Results of this study conclude that in vivo the A3A was effective in inhibiting the growth of EAC with improving in cancer induced complications.


Novel triazoles of 3-acetylbetulin and betulone as anticancer agents.
The CuAAC reaction of azides and acetylenic triterpenes was used for synthesis of new triazoles of 3-acetylbetulin and betulone. The triazole derivatives were evaluated for their anticancer activity in vitro against amelanotic melanoma C-32, ductal carcinoma T47D and glioblastoma SNB-19 cell lines. 28-[1-(3'-Deoxythymidine-5'-yl)-1H-1,2,3-triazol-4-yl]carbonylbetulone 6e exhibited a significant IC50 value (0.17 µM) against the human glioblastoma SNB-19 cell line, an almost 5-fold higher potency while compared with reference cisplatin.


Editorial overview: Carbohydrate-protein interactions and glycosylation: Glycan synthesis and recognition: finding the perfect partner in a sugar-coated life.
Oligosaccharides expressed on the surface of cells and in biological fluids as glycoproteins, glycolipids, proteoglycans and polysaccharides can be recognized by partner proteins, and these interactions have been shown to mediate fundamental biological events such as occur in the immune system, signal transduction, development and cancer metastasis. The specificities of these partner proteins (lectins) for their glycan ligands are determined by factors such as glycan composition, shape and density of expression and the involvement of the aglycone moiety as part of the recognition motif. There is increasing knowledge on the mechanisms of these interactions as new secondary binding sites continue to be elucidated adding to the functional awareness of sugar-binding proteins. This issue focuses on recent advances in understanding how C-type lectins in the immune system work, how novel motifs involving asymmetric glycan branch recognition and protein-protein interactions influence critical biological functions including signal transduction and bactericidal pore formation, recent studies on novel glycan-binding proteins produced by bacteriophage, analysis of the interactions between heparin/heparan sulphate and their binding proteins, and recent findings on the molecular interactions between chondroitin-dermatan sulphate and various bioactive protein components. We conclude with a review on a recent fascinating class of processive enzymes responsible for synthesis of high-molecular weight extracellular polysaccharides such as hyaluronic acid, chitin and alginate.


Immediate GTP hydrolysis upon FtsZ polymerization.
To understand the polymerization dynamics of FtsZ, a bacterial cell division protein similar to tubulin, insight is required into the nature of the nucleotide bound to the polymerized protein. In a previous study, we showed that the FtsZ polymers contain mostly GDP. A recent study challenged this result, suggesting that the polymerized FtsZ is in a GTP-bound state. Here, we show that, when radiolabelled [gamma-32P]-GTP is used to polymerize FtsZ, GTP is hydrolysed instantaneously. The FtsZ polymer contains both GDP and the radiolabelled inorganic phosphate.


The effect of re-audit and education on antibiotic prescribing practice at Causeway Hospital, Northern Ireland.
Antimicrobial resistance is a growing global problem. There has been increasing emphasis on promoting antimicrobial stewardship. Accurate completion of antibiotic prescriptions, such as documentation of clinical indication and a stop/review date, helps promote antimicrobial stewardship. To investigate the impact of educational interventions on the completeness of antibiotic prescriptions at Causeway Hospital surgical unit. Inpatient drug prescription charts were audited to monitor the completeness of antibiotic prescriptions on the surgical unit. Two educational interventions were implemented, with a subsequent prospective re-audit carried out. The completion of (1) "Stop date/Review date", (2) "What infection are you treating?", (3) "Cultures sent?", (4) "Printed name", (5) "Professional number", and (6) "Bleep number" fields within the inpatient drug charts increased noticeably in the re-audit. A paired t test, comparing all of the initial audit completion proportions with the re-audit completion proportions, demonstrated a statistically significant improvement (p < 0.05). Educational interventions led to an improvement in the completeness of antibiotic prescriptions. This highlights the important role that continued audit and education play in the promotion of antimicrobial stewardship.


Hyaluronic acid delayed inflammatory reaction after third dose of SARS-CoV-2 vaccine.
Treatments based on hyaluronic acid represent one of the most largely used practice of esthetic medicine. In the literature, it has already been described delayed reaction after vaccine like flu vaccine mediated by T-lymphocytes. We report three cases of dermal filler reactions following mRNA vaccination against SARS-CoV-2; all the patients had received the filler months or even years before the vaccine. Patient one: A 60-year-old female patient that was treated one year ago in the lip developed swelling days after getting mRNA Pfizer Biotech vaccine. She received her booster of Pfizer vaccination one week before. Patient two: A 45-year-old female patient treated in the lip two years before developed angioedema days after getting her booster of Pfizer Biotech vaccine. In this case, it was necessary to prescribe cortisone per os. Patient three: A 40-year-old female patient treated for the nasolabial fold five months before developed erythema and edema after receiving the booster of Moderna Vaccine. As demonstrated in our three case reports, even the booster of vaccine can cause delayed inflammatory reactions in patients that have previously received fillers. Delayed inflammatory reactions in patients that have received filler in the past are uncommon and usually self-limited. Those are the first example reported in the literature of reaction after the booster dose without any previous symptoms.


Changes in diversity, abundance, and structure of soil bacterial communities in Brazilian Savanna under different land use systems.
The Brazilian Savanna, also known as "Cerrado", is the richest and most diverse savanna in the world and has been ranked as one of the main hotspots of biodiversity. The Cerrado is a representative biome in Central Brazil and the second largest biome in species diversity of South America. Nevertheless, large areas of native vegetation have been converted to agricultural land including grain production, livestock, and forestry. In this view, understanding how land use affects microbial communities is fundamental for the sustainable management of agricultural ecosystems. The aim of this work was to analyze and compare the soil bacterial communities from the Brazilian Cerrado associated with different land use systems using high throughput pyrosequencing of 16S rRNA genes. Relevant differences were observed in the abundance and structure of bacterial communities in soils under different land use systems. On the other hand, the diversity of bacterial communities was not relevantly changed among the sites studied. Land use systems had also an important impact on specific bacterial groups in soil, which might change the soil function and the ecological processes. Acidobacteria, Proteobacteria, and Actinobacteria were the most abundant groups in the Brazilian Cerrado. These findings suggest that more important than analyzing the general diversity is to analyze the composition of the communities. Since soil type was the same among the sites, we might assume that land use was the main factor defining the abundance and structure of bacterial communities.


Bridging the gap - biomimetic design of bioelectronic interfaces.
Applied bioelectronic interfaces have an enormous potential for their application in personalized medicine and brain-machine interfaces. While significant progress has been made in the translational applications, there are still concerns about the safety and compliance of artificial devices interacting with cells and tissues. Applying biomimetic design principles enables developing new devices with improved properties in terms of their signal transduction efficiency and biocompatibility. Learning from the paradigms of biological architecture, we can define four cornerstones of biomimetics, which can guide designing new bioelectronic devices or providing improved solutions to challenging biomedical problems. Recent progress shows how these paradigms were successfully employed, for example, to create neuron-like electronics and assemble electronic materials in situ onto the cell membranes using genetic targeting.


An improved method for the differential assay of 3-O-methylated catecholamines in human urine using ion-pair extraction and gas chromatography electron capture detection.
A gas chromatographic method is described for the quantitative determination of urinary normetadrenaline, metadrenaline and 3-methoxytyramine using electron capture detection. The N,O-dipentafluoropropionyl beta-O-ethyl derivatives of normetadrenaline and metadrenaline and the N,O-dipentafluoropropionyl derivative of 3-methoxytyramine were prepared. The amines were purified by ion exchange chromatography and ion pair extraction. Amine derivatives from urine extracts were identified definitively by mass fragmentography. The 24-h excretion value for normetadrenaline in human urine is 167 +/- 95 micrograms (mean +/- S.D.), for metadrenaline is 116 +/- 74 micrograms (mean +/- S.D.) and for 3-methoxytyramine is 82 +/- 68 micrograms (mean +/- S.D.).


Expression profile of immunoregulatory factors in canine tumors.
Cancers utilize a variety of molecules to escape host immune responses. Better understanding the immune environment surrounding cancer may facilitate application of innovative cancer immunotherapies, such as immune checkpoint inhibitors, to dogs as well as humans. In this study, we screened the expression of 20 immune regulatory molecules in diverse canine tumors (n = 59). Quantitative RT-PCR (qPCR) analysis revealed that some immune regulatory molecules, such as LGALS9 (coding Galectin-9) and CD48, were expressed in most canine tumors, but other molecules, such as CD274 (coding PD-L1), IL4I1, PVR, TNFSF18, ICOSLG, and TNFSF4, were rarely expressed. NECTIN2 was highly expressed in epithelial tumors but was low in non-epithelial tumors. In contrast, VSIR and CD200 expressions were low in epithelial tumors but high in non-epithelial tumors. Interestingly, several tumors expressed distinctive immunoregulatory factors. Hepatocellular carcinomas expressed FGL1, mast cell tumors expressed PDCD1LG2 (coding PD-L2), transitional cell carcinomas expressed VTCN1 (coding B7x), and lymphomas and squamous cell carcinomas expressed CD70. Consistent with qPCR results, immunofluorescence staining confirmed that hepatocellular carcinomas expressed FGL-1 protein. Thus, this study reveals the expression profile of immunoregulatory molecules in canine tumors and opens the door to better understanding the relationship between canine tumors and host immunity.


Childhood trauma, peer victimization, and non-suicidal self-injury among Chinese adolescents: a latent variable mediation analysis.
Childhood and peer experiences can influence adolescents' perceptions of interpersonal relationships, which can, in turn, influence their emotional states and behavior patterns. Non-suicidal self-injury (NSSI) is now a common problem behavior among adolescents. The present study examined the role of childhood trauma and peer victimization in adolescents' NSSI. A cross-sectional survey was conducted among 1783 adolescents (1464 girls and 318 boys) in the psychiatric outpatient clinics or wards of 14 psychiatric hospitals or general hospitals in nine provinces in China. Data were collected using the Multidimensional Peer Victimization Scale (MPVS), Short-form Childhood Trauma Questionnaire(CTQ-SF), and Functional Assessment of Self-Mutilation (FASM). Structural equation modeling (SEM) with latent variables was used to demonstrate the mediating role of peer victimization in the association between childhoodtrauma and NSSI. The SEM analysis demonstrated that peer victimization plays a partial mediating role in the relationship between childhood trauma and NSSI. In addition, several covariates (such as age, gender, education level, and place of residence) effectively regulated the relationship between peer victimization and NSSI. In future studies of NSSI among Chinese adolescents, attention should be paid to the roles of childhood trauma and peer bullying; there is a temporal sequence between these two variables and, to some extent, childhood trauma can have an impact on bullying during adolescence which, in turn, influences NSSI behavior.


Dissipation rates, residue distribution, degradation products, and degradation pathway of sulfoxaflor in broccoli.
Broccoli was selected as the research object in this paper to reveal the dissipation, distribution, and degradation pathway of sulfoxaflor under greenhouse and open-field cultivation conditions for the ecological risk assessment of sulfoxaflor. Results showed that the dissipation of sulfoxaflor in broccoli leaves, flowers, stems, roots, and the whole broccoli was in accordance with the first-order kinetic equation. The sulfoxaflor concentration in broccoli roots reached the maximum value after 1 day of application and then gradually decreased. The degradation half-lives of sulfoxaflor in the roots, leaves, flowers, stems, and whole broccoli were between 2.3 and 19.8 days. The longest degradation half-life of sulfoxaflor was in Heilongjiang under greenhouse cultivation. The terminal residue of sulfoxaflor in broccoli was in the range of 0.005-0.029 mg/kg, and the proportion of sulfoxaflor residue in broccoli leaves was the largest. Thirteen transformation products were separated and identified by ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and their kinetic evolution was studied. The cleavage of the N = S bond, C-S bond, C-O bond, and cyanide, as well as glucosylation, hydroxylation, SO extrusion, elimination, sulfhydrylation, ketonization, defluorination, and rearrangement, was inferred as the mechanism. Overall, these results can provide guidance for the supervision of the safe application of sulfoxaflor.


Integrating in-bed gas looping and CO2 capture in the FeD-Latrine.
Sanitation equity and climate actions are world concerns stated by the United Nations in the Sustainable Development Goals. A significant source of greenhouse gas emissions is inputted by human wastes, either in developing countries through wastewater treatment plants, or in the underdeveloped world, through anaerobic digestion of fecal sludge in pit latrines. For the first time, an integrated process for CO2 reduction and capture is implemented in a thermally sustainable, latrine-like device that destroys fresh human feces using smoldering combustion, the FeD-Latrine. A gas looping oxidizes combustible gases and creates favorable conditions to capture CO2 in bed. CH4 and H2 molar fractions are decreased around 90 % and 30 %, respectively. CaO used as a sorbent captures up to 8 mmol of CO2 per gram, forming a stable CaCO3. Compared to kinetic-dominant processes for CO2 capture, we obtain an efficiency of around 52 %. Our findings show that using the FeD-Latrine to replace typical pit latrines reduces 60 % of the CO2-eq emissions.


Molecular weight and structural studies on cephalopod rhodopsin.
The protein moiety of squid (Watasenia scintillans) rhodopsin has been shown to have a molecular weight of 46 800 by means of amino acid analysis. This value was comparable to the value (51 000) obtained from SDS-polyacrylamide gel electrophoresis. After the squid eyes were incubated at 10 degrees C for 8 days, the rhodopsin showed a molecular weight of 39 000 on electrophoresis. The smaller molecular weight was ascertained by amino acid analysis of the rhodopsin; and may result from autolysis by the lysosomal enzyme. The rhodopsin in rhabdomeric membranes and in detergent solution was treated with chymotrypsin, papain or subtilisin. These enzymes first produced the 39 000 dalton rhodopsin and then cleaved this into the 25 000 and 14 000 dalton peptides without bleaching. The rhodopsin was attacked by proteases and readily lost an approx. 12 000 dalton peptide portion. This portion included the COOH-terminal and was rich in glutamic acid, proline, glycine, alanine and tyrosine residues.


Autoradiographic determination of regional brain glucose content.
Brain glucose content is an important experimental variable that affects the value of the "lumped constant" of the 2-deoxyglucose method. The apparent volume of distribution in brain of the nonmetabolizable glucose analog, 3-O-methylglucose, depends only on the glucose content. From the kinetic constants of glucose transport and the apparent volume of distribution, we used autoradiography to calculate the regional glucose content of the normal rat brain. The regional glucose content varied only insignificantly in gray matter regions; the average glucose content of all rat brain slices examined was 4 mumol g-1, with an average plasma glucose concentration of 8.6 mM. Regional values varied between 3.4 and 4.6 mumol g-1. Thus, there is no reason to believe that the regional values of the lumped constant vary significantly in normal rat brains.


Cutaneoarticular mucormycosis due to Cunninghamella bertholletiae in a patient with AIDS.
A case of mucormycosis in an AIDS patient is reported. The infection was located in the skin and knee joint after open trauma of the left thigh. Cunninghamella bertholletiae was isolated. The prognosis of this infection is ominous in patients with AIDS because of their precarious immunologic status.


High seroprevalence of human herpesvirus 8 (HHV-8) in HIV-1-infected pregnant women of Southeastern Italy: association with injection drug use and hepatitis C virus infection.
The seroprevalence of human herpesvirus 8 (HHV-8) in a group of HIV-1-infected pregnant women and in mother-child pairs from Southeastern Italy (Apulia) was determined. Blood was collected from 49 HIV-1-infected women during pregnancy or at delivery as well as from their children. Samples were analysed for the presence of antibodies to the latency-associated nuclear antigen and a structural antigen encoded by open reading frame 65. The presence of antibodies to hepatitis C virus (HCV) was also determined. Nineteen women (38.7%) were found to be positive for HHV-8 antibodies to at least one of the two antigens, and 21 (42.9%) for HCV antibodies. HHV-8 antibodies were more common in injecting drug users (56.3%) than in women infected through heterosexual intercourse (30.3%). HCV antibodies were significantly more prevalent in HHV-8-seropositive (66.7%) than HHV- 8-seronegative (29%) women. Thirteen children born to HIV-1/HHV-8 co-infected women were HHV-8-seroreactive, with a variable pattern of reactivity to the analysed antigens. Follow-up of children showed a prolonged persistence of antibodies, in two cases for more than 12 months. This study has provided serological evidence for a high rate of HHV-8 infection in HIV-1-infected women in the Apulia region, and has identified a possible association between HHV-8 infection, past use of injection drugs and HCV infection. Parenteral transmission may, therefore, be a mode of virus spread.


Targeted Mass Spectrometry Analysis of Protein Phosphorylation by Selected Ion Monitoring Coupled to Parallel Reaction Monitoring (tSIM/PRM).
Recent developments in targeted mass spectrometry-based proteomics have provided new methodological solutions for accurate and quantitative analysis of proteins and their posttranslational control, which has significantly advanced our understanding of stress responses in different plant species. Instrumentation allowing high-resolution, accurate-mass (HR/AM) analysis has provided new acquisition strategies for targeted quantitative proteomic analysis by targeted selected ion monitoring (tSIM) and parallel reaction monitoring (PRM). Here we report a sensitive and accurate method for targeted analysis of protein phosphorylation by tSIM coupled to PRM (tSIM/PRM). The tSIM/PRM method takes advantage of HR/AM mass spectrometers and benefits from the combination of highly sensitive precursor ion quantification by tSIM and highly confident peptide identification by spectral library matching in PRM. The detailed protocol describes tSIM/PRM analysis of Arabidopsis thaliana foliar proteins, from the building of a spectral library to sample preparation, mass spectrometry, and data analysis, and provides a methodological approach for specifying the molecular mechanisms of interest.


Transient otoacoustic emissions in the detection of olivocochlear bundle maturation.
The medial olivocochlear bundle, forms a neural pathway connecting the superior olivary complex to the outer hair cells of mainly the contralateral cochlea. Although the biological significance of the bundle remains ambiguous, it is clear that activation of medial olivocochlear fibers alters cochlear output and this can be experimentally evident through a series of changes on otoacoustic emissions, called otoacoustic emission suppression. The aim of this study is to observe the maturation of the medial olivocochlear bundle by measuring the suppression effects on transient otoacoustic emissions. The study population consisted of 27 premature babies (53 ears) from the P&A Kyriakou Neonatal Intensive Care Unit (conceptional age: 31-36 weeks) and 43 fullterm babies (61 ears) (conceptional age: 37-42 weeks) from the same unit. The ILO-92 system is used to deliver both the linear clicks to the ear examined (producing the emissions) and the white noise to the contralateral ear. The mode used is based on the alternating on and off presence of the white noise in the contralateral ear. 12/53 (22%) ears of preterm babies presented suppression > or =1 dB. 32/61 (52.4%) ears of fullterm babies presented suppression > or =1 dB. The mean suppression for the ears of premature infants was 0.52 dB, (+/-0.1 S.E.M.). The mean suppression for the ears of fullterm infants was 0.90 dB, (+/-0.09 S.E.M.). At the second half of the time window, suppression of fullterms rises above 1 dB (a pattern similar to that of adults), whereas it remains below 1 dB for preterms. Suppression of otoacoustic emissions helps us to study the function of the medial olivocochlear bundle in different populations. It appears in premature babies but becomes stronger as the postconceptional age advances.


Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors.
LY2334737 is an oral gemcitabine prodrug. This Phase I study assessed the safety and tolerability of LY2334737 in Japanese patients with solid tumors and evaluated pharmacokinetics (PK), pharmacodynamics, and antitumor activity. Patients with advanced/metastatic solid tumors received escalating doses of LY2334737 once daily for 14 days, followed by a 7-day drug-free period. Cycles were repeated until discontinuation criteria were met. Of 13 patients treated, 3 received 20 mg/day, 6 received 30 mg/day, 4 received 40 mg/day. On the 40 mg dose, 3 patients experienced dose-limiting toxicities (DLTs): hepatic toxicities (e.g., Grade [G]3/4 transaminase and G1-3 bilirubin elevation) and G4 thrombocytopenia; all 3 showed features of disseminated intravascular coagulation. One additional DLT occurred on the 30 mg dose (G3 transaminase elevation). Exploratory pharmacogenetic analyses identified a genetic variation in the CES2 gene potentially associated with these DLTs. PK data showed no clear relationship between the AUC of gemcitabine and its incorporation into leukocyte DNA; 2 of the 3 DLT patients had high incorporation. Two patients (30 mg/day) achieved stable disease with progression-free survival lasting 135 and 155 days. LY2334737 was tolerated by Japanese patients up to 30 mg/day. The toxicities observed at the 40 mg dose may require the development of alternative dosing schedules.


The multifunctional role of transforming growth factor (TGF)-beta s on mammary epithelial cell biology.
The transforming growth factor-beta s are potent growth inhibitors of normal and transformed breast epithelial cells in culture. In vivo, these peptides modulate the development of the mouse mammary gland. Tissue-specific overexpression of mature TGF-beta 1 in transgenic mice results in mammary gland atrophy and prevention of carcinogen-induced breast tumorigenesis. However, the inhibitory effect of endogenous or exogenous TGF-beta s on established tumor cells is less clear. Several published circumstantial and more direct data argue that, in some cases, the tumor cell TGF-beta s may contribute to the maintenance and/or progression of tumor cells in an intact host by modulating their interaction with host factors. This differential role of the TGF-beta s on mammary cells as determined by their normal or transformed phenotype as well as the biological and clinical implications of these data are discussed.


Does contracting of health care in Afghanistan work? Public and service-users' perceptions and experience.
In rebuilding devastated health services, the government of Afghanistan has provided access to basic services mainly by contracting with non-government organisations (NGOs), and more recently the Strengthening Mechanism (SM) of contracting with Provincial Health Offices. Community-based information about the public's views and experience of health services is scarce. Field teams visited households in a stratified random sample of 30 communities in two districts in Kabul province, with health services mainly provided either by an NGO or through the SM and administered a questionnaire about household views, use, and experience of health services, including payments for services and corruption. They later discussed the findings with separate community focus groups of men and women. We calculated weighted frequencies of views and experience of services and multivariate analysis examined the related factors. The survey covered 3283 households including 2845 recent health service users. Some 42% of households in the SM district and 57% in the NGO district rated available health services as good. Some 63% of households in the SM district (adjacent to Kabul) and 93% in the NGO district ordinarily used government health facilities. Service users rated private facilities more positively than government facilities. Government service users were more satisfied in urban facilities, if the household head was not educated, if they had enough food in the last week, and if they waited less than 30 minutes. Many households were unwilling to comment on corruption in health services; 15% in the SM district and 26% in the NGO district reported having been asked for an unofficial payment. Despite a policy of free services, one in seven users paid for treatment in government facilities, and three in four paid for medicine outside the facilities. Focus groups confirmed people knew payments were unofficial; they were afraid to talk about corruption. Households used government health services but preferred private services. The experience of service users was similar in the SM and NGO districts. People made unofficial payments in government facilities, whether SM or NGO run. Tackling corruption in health services is an important part of anti-corruption measures in Afghanistan.


The prevalence of refractive errors in 5-15 year-old population of two underserved rural areas of Iran.
To determine the prevalence of hyperopia and myopia and their associations with age and gender in 5- to 15-year-old children in underserved rural areas in Iran. In this cross-sectional study, sampling was done using a multistage cluster sampling method from two underprivileged rural regions in Iran, and 3851 persons over 1 year old of age were invited to the study. After inviting the selected participants, examinations were conducted at a designated site in the selected villages. All participants underwent measurements of uncorrected and corrected visual acuity, manifest refraction, and a slit-lamp examination. Cycloplegic refraction was done by instilling cyclopentolate 1% eye drops in under 15-year-old participants. Of the 3851 selected persons, 3314 subjects participated (86.5%), and of these, 602 were in the 5-15 year age group. The prevalence of myopia and hyperopia in the studied children was 2.60% [95% confidence interval (CI): 1.10-4.10] and 4.00% (95% CI: 1.84-6.15), respectively. The prevalence of myopia in male and female children was 2.65% and 2.55%, respectively (P = 0.951). The prevalence of hyperopia in male and female children was 2.83% and 5.25%, respectively (P = 0.130). The prevalence of myopia in the villages of southwest and north was 2.42% and 3.09%, respectively (P = 0.618), and the prevalence of hyperopia was 4.71% and 2.10%, respectively (P = 0.0056). The present report is a brief description of the status of refractive errors in children residing in underprivileged villages of two rural districts in Iran. As presented, the prevalence of myopia is not high, although the prevalence of hyperopia is in the mid-range compared to previous studies.


Intraoperative Imaging for High-Grade Glioma Surgery.
This article discusses intraoperative imaging techniques used during high-grade glioma surgery. Gliomas can be difficult to differentiate from surrounding tissue during surgery. Intraoperative imaging helps to alleviate problems encountered during glioma surgery, such as brain shift and residual tumor. There are a variety of modalities available all of which aim to give the surgeon more information, address brain shift, identify residual tumor, and increase the extent of surgical resection. The article starts with a brief introduction followed by a review of with the latest advances in intraoperative ultrasound, intraoperative MRI, and intraoperative computed tomography.


Avatrombopag: A Review in Thrombocytopenia.
Avatrombopag (Doptelet®) is an orally administered second generation thrombopoietin receptor agonist (TPO-RA) approved for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory or have an unsatisfactory response to other treatments, as well as for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) scheduled to undergo an invasive procedure. In phase III studies, avatrombopag was associated with a significantly greater platelet response than placebo in patients with chronic ITP, and was superior to placebo in reducing the requirement for platelet transfusion or rescue procedures for bleeding caused by surgery in patients with CLD with a platelet count < 50 × 109/L at baseline. Longer term data indicate that avatrombopag is associated with high durable response rates in ITP and may have corticosteroid-sparing effects. The drug was generally well tolerated in both indications. Avatrombopag thus represents a convenient and effective second-line treatment for patients with chronic ITP and can prevent bleeding events in patients with CLD scheduled to undergo a procedure, offering a useful alternative to other available treatments in both indications.


The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18,628 individuals.
Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case-control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19-1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63-3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47-2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12-1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.


The relationship between the Gabor elementary function and a stochastic model of the inter-spike interval distribution in the responses of visual cortex neurons.
In a previously reported study (Berger et al. 1990) we analyzed distributions of interspike intervals recorded extracellularly from cat visual cortex under four stimulus conditions. Stimuli were gratings differing in orientation and spatial frequency. The probability density function of first passage time for a random walk with drift process, which is defined by its barrier height and drift coefficient, was used to characterize the generating process of axonal discharge under resting and stimulus conditions. Drift coefficient and barrier height were derived from the sample mean and standard deviation of the measured inter-spike intervals. For cells with simple receptive fields, variations in spatial frequency produced changes only in drift coefficient. Variations in barrier height were produced only by changes in orientation of the stimulus. Currently, the method used to analyze these data was implemented in a simulation which displayed the relationship between the interval distribution of impulses, the random walk which represents the time series characteristic of the spike train model and the Gabor filter function which represents the geometry of the receptive field process.


Aspirin and other antiplatelet drugs in the prophylaxis of thrombosis.
Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. After a myocardial infarction it reduces the risk of death by about 10% and of coronary incidence (coronary death or definite myocardial infarction) by about 25%. These effects appear to be additive with those of beta-blocking drugs. Aspirin also reduces the risk of occlusion of aortocoronary saphenous vein grafts by about half. In transient cerebral ischaemia, aspirin may reduce the risk of stroke and death by 50%. In most clinical trials to date the daily dose of aspirin ranges from 325 mg to 1400 mg. Interest in very low doses of aspirin (less than 60 mg daily) is considerable but has yet to be translated into proven clinical benefit. Dipyridamole has not been shown to be effective as an antithrombotic when used alone. Its antiplatelet action ex vivo may be enhanced by combination with aspirin but clinical trials have shown relatively little advantage of the combination over aspirin alone. Sulphinpyrazone has not become established as a first line antithrombotic drug. Epoprostenol is useful in extracorporeal circulations to prevent platelet consumption and possibly in severe inoperable peripheral vascular disease.


The effect of ethanol on the habit and in vitro aerodynamic results of dry powder inhalation formulations containing ciprofloxacin hydrochloride.
In the case of dry powder inhalation systems (DPIs), the development of carrier-free formulations has gained increased attention. Thereby, spray-drying is a promising technology and is widely used to produce carrier-free DPIs. Numerous works have been published about the co-spray-drying of active ingredients with various solid excipients and their effect on the physicochemical characteristics and aerodynamic properties of the formulations. However, only a few studies have been reported about the role of the solvents used in the stock solutions of spray-dried formulations. In the present work, DPI microcomposites containing ciprofloxacin hydrochloride were prepared by spray-drying in the presence of different ethanol concentrations. The work expresses the roughness, depth and width of the dimples for particle size as a novel calculation possibility, and as a correlation between the MMAD/D0.5 ratio and correlating it with cohesion work, these new terms and correlations have not been published - to the best of our knowledge - which has resulted in gap-filling findings. As a result, different proportions of solvent mixtures could be interpreted and placed in a new perspective, in which the influence of different concentrations of ethanol on the habit of the DPI formulations, and thus on in vitro aerodynamic results. Based on these, it became clear why we obtained the best in vitro aerodynamic results for DPI formulation containing 30% ethanol in the stock solution.


New alternatively spliced variants of calmodulin-dependent protein kinase II from rabbit liver.
Polymerase chain reaction analysis revealed four alternatively spliced variants of each of the gamma and delta isoforms of calmodulin-dependent protein kinase II (CaM-kinase II) in rabbit liver. Among the four variants of the gamma isoform, two were novel ones, designated as CaM-kinase II gamma-H and gamma-I. The gamma-I variant possessed both of the two deletable exons; D2a and D2b, which had never been found together in any variant. Sequence analysis of the gamma-I indicated that the D2a was upstream of the D2b and that they were contiguous with each other in the gamma-I. Among the four variants of the delta isoform, two were also novel ones, designated as CaM-kinase II delta-11 and delta-12, and the other two were the already-reported ones, delta-2 and delta-6. The delta-11 and delta-12 were identical to the delta-2 and delta-6, respectively, except that three bases (CAG) located at a splicing junction was deleted in the delta-11 and delta-12, suggesting two splicing sites of a single intron. Thus, the diverse splicing patterns may produce many more variants than those so far considered.


In-situ glyoxalization during biosynthesis of bacterial cellulose.
A novel method to synthesize highly crosslinked bacterial cellulose (BC) is reported. The glyoxalization is started in-situ, in the culture medium during biosynthesis of cellulose by Gluconacetobacter medellensis bacteria. Strong crosslinked networks were formed in the contact areas between extruded cellulose ribbons by reaction with the glyoxal precursors. The crystalline structure of cellulose was preserved while the acidic component of the surface energy was reduced. As a consequence, its predominant acidic character and the relative contribution of the dispersive component increased, endowing the BC network with a higher hydrophobicity. This route for in-situ crosslinking is expected to facilitate other modifications upon biosynthesis of cellulose ribbons by microorganisms and to engineer the strength and surface energy of their networks.


Longevity and failure load of ceramic veneers with different preparation designs after exposure to masticatory simulation.
Laminate veneers are widely used in the management of unesthetic anterior teeth. However, limited information is available regarding the influence of preparation design on longevity of ceramic veneers. This study evaluated the influence of preparation design on longevity and failure load of ceramic veneers bonded to human maxillary central incisors after cyclic loading and thermal cycling in a dual-axis masticatory simulator. Sixty-four caries-free maxillary central incisors were divided into 4 groups (n = 16). The control group remained unprepared (NP). For Group WP, a window preparation was made. Specimens in Group IOP were prepared with an incisal overlap of 2 mm without palatal chamfer. For Group CVP, specimens were prepared with a complete-veneer design of 3-mm incisal reduction and 2-mm palatal extension. Forty-eight IPS Empress 1 ceramic veneers were bonded adhesively with dual-polymerizing composite (Variolink II). All specimens were subjected to cyclic mechanical loading (1.2 million cycles, cycle frequency 1.3 Hz, invariable palatal load 49 N) and thermal cycling (5 degrees C-55 degrees C, dwell time 60 seconds, 5500 cycles) in a masticatory simulator. Failure was defined by bulk fracture of a specimen. Subcritical crack patterns were observed. Surviving specimens were loaded in a universal testing machine until fracture. The failure-load values (N) (1.5 mm/min crosshead speed) were automatically recorded by controlling software. Statistical analysis of data was performed by Kruskal-Wallis analysis of variance (alpha = .05) and pairwise Wilcoxon rank sum tests (alpha = .05). Three specimens from group NP, 1 specimen each from the WP and CVP groups, and 2 specimens from group IOP fractured during fatigue. After 1.2 million cycles, the highest crack rates were observed for complete veneers and originated in the palatal concavity extending to the facial surface. The median (interquartile range = x .25 - x .75 ) failure loads (N) were as follows: NP 713.3 (404.4-777.1), WP 549.5 (477.5-597.7), IOP 695.3 (400.0-804.6), and CVP 519.2 (406.1-732.9). No significant differences in longevity and failure load were demonstrated between natural teeth and teeth restored with ceramic veneers ( P = .555). Maxillary teeth restored with the 3 types of IPS Empress 1 veneers showed fracture resistance similar to that of unprepared incisors ( P = .555).


Correlations of natural radionuclides in soil with those in sediment from the Danube and nearby irrigation channels.
The correlation between activity concentrations of some natural radionuclides ((238)U, (226)Ra, (232)Th, (40)K) measured in soil and in sediment taken from the Danube River and nearby irrigation channels was studied. The soil samples were collected from the northern part of Serbia and the sediment from the Serbian part of the Danube River and from the surrounding irrigation channels. The correlation between (238)U and other natural radionuclides in irrigation channel sediments was not as good as in the Danube. One of the possible explanations for this weak correlation can be the different chemical dynamics of (238)U in the irrigation channel sediment or changes of the (238)U activity concentration in irrigation channel sediment due to some human activities. The evaluation of ratios of activity concentrations of some natural radionuclides could be a more sensitive method for the determination of contaminant, rather than the straightforward analysis of activity concentrations.


Parkinson's disease of post-encephalitic type following general paresis--an autopsied case.
A clinico-pathological report is given of a case of Parkinson's disease following a general paresis. A 66-year-old male, with no previous history of febrile disease or viral encephalitides, developed a dementing illness. The general paresis was diagnosed from serological studies at the age of 45. He underwent a series of penicillin plus fever therapies as treatment for neurosyphilis. He also developed generalized rigidity and slow mobility 12 years after the diagnosis of general paresis. An anti-Parkinson drug was given. Finally he fell in a state of muteness and became bedridden. He had been hospitalized for 21 years and died from bronchopneumonia. The pathological findings were strikingly similar to post-encephalitic parkinsonism in addition to a healed state of general paresis. They consisted of a widespread nerve cells loss, gliosis and the presence of Alzheimer's neurofibrillary tangles in the substantia nigra. In the cerebral cortex, a diffuse loss of nerve cells and the presence of a weak positive iron reaction were observed. The coexistence of general paresis and post-encephalitic parkinsonism is unusual and the authors discussed the etiological relationship between the two different conditions.


Retention of oxidized glutathione by isolated rat liver mitochondria during hydroperoxide treatment.
The addition of tert-butyl hydroperoxide (t-BuOOH) to isolated mitochondria resulted in oxidation of approximately 80% of the mitochondrial reduced glutathione (GSH) independently of the dose of t-BuOOH (1-5 mM). Concomitant with the oxidation of GSH inside the mitochondria was the formation of GSH-protein mixed disulfides (protein-SSG), with approximately 1% of the mitochondrial protein thiols involved. A dose-dependent rate of GSH recovery was observed, via the reduction of oxidized GSH (GSSG) and a slower reduction of protein-SSG. Although t-BuOOH administration affected the respiratory control ratio, the mitochondria remained coupled and loss of the matrix enzyme, citrate synthase, was not increased over the control and was less than 3% over 60 min. A slow loss of GSH out of the coupled non-treated mitochondria was not increased by t-BuOOH treatment, in fact, a dose-dependent drop of GSH levels occurred in the medium. However, no GSSG was found outside the mitochondria, indicating the necessary involvement of enzymes in the t-BuOOH-induced conversion of GSH to GSSG. The absence of GSSG in the medium also suggests that, unlike the plasma membrane, the mitochondrial membranes do not have the ability to export GSSG as a response to oxidative stress. Our results demonstrate the inability of mitochondria to export GSSG during oxidative stress and may explain the protective role of mitochondrial GSH in cytotoxicity.


Bacterial community dynamics within an aerobic granular sludge reactor treating wastewater loaded with pharmaceuticals.
Pharmaceuticals are micropollutants often present in wastewater treatment systems. In this study, the potential impact of such micropollutants on the bacterial population within aerobic granular sludge (AGS) bioreactor was investigated. The AGS bacterial community structure and composition were accessed combining DGGE fingerprinting and barcoded pyrosequencing analysis. Both revealed the existence of a dynamic bacterial community, independently of the pharmaceuticals presence. The AGS microbiome at both phylum and class levels varied over time and, after stopping pharmaceuticals feeding, the bacterial community did not return to its initial composition. Nevertheless, most of the assigned OTUs were present throughout the different operational phases. This core microbiome, represented by over 72% of the total sequences in each phase, probably played an important role in biological removal processes, avoiding their failure during the disturbance period. Quantitative-PCR revealed that pharmaceuticals load led to gradual changes on the abundance of ammonia-oxidizing bacteria (AOB), nitrite-oxidizing bacteria (NOB) and polyphosphate-accumulating organisms (PAO) but their persistence during that phase demonstrated the resilience of such bacterial groups. AGS microbiome changed over time but a core community was maintained, probably ensuring the accomplishment of the main biological removal processes.


An optimized spectrophotometric assay reveals increased activity of enzymes involved in 2-arachidonoyl glycerol turnover in the cerebral cortex of a rat model of Alzheimer's disease.
The endocannabinoid system is implicated in a plethora of neuropsychiatric disorders. However, it is technically challenging to assess the turnover of 2-arachidonoyl glycerol (2-AG), the principal endocannabinoid molecule in the brain. Two recent studies showed that diacylglycerol lipase α (DAGLα), an enzyme chiefly responsible for the cerebral production of 2-AG, also accepts the surrogate chromogenic substrate 4-nitrophenyl butyrate (4-NPB). Here, we aimed to optimize this spectrophotometric assay for ex vivo brain tissue, in particular, rat cerebrocortical homogenates, to measure the activity of the major enzymes responsible for the production and degradation of 2-AG. The initial velocity of 4-NPB hydrolysis was dependent on protein, substrate, and Ca2+ concentrations, and was sensitive to the non-selective serine hydrolase inhibitor, methoxy arachidonyl fluorophosphonate, the DAGLα inhibitors, OMDM188, tetrahydrolipstatin, and RHC80267, as well as the monoacylglycerol lipase (MAGL) inhibitor, JZL184, respectively. Next, we tested the usefulness of this assay in ex vivo brain tissue of rat models of human health conditions known to affect cerebrocortical 2-AG production, i.e. pathological stress and sporadic Alzheimer's disease (AD). In rats submitted to chronic restraint stress, cortical CB1 R density was significantly decreased, as assessed with radioligand binding. Nevertheless, 4-NPB hydrolysis remained at control levels. However, in rats 4 weeks after intracerebroventricular injection with streptozotocin - an established model of sporadic AD -, both CB1 R levels and 4-NPB hydrolysis and its DAGL- and MAGL-dependent fractions were significantly increased. Altogether, we optimized a simple complementary ex vivo technique for the quantification of DAGL and MAGL activity in brain samples.


One simple claudication question as first step in Peripheral Arterial Disease (PAD) screening: A meta-analysis of the association with reduced Ankle Brachial Index (ABI) in 27,945 subjects.
A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of the studies were pooled in a random effect meta-analysis, which included data from 27,945 individuals (14,052 women, age range 20-84 years). Meta-analysis revealed a significant negative association between claudication and ABI, which was stronger in men (β = -0.07; 95%CI -0.10, -0.04) than in women (β = -0.02; 95%CI -0.02, -0.01). Likewise, the presence of claudication symptoms was related to an increased odds of a decreased ABI in both men (Odds ratio = 5.40; 95%CI 4.20, 6.96) and women (Odds ratio = 1.99; 95%CI 1.58, 2.51). Asking only one question about claudication was able to identify many individuals with a high likelihood of a reduced ABI with markedly higher sensitivity and only slightly reduced specificity compared to more complex questionnaires. At least in men, this question should be established as first screening step.


The combined anterolateral thigh-Partial iliac crest minihybrid free flap for mandibular reconstruction.
Tumors of the oral cavity often require extensive resections leading to significant hard and soft tissue defects. Microvascular free flaps, consisting of both hard and soft tissue, are often required in reconstructions. Hybrid flaps, composed of two different joint free flaps, offer potential alternatives for head and neck reconstruction. This report presents our results with a modified hybrid ALT/DCIA, that is, minihybrid free flap (MH-flap) composed of the anterolateral thigh (ALT) and a partial inner lamina iliac crest only (partial DCIA) for reconstruction of the mandibular region. Eight patients underwent oral cancer reconstruction of the mandible with the MH-flap. The MH-flap was harvested sparing the outer crest and lamina of crista, and its pedicle was combined to the distal pedicle of ALT. Clinical data and postoperative complications were analyzed. The mean length of the osseous graft was 64 mm (range 54-78 mm). None of the patients had complications requiring surgical intervention. No donor site complications were observed. The overall survival rate was 100%. The mean length of follow-up was 16 months (range 7-30 months). According to our results, the ALT-partial DCIA MH-flap has postoperative outcomes comparable to those of the fibular flap. The flap is a good option with excellent bone properties for reconstruction of limited mandibular defects not suitable for fibular or scapular reconstruction.


[Physico-chemical stability and sterility of non-opioid analgesics in solution].
The combination of non-opioid analgesic drugs (P: paracetamol, K: ketoprofen and N: nefopam) is currently recommended for postoperative pain control. In practice, these analgesics are often administered in the same solution. We investigated the chemical stability and sterility of three mixtures of analgesics (P+K, P+N and K+N). For each mixture, concentrations of active principles were measured using high-performance liquid chromatography over 24 hours. These mixtures were cultured for microbiological colonization. Our study demonstrated chemical and bacteriologic stability of these three mixtures over a 24-hour period. The results allow the use of P+K, P+N and K+N in the same ready to use solution.


Mitotic ER Exit Site Disassembly and Reassembly Are Regulated by the Phosphorylation Status of TANGO1.
Golgi fragmentation and ER exit site disassembly are considered to be the leading causes of the mitotic block of secretion from the ER. Although the mechanisms of Golgi fragmentation have been extensively characterized, ER exit block early in mitosis is not well understood. We previously demonstrated that TANGO1 organizes ER exit sites by directly interacting with Sec16. In this study, we identified TANGO1 as a regulator of ER exit site disassembly during mitosis. TANGO1 phosphorylation was observed to be coordinately regulated by a kinase (CK1) and a phosphatase (PP1). CK1-mediated TANGO1 phosphorylation reduces binding to Sec16, leading to the disassembly of ER exit sites. CK1 constantly phosphorylates TANGO1, whereas PP1-mediated dephosphorylation of TANGO1 decreases during mitosis. Thus, the phosphorylation status of TANGO1, which is controlled by balanced activities of the kinase CK1 and the phosphatase PP1, regulates the organization of ER exit sites during the cell cycle.


The effect of vaccines based on ovalbumin coupled to gas-filled microbubbles for reducing infection by ovalbumin-expressing Listeria monocytogenes.
Gas-filled microbubbles (MB) are a very promising alternative to the currently evaluated lipid- or polymer-based particulate Ag delivery systems. We recently demonstrated the ability of MB to deliver associated Ag to DC, to activate them and thereby induce both humoral and cellular immune responses. We now extended the characterization of MB as antigen-delivery system by appraising the efficiency of MB-associated ovalbumin (OVA-MB) at protecting mice against pathogen infection. Ultrasound-mediated imaging demonstrated that the administration of OVA via MB generates a depot at the injection site that lasts for several hours. We found that OVA-MB injected subcutaneously is far more effective at inducing specific Ab and T cell immunity than immunization with free OVA. Moreover, a covalent link between MB and OVA causes a stronger bias towards a Th1-type of immune response than adsorption of the Ag or its covalent link to liposomes of the same lipid composition. Finally, vaccination of mice with OVA-MB partially protects against a systemic infection with OVA-expressing Listeria monocytogenes. The vaccine induces specific effector CD8 T cell responses capable of decreasing more than 100 fold the bacterial load. MB thus represent a potent Ag delivery system for vaccination against intracellular infectious agents.


The economic burden of road traffic injuries until one-year after hospitalization: A survey study.
Road Traffic Injuries (RTIs) are one of the most crucial and challenging public health problems in low and middle income countries. Despite continuous efforts to estimate both personal and societal costs of RTIs however, their long-term effects have remained marginal. The current study aimed to explore the economic burden of RTIs until one year after the victim's hospitalization. The study included a total of 1150 RTI victims, who were admitted to two trauma-referral hospitals during 2016. Data on direct medical costs, direct non-medical costs and indirect costs were gathered for each study sample via hospital records and phone surveys. Direct and indirect costs from a social perspective were estimated based on Micro Costing Approach followed by the Human Capital Approach. Also, the explanatory variables affecting the costs of RTIs were identified using the liner regression model. The average amounts of direct (medical, non-medical), indirect, and total costs of RTI were estimated as 2,908 US$ (1,591 US$, 1,316 US$), 5,790 US$, and 8,701 US$ respectively. Also, several variables were significantly affecting the costs of RTIs including age, marital status, employment status, severity of injury, receiving physiotherapy care, victim's vehicle type in crash, crash time and location. Findings suggest that RTIs are considered as an enormous burden on Iranian GDP per capita and health expenditure per capita occupying 167% and 347% respectively. This enormous economic burden caused by RTIs requires more policy regulations and prevention programs to decrease RTIs.


CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist, prevents hypertension and cardiorenal injury in Dahl salt-sensitive hypertensive rats.
The present study was designed to evaluate the antihypertensive and cardiorenal protective effects of CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist, in Dahl salt-sensitive hypertensive rats (DS rats), and to compare the effects with spironolactone and eplerenone. DS rats were fed a control diet (0.3% NaCl) or high salt diet (8% NaCl) from 7 weeks of age. CS-3150 (0.25-2mg/kg), spironolactone (10-100mg/kg) or eplerenone (10-100mg/kg) were orally administered once a day to DS rats fed a high salt diet for 7 weeks. The high salt diet significantly increased systolic blood pressure, which was prevented by treatment with CS-3150 in a dose-dependent manner with no hyperkalemia (>5.5mEq/L). The antihypertensive effect of CS-3150 (0.5mg/kg) was equivalent to that of spironolactone (100mg/kg) and eplerenone (100mg/kg). CS-3150 also suppressed proteinuria and renal hypertrophy induced by the high salt diet. Histopathological examination of kidneys showed that CS-3150 markedly ameliorated glomerulosclerosis, tubular injury and tubulointerstitial fibrosis. In addition, CS-3150 inhibited left ventricular hypertrophy and elevation of plasma brain natriuretic peptide level. In contrast, the cardiorenal protective effects of spironolactone or eplerenone were partial, and the dose-dependency was not clear, especially in eplerenone-treated rats. These results indicate that chronic treatment with CS-3150 exerts antihypertensive and cardiorenal protective effects in a DS hypertensive rat model, and its potency is much superior to that of spironolactone or eplerenone. Thus, CS-3150 could be a promising agent for the treatment of hypertension and cardiorenal disorders.


Design, Synthesis and Biological Activity of Some 4, 5-Disubstituted-2, 4- Dihydro-3H-1, 2, 4- Triazole-3-Thione Derivatives.
In the present study, 4, 5-disubstituted triazol-3-thione derivatives were synthesized and evaluated for anticonvulsant activity along with neurotoxicity determination. The synthesized compounds were characterized using FTIR, 1H-NMR and MS. The anticonvulsant activity was assessed by Maximal Electroshock (MES) test and subcutaneous Pentylenetetrazole (scPTZ) tests and neurotoxicity was assessed by rotarod test. Docking was also performed to study the interactions of compounds with LYS329 residue of gamma amino butyric acid aminotransferase (GABA-AT) using Autodock 4.2 software. The compounds 7a and 9a with significant pharmacological activity were also found to interact with LYS329 residue of GABA-AT by H-bond with a docking score of -5.92 kcal/mol (Ki = 41.99 μM) and -5.87 kcal/mol (Ki = 49.83 μM) respectively. Most of the compounds were found to be active in MES test but only seven showed protection in scPTZ test.


Deciphering the Potential Pharmaceutical Mechanism of Chinese Traditional Medicine (Gui-Zhi-Shao-Yao-Zhi-Mu) on Rheumatoid Arthritis.
Gui-Zhi-Shao-Yao-Zhi-Mu (GSZ) decoction is a Traditional Chinese Medicine (TCM) formula commonly used for the treatment of Rheumatoid Arthritis (RA). The therapeutic effect of GSZ for RA treatment is supported by our clinical retrospective study. To uncover the potential mechanism underlying GSZ formula, we identified 1,327 targets of 673 compounds from 9 herbs that involve in Fc epsilon RI signaling pathway and regulation of immunoglobulin production. Comparison between formula targets with 79 RA drug targets and 675 RA disease genes showed that formula targets covered 31.6% RA drug targets and 19.9% RA disease genes. Formula specific targets presented expression patterns highly similar to the disease genes and drug targets based on the expression profiles of RA samples. Investigation of 10 inferred gene clusters from expression profiles with a target association network revealed that formula specific targets directly or indirectly interacted with disease genes that were essential for immune related biological processes (e.g. inflammatory responses, treatment response of rheumatoid arthritis, etc.). Our result indicated that GSZ disrupted the RA disease dysfunction modules and restored homeostasis in the human body. The systemic approach to infer therapeutic mechanisms of GSZ for RA treatment provides a new insight in the understanding of this TCM formula.


Assessment of Free-Living Cadence Using ActiGraph Accelerometers Between Individuals With and Without Anterior Cruciate Ligament Reconstruction.
Anterior cruciate ligament reconstruction (ACLR) and gait speed are risk factors for developing knee osteoarthritis (OA). Measuring minute-level cadence during free-living activities may aid in identifying individuals at elevated risk of developing slow habitual gait speed and, in the long term, OA. To assess differences in peak 1-minute cadence and weekly time in different cadence intensities between individuals with and without ACLR. Cross-sectional study. Short-term, free-living conditions. A total of 57 participants with ACLR (34 women, 23 men; age = 20.9 ± 3.2 years, time since surgery = 28.7 ± 17.7 months) and 42 healthy control participants (22 women, 20 men; age = 20.7 ± 1.7 years). Each participant wore a physical activity monitor for 7 days. Data were collected at 30 Hz, processed in 60-second epochs, and included in the analyses if the activity monitor was worn for at least 10 hours per day over 4 days. Mean daily steps, peak 1-minute cadence, and weekly minutes spent at 60 to 79 (slow walking), 80 to 99 (medium walking), 100 to 119 (brisk walking), ≥100 (moderate- to vigorous-intensity ambulation), and ≥130 (vigorous-intensity ambulation) steps per minute were calculated. One-way analyses of covariance were conducted to determine differences between groups, controlling for height and activity-monitor wear time. Those with ACLR took fewer daily steps (8422 ± 2663 versus 10 033 ± 3046 steps; P = .005) and spent fewer weekly minutes in moderate- to vigorous-intensity cadence (175.8 ± 116.5 minutes versus 218.5 ± 137.1 minutes; P = .048) than participants without ACLR. We observed no differences in minutes spent at slow (ACLR = 77.4 ± 40.5 minutes versus control = 83.9 ± 34.3 minutes; P = .88), medium (ACLR = 71.6 ± 40.2 minutes versus control = 82.9 ± 46.8 minutes; P = .56), brisk (ACLR = 115.3 ± 70.3 minutes versus control = 138.3 ± 73.3 minutes; P = .18), or vigorous-intensity (ACLR = 24.3 ± 36.5 minutes versus control = 38.1 ± 60.9 minutes; P = .10) cadences per week. Participants with ACLR walked approximately 40 fewer minutes per week in moderate- to vigorous-intensity cadence than participants without ACLR. Increasing the time spent at cadence ≥100 steps per minute and overall volume of physical activity may be useful as interventional targets to help reduce the risk of early development of OA after ACLR.


Cooling and stabilization by collisions in a mixed ion-atom system.
In mixed systems of trapped ions and cold atoms, the ions and atoms can coexist at different temperatures. This is primarily due to their different trapping and cooling mechanisms. The key questions of how ions can cool collisionally with cold atoms and whether the combined system allows stable coexistence, need to be answered. Here we experimentally demonstrate that rubidium ions cool in contact with magneto-optically trapped rubidium atoms, contrary to the general experimental expectation of ion heating. The cooling process is explained theoretically and substantiated with numerical simulations, which include resonant charge exchange collisions. The mechanism of single collision swap cooling of ions with atoms is discussed. Finally, it is experimentally and numerically demonstrated that the combined ion-atom system is intrinsically stable, which is critical for future cold chemistry experiments with such systems.


Flexible realistic simulation of seizure occurrence recapitulating statistical properties of seizure diaries.
A realistic seizure diary simulator is currently unavailable for many research needs, including clinical trial analysis and evaluation of seizure detection and seizure-forecasting tools. In recent years, important statistical features of seizure diaries have been characterized. These include (1) heterogeneity of individual seizure frequencies, (2) the relation between average seizure rate and standard deviation, (3) multiple risk cycles, (4) seizure clusters, and (5) limitations on inter-seizure intervals. The present study unifies these features into a single model. Our approach, Cyclic Heterogeneous Overdispersed Clustered Open-source L-relationship Adjustable Temporally limited E-diary Simulator (CHOCOLATES) is based on a hierarchical model centered on a gamma Poisson generator with several modifiers. This model accounts for the aforementioned statistical properties. The model was validated by simulating 10 000 randomized clinical trials (RCTs) of medication to compare with 23 historical RCTs. Metrics of 50% responder rate (RR50) and median percent change (MPC) were evaluated. We also used CHOCOLATES as input to a seizure-forecasting tool to test the flexibility of the model. We examined the area under the receiver-operating characteristic (ROC) curve (AUC) for test data with and without cycles and clusters. The model recapitulated typical findings in 23 historical RCTs without the necessity of introducing an additional "placebo effect." The model produced the following RR50 values: placebo: 17 ± 4%; drug 38 ± 5%; and the following MPC values: placebo: 13 ± 6%; drug 40 ± 4%. These values are similar to historical data: for RR50: placebo, 21 ± 10%, drug: 43 ± 13%; and for MPC: placebo: 17 ± 10%, drug: 41 ± 11%. The seizure forecasts achieved an AUC of 0.68 with cycles and clusters, whereas without them the AUC was 0.51. CHOCOLATES represents the most realistic seizure occurrence simulator to date, based on observations from thousands of patients in different contexts. This tool is open source and flexible, and can be used for many applications, including clinical trial simulation and testing of seizure-forecasting tools.


Root canal morphology and bifurcating/merging sites of permanent mandibular incisors in 9- to 12-year-old children: An in-vivo 3D visualization analysis in China.
This retrospective study aims to analyze the root canal morphology of permanent mandibular incisors and the bifurcating/merging sites of root canal systems in children aged 9-12 in a Chinese subpopulation.Design Cone-beam computed tomography scans of 976 healthy, untreated and fully developed mandibular incisors were collected. Root canal morphology was identified by Vertucci's classification. Combined three-dimensional reconstruction and visualization techniques were used to locate bifurcating/merging sites in root canals. Vertucci I was the most common classification of mandibular central incisors (42.3%) while Vertucci III was most common in mandibular lateral incisors (37.9%). Females more frequently showed Vertucci I classification (49.5% central incisors and 36.7% lateral incisors) while Vertucci III was most common among males (44.5% central incisors and 41.0% lateral incisors). The difference in canal classification by sex was statistically significant (p < 0.05). 58.7% of Vertucci V canals bifurcated in the apical third (AT) in central incisors, while 69.5% bifurcated in the middle third (MT) in lateral incisors. Bifurcating and merging in AT (44.3%) was the most common style of Vertucci III canals in central incisors, while bifurcating in MT and merging in AT (53.8%) was the most common in lateral incisors. The root canal morphology of mandibular incisors in children aged 9-12 was different from that reported in previous studies on adults, and closely related to sex. Males had significantly greater canal variability than females. Lateral incisors had greater canal variability than central incisors. The bifurcating/merging sites were closely related to tooth type.


Clinical factors affecting endometrial receptiveness in oocyte donation cycles.
To provide a summary of the actual knowledge about the clinical factors affecting the oocyte recipient (other than those associated with uterine cavity abnormalities) on the outcome of oocyte donation cycles. Review of the literature. Information regarding the association between age, body mass index (BMI), endometrial priming, tobacco consumption, hydrosalpinx, and endometriosis/adenomyosis in oocyte recipients and the results of oocyte donation cycles. Recipient age and the presence of hydrosalpinx are clearly associated with a poorer outcome in oocyte donation cycles. The negative impact of tobacco consumption has recently been confirmed. The exact relevance of an elevated BMI is under debate but it is likely that it determines a lower ongoing pregnancy rate (PR). Endometriosis may be significant for endometrial receptiveness in the context of a natural cycle, but no negative impact is detected when standard endometrial priming protocols are used in oocyte donation. The same may be true for adenomyosis, although its relevance to endometrial receptiveness is less clear. Accumulated knowledge in the field of oocyte donation has led to the recognition of clinical variables that affect cycle outcome by impairing endometrial receptiveness. Many studies are being carried out on endometrial molecular and gene expression changes taking place in these circumstances. In the near future a comprehensive understanding of these processes should be achieved, from a genetic, molecular, and clinical perspective. These advances in the collective knowledge will lead to an improvement in the diagnosis and treatment of infertile patients.


Involuntary rest pauses (irps) in schizophrenics and normals.
Normal and schizophrenic Ss (N=24 each) performed a simple tapping task. The prediction that more involuntary rest pauses would be produced by schizophrenics than by normals was borne out. A discussion is given of the relation of these results to the interpretation of schizophrenia in terms of "arousal".


Fibular strut allograft influences reduction and outcomes after locking plate fixation of comminuted proximal humeral fractures in elderly patients: a retrospective study.
Proximal humeral fractures (PHFs) are the third most commonly occurring fractures in elderly patients. Most of these fractures can be treated with conservative methods, but the optimal surgical treatment strategy for unstable fractures in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes between locking compression plate (LCP) fixation and LCP fixation with fibular allograft implantation for the treatment of comminuted PHFs. We retrospectively reviewed 60 patients (mean age, 72.75 years) with closed 3- or 4-part fractures, and a minimum of 2 years of follow-up. Fracture reduction was quantitatively determined by humeral head height (HHH) and neck-shaft angle (NSA). The clinical outcome was evaluated by Constant-Murley score (CMS) and American Shoulder and Elbow Surgeons (ASES) score. The average radiological changes were higher in the LCP group than in the locking plate with fibular allograft group (HHH of 4.16 mm vs 1.18 mm [p < 0.001] and NSA of 9.94° versus 3.12° [p < 0.001]) . The final average outcome scores were lower in the LCP group than in the FA group (CMS of 73.00 vs 78.96 [p = 0.024] and ASES score of 72.80 vs 78.64 [p = 0.022]). The FA group showed better forward elevation (p = 0.010) and abduction (p = 0.002); however, no significant differences were observed for shoulder external rotation or internal rotation. The number of complications was higher in the LCP group (28.57%) than in the FA group (1.2%) (p < 0.001). For comminuted PHFs in elderly patients, LCP fixation combined with a fibular allograft is reasonable option to ensure satisfactory radiological and clinical outcomes. ZDYJLY(2018)New-9 . Name of registry: IEC for clinical Research of Zhongda Hospital, Affiliated to Southeast University. Date of registration: 2018-05-17.


Molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae isolates.
The emergence and transmission of tigecycline- and carbapenem-resistant Klebsiella pneumoniae (TCRKP) have become a major concern to public health globally. Here, we investigated the molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistant K pneumoniae (CRKP) isolates. Forty-five non-duplicate CRKP isolates were collected from January 2017 to June 2019. We performed antimicrobial susceptibility tests, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). PCR and DNA sequencing were performed for the detection and mutation analysis of acrR, oqxR, ramR, rpsJ, tet(A), and tet(X) genes, which are related to tigecycline resistance. The expression levels of efflux pump genes acrB and oqxB and their regulator genes rarA, ramA, soxS, and marA were assessed by quantitative real-time PCR. The resistance rate to tigecycline in CRKP isolates was 37.8% (17/45). K pneumoniae ST307 was a predominant clone type (70.6%, 12/17) among the TCRKP isolates. The expression levels of acrB (P < .001) and marA (P = .009) were significantly higher in the tigecycline-resistant group than in the tigecycline-intermediate and tigecycline-susceptible groups. Increased expression of acrB was associated with marA expression (r = 0.59, P = .013). We found that the activated MarA-induced overexpression of AcrAB efflux pump plays an important role in the emergence of tigecycline resistance in CRKP isolates.


[Sociology - Corona - CritiqueSociologie - coronavirus - critique].
The COVID-19 pandemic does not herald a new social era. Rather, the mechanisms of dealing with the pandemic, as far as they can be identified at this point, bear testimony to the structural socio-economic and socio-political crisis that must be regarded as the signature of democratic capitalism. Nor should the prevailing crisis management be misunderstood as a "politics of life" which (at least temporarily) suspends the capitalist logic of accumulation and of profit: as it is only certain lives that the governments of the democratic-capitalist industrialized countries are committed to saving and protecting. This means that any adoption of the life-coaching semantics of "crisis as an opportunity" should be treated with caution. However, for sociology itself the current circumstances could indeed offer an opportunity: that is, if it would finally stop denying that its own practice is inextricably enmeshed in (trans-)formative social processes and is never unideological, nor value-free, nor politically neutral.


Principles for coding associative memories in a compact neural network.
A major goal in neuroscience is to elucidate the principles by which memories are stored in a neural network. Here, we have systematically studied how four types of associative memories (short- and long-term memories, each as positive and negative associations) are encoded within the compact neural network of Caenorhabditis elegans worms. Interestingly, sensory neurons were primarily involved in coding short-term, but not long-term, memories, and individual sensory neurons could be assigned to coding either the conditioned stimulus or the experience valence (or both). Moreover, when considering the collective activity of the sensory neurons, the specific training experiences could be decoded. Interneurons integrated the modulated sensory inputs and a simple linear combination model identified the experience-specific modulated communication routes. The widely distributed memory suggests that integrated network plasticity, rather than changes to individual neurons, underlies the fine behavioral plasticity. This comprehensive study reveals basic memory-coding principles and highlights the central roles of sensory neurons in memory formation.


College students' perceived disease risk versus actual prevalence rates.
To compare college students' perceived disease risk with disease prevalence rates. Data were analyzed from 625 college students collected with an Internet-based survey. Paired t-tests were used to separately compare participants' perceived 10-year and lifetime disease risk for 4 diseases: heart disease, cancer, diabetes, and overweight/obesity. Respondents estimated their risk of developing heart disease as lower than cancer, yet rated their risk of developing heart disease as higher than diabetes and being overweight/obese. Incongruence between college students' perceived disease risk and disease prevalence rates calls for improved public health education.


The e-patient and medical students.
The recent publicity around the tragic case of Bronte Doyne has highlighted a pressing need in healthcare delivery: the need for doctors to know that their patients, "e-patients," know medicine. In turn, this requires our medical students to be trained in how best to utilise the potential of e-patients in healthcare delivery. "I can't begin to tell you how it feels to have to tell an oncologist they are wrong, it's a young person's cancer. I had to, I'm fed up of trusting them." - Bronte Doyne (Vize 2015).


CHOP vs MEV for the treatment of non-Hodgkin's lymphoma of unfavourable histopathology: a randomized clinical trial.
The Swedish Lymphoma Study Group has compared the results of treatment with a CHOP regimen (cyclophosphamide, adriamycin, vincristine and prednisone) with those of treatment with a MEV regimen (methotrexate, cyclophosphamide and vincristine) in patients suffering from generalized non-Hodgkin's lymphoma (NHL) of unfavourable histopathology in a prospective randomized trial. The complete remission rate for 67 evaluable patients receiving CHOP was higher (61%) than for 74 patients receiving MEV (24%) (P less than 0.001). The relapse rate was 18/41 (44%) in the CHOP group and 11/18 (61%) in the MEV group (difference not significant). At follow-up the number of patients alive in a first complete remission was thus 23/67 in the CHOP group but only 7/74 (9%) in the MEV group. This difference is highly significant (P less than 0.001). However, there is still no significant difference in overall survival between the two treatment groups. This is probably due to the more efficient rescue treatment (mainly CHOP) found in the patients who primarily received MEV than in those who primarily received CHOP. It is concluded that the CHOP regimen is superior to the MEV regimen in NHL patients with unfavourable histopathology.


Education differences in cardiometabolic risk in England, Scotland and the United States between 1992 and 2019.
Education differences in cardiometabolic risk and disease still play a major role in the magnitude of the socioeconomic health disparities in high-income societies. However, the knowledge on how education differences may have changed over time regarding the distribution of multiple risk factors is rather limited. This study aims to provide a comprehensive assessment of the magnitude of those differences in three high-income countries. Data from repeated cross-sectional population health and examination surveys conducted between 1992 and 2019 in England, Scotland and the United States are analysed (pooled sample size [Formula: see text]). Six cardiometabolic risk factors, namely, systolic and diastolic blood pressure, body-mass-index, glycated haemoglobin HbA1c, serum total cholesterol and the cardiovascular risk score are analysed with linear mixed models. Education differences in cardiometabolic risk were found to have either increased or remained stable for the past 3 decades in the countries included in the analyses. Among individuals with no qualification the cardiometabolic risk has been higher than among the higher educated (mean difference: 0.136, 99% CI [0.119; 0.152]). Education differences were observed also for systolic blood pressure (2.788 mmHg, 99% CI [2.529; 3.047]), glycated haemoglobin HbA1c (0.160 %, 99% CI [0.136; 0.185]), total cholesterol (0.268 mmol/L, 99% CI [0.247; 0.289]) and body-mass-index (0.591 kg/m2, 99% CI [0.504; 0.679]). The results suggest a more complex pattern of associations between education and health which may be due to education-dependent processes related to behavioural, cognitive and attitudinal modification and adaptation to changing socio-cultural conditions.


Online comment-based prediction of cosmetic ingredient's sensory irritation using gradient boosting algorithm.
The worldwide prevalence of "sensitive skin" group is estimated at being close to 40%. The main trigger for sensitive skin is the misuse of cosmetics products. Majority of the in vitro studies on cosmetic ingredients developed for topical application to the skin are not able to describe sensory irritation, such as stinging, burning, itching, and tingling. Besides, most of the in vivo tests often encounter problems such as limited number of subjects and usage scenarios deviate from reality. A gradient boosting algorithm is adopted in our context to integrate multisource of information including skin types, sensory response, and cosmetics ingredients to predict sensory irritation. In this study, online comments were preprocessed to construct a multi-dimensional structured data including skin types, sensory response, and cosmetics ingredients. A gradient boosting regression model was developed where sensory response was predicted based on the abovementioned structured input. The predictions were validated by in vivo test and were shown favorably when comparing with the state-of-the-art results from related works. 46 007 samples were collected after data cleaning and were used in model developing. Results showed that the model was capable to predict the sensory response of 16 skin types to different ingredients (R = 0.71, P < 10-10 ). In addition, this model was validated using data from in vivo studies and presented a value of 75% on specificity, 88.9% on sensitivity, and 82.4% on accuracy. Our approach that is based on a variant of the gradient boosting algorithm provided an adequate solution for understanding the sensory irritation of cosmetic ingredients.


Cold pressor test demonstrates residual sympathetic cardiovascular activation in familial dysautonomia.
In familial dysautonomia (FD), i.e. Riley-Day-syndrome, sympathetic cardiovascular function, as well as afferent temperature and pain mediating neurons, are significantly reduced. Thus, it was questioned if cold pressor test (CPT), which normally enhances sympathetic outflow and induces peripheral vasoconstriction by the activation of thermo- and nociceptive system activation, could be used to assess sympathetic function in FD. To evaluate whether CPT can be used to assess sympathetic activation in FD, we performed CPT in 15 FD patients and 18 controls. After a 35-min resting period, participants immersed their right hand and arm up to the elbow into 0-1 degrees C cold water while we monitored heart rate (HR), respiration, beat-to-beat radial artery blood pressure (BP), and laser Doppler skin blood flow (SBF) at the right index finger pulp. From these measurements, heart rate variability parameters were calculated: root mean square of successive differences (RMSSD), coefficient of variation (CV), low and high frequency (LF, HF) power spectra of the electrocardiogram (ECG). All participants perceived cold stimulation and indicated discomfort. In controls, SBF decreased and HR and BP increased rapidly upon CPT. After 60 s, SBF indicated secondary vasodilatation in six controls, BP rise attenuated and HR returned to baseline in all controls. In the patients, SBF remained unchanged, HR and BP increased significantly, but after 50-60 s of CPT and changes were lower than in controls (p<0.05). RMSSD and CV decreased and LF increased significantly only in the controls. We conclude that CPT activates sympathetic HR and BP modulation despite impaired pain and temperature perception in FD patients. BP increase in the presence of almost unchanged SBF might be due to HR increase and to nociceptive arousal and emotionally induced catecholamine release as seen in emotional crises of FD patients. CPT assesses sympathetic cardiovascular responses independently from baroreflex function, which is compromised in FD.


Outcome of Stable Patients With Acute Myocardial Infarction and Coronary Artery Bypass Surgery Within 48 Hours: A Single-Center, Retrospective Experience.
The optimal timing of coronary artery bypass grafting (CABG) in clinically stable patients with acute myocardial infarction who are unsuitable for percutaneous coronary intervention is unclear. We report our experience with early CABG in these patients. Between January 2001 and May 2015, 766 patients with ST-segment-elevation myocardial infarction (STEMI, n=305) or non-STEMI (NSTEMI, n=461) not including cardiogenic shock underwent CABG within 48 hours at our department. STEMI patients were younger than non-STEMI patients (age 65 years [range: 58-72] versus 70 years [range: 62-75], P<0.001) with a lower EuroSCORE II (4.12 [range: 2.75-5.81] versus 4.58 [range: 2.80-7.74], P=0.009). STEMI patients had undergone preoperative percutaneous coronary intervention more often (20.3% versus 7.8%, P<0.001). Time to surgery was shorter in STEMI compared with non-STEMI patients (5.0 hours [range: 3.2-8.8] versus 11.7 hours [range: 6.4-22.0], P<0.001). No significant differences concerning arterial graft use (93.8% versus 94.8%, P=0.540) or complete revascularization (87.5% versus 83.4%, P=0.121) were observed. The rate of strokes did not differ between the groups (2.0% versus 3.9%, P=0.134). Thirty-day mortality was lower in STEMI patients (2.7% versus 6.6% P=0.018), especially when CABG was performed within 6 hours (1.8% versus 7.1%, P=0.041). Survival of STEMI and non-STEMI patients was 94% versus 88% after 1 year (P<0.001), 87% versus 73% after 5 years (P<0.001), and 74% versus 57% after 10 years (P<0.001). Independent predictors of 30-day and long-term mortality included preoperatively increased lactate values, age, atrial fibrillation, and reduced left ventricular function. Stable STEMI patients showed a lower rate of perioperative complications and better survival compared with non-STEMI patients when CABG was performed within 48 hours.