Early CT findings of Fournier's gangrene in a healthy male.
Early clinical identification of Fournier's gangrene is imperative to avoid delay in the aggressive surgical debridement, antibiotic therapy, and sometimes hyperbaric oxygen treatments. We report on the early computed tomography findings of a non-gas-forming Fournier's gangrene in a healthy male to aid urologists, surgeons, and radiologists in the recognition of this rapidly progressive and often fatal infection.


Authentication of the medicinal plant Senna angustifolia by RAPD profiling.
In this study "RAPD" molecular marker was employed for the identification of Senna angustifolia, Senna acutifolia, Senna tora and Senna sophera. Total 32 decamer primers were screened in amplification with genomic DNA extracted from all species, of which 6 primers yielded species-specific reproducible bands. Out of 42 loci detected, the polymorphic, monomorphic and unique loci were 24, 2 and 16, respectively. Based on dendrogram and similarity matrix, 4 species were differentiated from each other and showed more divergence. Thus, this technique may prove and to contribute the identification of these species of Senna having similar morphology sold in the local markets.


The Cost of Uncertain Life Span.
A considerable amount of uncertainty surrounds the length of human life. The standard deviation in adult life span is about 15 years in the U.S., and theory and evidence suggest it is costly. I calibrate a utility-theoretic model of preferences over length of life and show that one fewer year in standard deviation is worth about half a mean life year. Differences in the standard deviation exacerbate cross-sectional differences in life expectancy between the U.S. and other industrialized countries, between rich and poor countries, and among poor countries. Accounting for the cost of life-span variance also appears to amplify recently discovered patterns of convergence in world average human well-being. This is partly for methodological reasons and partly because unconditional variance in human length of life, primarily the component due to infant mortality, has exhibited even more convergence than life expectancy.


Efficient charge transfer in cadmium sulfide quantum dot-decorated hierarchical zinc sulfide-coated tin disulfide cages for carbon dioxide photoreduction.
Constructing hybrid photocatalysts with advanced structures and controllable compositions is a promising way to improve CO2 photoreduction performance. In this work, SnS2 nanosheets are grown on ZnS polyhedron cages to fabricate hierarchical ZnS@SnS2 double-shelled heterostructured cages. This design integrates ZnS cages and SnS2 nanosheets into a stable heterostructured hybrid catalyst with a hierarchical double-shelled cage-like architecture, possessing abundant active sites, quick charge separation/migration, and high CO2 adsorption capacity. Benefiting from these advantages, the optimized hierarchical ZnS@SnS2 heterostructured cages exhibit significant gas-phase CO2 photoreduction activity with a CO generation rate of 95.38 μmol g-1h-1 and 72.4% CO selectivity, which are greatly improved in comparison with those of pure ZnS cages and nanosheet-assembled SnS2 particles. Furthermore, charge carrier separation efficiency and visible light harvesting ability are further improved by constructing a ZnS@SnS2/CdS type-I/type-II complex heterostructured system through surface decoration of CdS quantum dots. The optimized ZnS@SnS2/CdS hybrid exhibits a CO generation rate of 155.57 μmol g-1h-1 and an excellent selectivity of 80.4%. This work is conducive to the design and manufacture of advanced hybrids for solar energy utilization and photocatalytic reactions.


[Changes in the cartilage of the rat knee joint caused by running stress--a contribution to arthrosis research].
After running strain of Wistar-rats it is provable a small nonsignificant increase of the mean chondrocyte number per tissue area in the weight bearing cartilage of the medial femur condylus. Little foci of fibrillation and superficial localisated areas with loss of metachromasia are also visible in the cartilage. This tissue alterations appearing typical for a early phase of osteoarthrosis.


Peripheral blood mononuclear cell- transcriptome signatures of atopic dermatitis and prediction for the efficacy of dupilumab.
Few studies have explored transcriptome of the peripheral blood mononuclear cells (PBMCs) of atopic dermatitis (AD). Parameters for prediction of the efficacy of dupilumab in AD remain obscure. To explore transcriptome signature of the PBMCs from Chinese AD patients and the usage in predication for the efficacy of dupilumab. A total of 56 moderate-to-severe adult AD patients were enrolled and followed up for 16 week-dupilumab treatment. PBMCs samples were collected at baseline and 16 weeks after dupilumab treatment. Thirty-five patients were subjected to RNA-sequencing. Weighted gene co-expression network analysis (WGCNA) was used to find genes for prediction of dupilumab efficacy, which was validated in the rest 21 AD patients. Another 30 healthy individuals were enrolled and subjected to RNA-sequencing as healthy controls. Upregulation of the T helper (Th) 2/Th22 pathway, Th17 antimicrobial genes, and natural T-regulatory cell abundance in the PBMCs of AD cases was observed, whereas TGF-β signaling and NK-cell signaling were decreased. Dupilumab treatment reversed the increase in the expression of Th2 cytokine receptors. WGCNA identified two immune-related modules that were correlated significantly with the efficacy of dupilumab. Hub gene MAP2K3 and UBE2L3 of these two modules demonstrated potential predictive ability for efficacy in the RNA-sequencing group by Spearman correlation, ROC analysis, and regression analysis, which was further validated in additional 21 AD cases. We firstly revealed the molecular phenotype of PBMCs in Chinese patients with AD, and uncovered two molecules that might be useful for prediction of the efficacy of dupilumab.


Links between prolonged exposure to xenobiotics, increased incidence of hepatopathies, immunological disturbances and exacerbation of latent Epstein-Barr virus infections.
Disturbances of several humoral and cellular immune parameters are significantly increased in individuals exposed to chemical pollutants. Moreover, exacerbations of the latent Epstein-Barr virus (EBV) infection were more frequently observed in the chemically exposed group than in the control groups. A significant correlation was seen between EBV exacerbations and the increased number of eosinophils, T-lymphocyte rosette formation and the respiratory burst of polymorphonuclear blood cells. Possible links between hepatopathy due to xenobiotics exposition, immunological disturbances and EBV exacerbation are discussed, including a putative role of EBV-induced (autocrine) cytokines.


ATP modulation of mitogen activated protein kinases and intracellular Ca2+ in breast cancer (MCF-7) cells.
In the breast tumor cell line MCF-7, extracellular nucleotides induce transient elevations in intracellular calcium concentration ([Ca(2+)](i)). In this study we show that stimulation with ATP or UTP sensitizes MCF-7 cells to mechanical stress leading to an additional transient Ca(2+) influx. ATP> or =ATPgamma-S> or =UTP>>>ADP=ADPbeta-S elevate [Ca(2+)](i), proving the presence of P2Y(2)/P2Y(4) purinergic receptor subtypes. In addition, cell stimulation with ATP, ATPgamma-S or UTP but not ADPbeta-S induced the phosphorylation of ERK1/2, p38 and JNK1/2 mitogen activated protein kinases (MAPKs). The use of Gd(3+), La(3+) or a Ca(2+)-free medium, inhibited ATP-dependent stress activated Ca(2+) (SAC) influx, but had no effect on MAPK phosphorylation. ATP-induced activation of MAPKs was diminished by two PI-PLC inhibitors and an IP(3) receptor antagonist. These results evidence an ATP-sensitive SAC influx in MCF-7 cells and indicate that phosphorylation of MAPKs by ATP is dependent on PI-PLC/IP(3)/Ca(2+)(i) release but independent of SAC influx in these cells, differently to other cell types.


Dense Breast Notification Laws' Association With Outcomes in the US Population: A Cross-Sectional Study.
Understanding whether states' breast density notifications are associated with desired effects, or disparities, can inform federal policy. We examined self-reported receipt of personal breast density information, breast density discussions with providers, knowledge about density's masking effect, and association with increased breast cancer risk by state legislation status and women's sociodemographic characteristics. Cross-sectional observational population-based telephone survey of women aged >40 years who underwent mammography within prior 2 years, had no history of breast cancer, and had heard the term "breast density." Among 2,306 women, 57% received personal breast density information. Multivariate regression models adjusted for covariates indicated that women in notification states were 1.5 times more likely to receive density information, and older Black and Asian women of lower income and lower health literacy were less likely. Overall, only 39% of women discussed density with providers; women in notification states were 1.75 times as likely. Older and Asian women were less likely to have spoken with providers; women with high literacy or prior biopsy were more likely. State legislation status was not associated with differences in density knowledge, but Hispanic women and women of lower income or low health literacy had less knowledge regarding density's masking effects; older women were more knowledgeable. Hispanic women and women of lower income or low health literacy were more likely, and middle-aged women less likely, to recognize increased breast cancer risk. Some positive effects were observed, but sociodemographic disparities suggest tailoring of future breast density communications for specific populations of women to ensure equitable understanding.


Observation of coherent phonon-plasma coupled modes in wide gap semiconductors by transmission pump-probe measurements.
We have investigated coherent LO phonon properties in zinc-based II-VI widegap semiconductors, focusing on phonon-plasma coupled modes. By a careful treatment of the time evolution of the signals in ZnS, ZnSe, and ZnTe, we found a frequency upshift as the pump intensity increases. Using a classical coupled oscillator model, we have explained the pump intensity dependence of both the shift and the decay rates by a mixing of highly damped two-photon generated plasma. From the linear dependence between them we can estimate the photo-excited carrier mobilities, leading to a new powerful estimation method to measure the mobility.


Predictive value of plasma volume status for contrast-induced nephropathy in patients with heart failure undergoing PCI.
Contrast-induced nephropathy remains a common complication of coronary procedure and increases poor outcomes, especially in patients with heart failure. Plasma volume expansion relates to worsening prognosis of heart failure. We hypothesized that calculated plasma volume status (PVS) might provide predictive utility for contrast-induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention (PCI). We enrolled 441 patients with heart failure undergoing elective PCI from 2012 to 2018. Pre-procedural estimated PVS by the Duarte's formula (Duarte-ePVS) and Kaplan-Hakim formula (KH-ePVS) were calculated for all patients. CIN was defined as an absolute serum creatinine (SCr) increase ≥0.5 mg/dL or a relative increase ≥25% compared with the baseline value within 48 h of contrast medium exposure. We assessed the association between PVS and CIN in patients with heart failure undergoing elective PCI. In 441 patients, 28 (6.3%) patients developed CIN. The median Duarte-ePVS was 4.44 (3.87, 5.13) and the median KH-ePVS was -0.03 (-0.09, 0.05). The best cutoff values for Duarte-ePVS and KH-ePVS to predict CIN were 4.64 (with 78.6% sensitivity and 61.7% specificity) and 0.04 (with 64.5% sensitivity and 75.5% specificity), respectively. After adjusting for potential confounding variables, KH-ePVS > 0.04 [odds ratio (OR) 2.685, 95% confidence interval (CI) 1.012-7.123, P = 0.047] remained significantly associated with CIN whereas Duarte-ePVS was not. Pre-procedural KH-ePVS is an independent risk factor for CIN in patients with heart failure undergoing elective PCI. The best cutoff point of KH-ePVS for predicting CIN was 0.04.


Detection of equine arteritis virus (EAV) by polymerase chain reaction (PCR) and differentiation of EAV strains by restriction enzyme analysis of PCR products.
A polymerase chain reaction (PCR) based assay capable of detecting and differentiating seven strains of equine arteritis virus (EAV) from around the world was developed. The primers for the PCR were chosen from the ORF6 gene encoding the unglycosylated membrane protein (M). Viral RNA from cell culture fluids infected with each of the seven EAV strains and RNA from the live vaccine, Arvac, was detected by PCR using four sets of primers. The sensitivity of detection was increased from 100 to 1,000 times by performing nested PCR enabling the detection of RNA at a level of 0.5-5 PFU. Differentiation among the virus strains and the live vaccine was achieved by cutting the PCR-amplified products from three sets of primers with six restriction endonucleases. Using this procedure it was possible to distinguish among the seven EAV strains used.


Specific Antibody Deficiencies.
Patients with specific antibody deficiency (SAD) have a deficient immunologic response to polysaccharide antigens. Such patients experience sinopulmonary infections with increased frequency, duration, or severity compared with the general population. SAD is definitively diagnosed by immunologic challenge with a pure polysaccharide vaccine in patients 2 years old and older who have otherwise intact immunity, using the 23-valent pneumococcal polysaccharide vaccine as the current gold standard. Specific antibody deficiencies comprise multiple immunologic phenotypes. Treatment must be tailored based on the severity of symptoms. Most patients have a good prognosis. The deficiency may resolve over time, especially in children.


5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary arterial hypertension: A meta-analysis.
The influence of 5-HTT, BMPR2, EDN1, ENG, KCNA5 genes polymorphisms on susceptibility of pulmonary arterial hypertension remains uncertain. This meta-analysis is conducted for further study. We conducted a literature search on PubMed and ISI web of science databases for searching relevant articles until November 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 17 articles with 2631 PAH subjects and 5139 controls were included in the final meta-analysis. Statistical software Stata13.0 was used for data-analysis. A significant relationship was found between the 5-HTT L/S polymorphism and PAH in all the genetic models [LL vs. SS: OR = 1.60, 95% CI, 1.11-2.32; LS vs. SS: OR = 1.55, 95% CI, 1.10-2.21; (LS + LL) vs. SS: OR = 1.56, 95% CI, 1.13-2.17; L vs. S: OR = 1.32, 95% CI, 1.08-1.62]. There were also associations of the SERT L/S polymorphism with IPAH and PAH in COPD [IPAH L/S: OR = 1.26, 95% CI, 1.01-1.57; PAH in COPD L/S: OR = 1.42, 95% CI, 1.04-1.94]. In addition, the results showed a statistically significant association between EDN1 rs5370 polymorphism and the risk of PAH in all the genetic models [TT vs. GG: OR = 3.32, 95% CI, 1.30-8.51; TG vs. GG: OR = 2.68, 95% CI, 1.54-4.66; (TG + TT) vs. GG: OR = 2.82, 95% CI, 1.69-4.71; T vs. G: OR = 2.43, 95% CI, 1.60-3.68]. However, the significant association was not found between BMPR2 rs1061157, KCNA5 rs10744676, ENG rs3739817 polymorphisms and the risk of PAH (all p > 0.05). 5-HTT L/S polymorphism and END1 rs5370 polymorphism were correlated with significantly increased risk of PAH. Moreover, L allele in 5-HTT gene increased susceptibility to IPAH and PAH in COPD.


Distance and the utilization of health facilities in rural Nigeria.
The distance patients must travel in order to obtain treatment has long been recognized as a primary determinant of the utilization of health care facilities. The distance factor is especially significant in rural Third World settings where the density of Western-type health facilities is often low, where the majority of patients are likely to make the journey for treatment as pedestrians and where there are viable and usually more accessible alternate sources of medicine. This study examines the impact of distance on the utilization of health care facilities in the Hadejia area of Kano State, Nigeria. Per capita utilization was found to decline exponentially with distance. The rate of distance decay in utilization levels varies according to the type of facility, socio-demographic variables and illness. Hausa perceptions about sickness and about specific illnesses are reflected in the varying incidence of health facility utilization in the treatment of particular illnesses and distance decay gradients of varying steepness. Although the per capita consumption of health care decreases exponentially for concentric distance bands, individual villages show great disparities in utilization rates which are only partly attributable to distance.


Updated guidance on medical emergencies and resuscitation in the dental practice.
This article outlines the updated guidance relating to the management of medical emergencies in the dental practice. The incidence of medical emergencies in the dental practice is discussed. The key recommendations from the Resuscitation Council UK on the treatment of medical emergencies in the dental practice are listed, with specific reference to oxygen therapy, medications and automated external defibrillators. An overview to the professional responsibilities of dental practitioners and dental care professionals is provided.


Immunological relationship among human adenoviruses of subgenus D.
Antigenic relationships between adenoviruses of subgenus D were determined by neutralization tests in HeLa cell cultures by CPE inhibition. For cross-testing, several antisera of the same species were tested against the prototype viruses. 39 wild strains belonging to 12 different virus species were also studied. Marked variation in the degree of cross-neutralization between individual sera of the same species was often observed. However, virus strains within a species mostly showed identical serological reactions. Hence, antigenic specificity appears to be a fairly constant property of any one species. Strong cross-neutralizations between species are presumably due to a relationship of the hexon (hexon) antigen, whereas weak cross-neutralizations found between viruses related by hemagglutination-inhibition are due to the gamma (fiber) antigen. Viruses related to adenovirus 15 (Mastadenovirus h 15) showed a variety of cross-reactions in neutralization tests. In view of the new species definitions of adenoviruses and to facilitate identification, changes in the classification of Ad 15, 25, 29, and 15/H9 are proposed. The prototypes of Ad 13, 15, 25, 29, and 30 have been cloned by terminal dilution.


Interface morphology and gas production by a refractive 347 nm ultraviolet femtosecond laser: Comparison with established laser systems.
To evaluate gas production and interface quality after refractive lenticule creation. A new ultraviolet (UV) 347 nm femtosecond laser was compared with the FS200 and the Visumax lasers. Department of Anatomy II, University of Erlangen-Nürnberg, Erlangen, Germany. Experimental study. Refractive lenticules were created in 52 porcine corneas with the UV laser (n = 20), the Visumax laser (n = 20), and a modified FS200 laser (n = 12). Twelve corneas in each laser group were fixed immediately after lenticule creation to entrap the gas produced. Lenticule extraction was omitted. From 16 other corneas (UV and Visumax lasers; n = 8 each) -5.0 diopter (D) and -10.0 D lenticules were extracted. On lenticule extraction, a flap was created and lifted. In 12 additional corneas, a flap was cut using the FS200 laser and lifted afterward; laser in situ keratomileusis was performed on 8 of these samples. The corneas were processed for light microscopy (gas bubble 2-dimensional morphometry) and scanning electron microscopy (interface quality). The Visumax generated approximately one half as much gas as the FS200. The UV laser undercut the Visumax by another 50%. The interfaces created by the FS200 appeared smooth and without irregularities. The optical zone margin was always conspicuous in the Visumax samples but hardly discernible in the UV specimens. Slight irregularities and very small lenticule pieces were found occasionally in both groups. The UV interfaces appeared slightly rougher than the Visumax interfaces. Ultraviolet laser lenticule extraction seems promising. The interface quality was similar to that of the clinical Visumax system while gas production was reduced significantly.


Capsule phase microextraction of six bisphenols from human breast milk using a monolithic polyethylene glycol sorbent-based platform prior to high performance liquid chromatography-photo-diode array detection determination.
The determination of bisphenols in human breast milk is a matter of ongoing interest since it reveals the exposure levels in both lactating mothers, fetuses, and infants. Herein, capsule phase microextraction (CPME) is applied for the first time for the extraction of a mixture of bisphenols from human breast milk followed by their subsequent determination by high-performance liquid chromatography-photodiode array detection (HPLC-DAD). CPME is a recently introduced as an advanced micro preparative technique that meets the principles of Green Analytical Chemistry. Moreover, it integrates filtration, extraction and stirring mechanism into one single device, a composite attribute that allows selective extraction of analytes without any sample cleanup and facilitates faster extraction kinetics, resulting in enhancing the performance of the equilibrium-based extraction techniques that ensure better reproducibility and operational simplicity. Among four tested CPME devices, the sol-gel poly(ethylene glycol) capsules showed the best extraction efficiency. Critical factors of the extraction performance were investigated and optimized. The developed CPME-HPLC-PDA method was validated. Limits of detection and quantification were 7.58 ng/mL and 25 ng/mL, respectively. Relative recoveries were estimated between 89.7 and 110.5%, while the RSD values were <11% in all cases. CPME is poised to be a useful tool both for routine bioanalysis and research purposes.


Natural host defence during oncogenesis. NK activity and dimethylbenzanthracene carcinogenesis.
In this study we determined the effect of administering the chemical carcinogen dimethylbenzanthracene (DMBA) on NK activity mediated by murine splenocytes. The intragastric administration of six weekly 1-mg doses of DMBA to 2- to 3-month-old mice either following a pituitary graft or not, resulted in a tumor incidence which was higher than 60%. The cellularity of the spleens decreased significantly after the third DMBA feeding and the NK activity of these spleens was selectively suppressed. There was no spontaneous reconstitution of the NK activity following cessation of DMBA treatment and during the entire tumor-free period. The adoptive transfer of normal bone marrow, thymus or spleen cells did not restore NK activity in DMBA-treated mice. The NK activity of DMBA-fed mice could be augmented by interferon and by interferon inducers such as poly I:C and dsRNA from Ustilago virus. The effect of these biological response modifiers on NK activity was short-lived but it was possible to restimulate this activity every 24 h. Consecutive treatments of DMBA-fed mice with poly I:C maintained a high level of NK activity for at least 3 weeks.


Effectiveness of multimedia education for reducing anxiety among caregivers of children and adolescents undergoing chemotherapy: Randomized controlled trial protocol.
Childhood cancer affects approximately 600,000 children and adolescents worldwide, and chemotherapy is the main form of treatment. However, chemotherapy treatment causes feelings of fear and anxiety especially in the patient's caregiver. Thus, strategies that help the health education process directed towards caregivers are essential for strengthening knowledge and reducing anxiety involved with the beginning of treatment. To present a study protocol to evaluate the effect of a multimedia strategy compared to standard guidelines for acquiring knowledge and reducing anxiety among caregivers of children and adolescents with cancer undergoing chemotherapy. A randomized, controlled, single-blind, two-armed clinical trial will be carried out. Fifty-two caregivers of children and adolescents who will start chemotherapy will participate in the study, which will be randomly assigned into Experimental Group, which involves the evaluation of the effect of a multimedia strategy composed of a digital animation film about the chemotherapy process, used as tool for health education or into Control Group, which assesses the effects of standard guidelines, which are verbally provided. Two important moments will be considered to evaluate the results of the intervention (P1, and F1). The primary outcome includes reduced anxiety and the secondary outcome refers to the caregivers' acquisition of knowledge about chemotherapy treatment. The results of this randomized clinical trial will have a positive impact on the participants' knowledge acquisition, and will also contribute to reduce anxiety observed at the beginning of treatment related to the caregivers' knowledge deficit. The level of knowledge between groups with anxiety before and after intervention will be compared, highlighting which intervention had the best effect. Registration: RBR-4wdm8q9-Brazilian Registry of Clinical Trials-REBEC (23/03/2022). This study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte- UFRN, under CAAE-52597121.9.0000.5537.


Terbium identifies double-stranded RNA on gels by quenching the fluorescence of intercalated ethidium bromide.
We report that the lanthanide cation terbium quenches the fluorescence of ethidium bromide bound to double-stranded RNA by 40-fold, whereas the quenching of double-stranded and single-stranded DNA is under 2.5-fold and the quenching of single-stranded RNA is under 5-fold. This observation was used to develop a convenient method of detecting dsRNA among other nucleic acids in an agarose or polyacrylamide gel. The sensitivity of the method is approximately 4 ng/mm2.


Disclosing the composition of unknown historical drug formulations: an emblematic case from the Spezieria of St. Maria della Scala in Rome.
This paper reports a pioneering study of an unknown historical drug formulation preserved in the Spezieria of Santa Maria della Scala in Rome, founded at the end of the seventeenth century by the Discalced Carmelites. Due to limited literature related to pharmaceutical remedies and drugs of the Early Modern Era (between the XV and XVIII centuries) and the complexity in their formulations, the study of these drugs represents a great challenge. The untargeted nature of the selected drug required a multi-analytical approach with complementary techniques to formulate a compositional hypothesis: FT-IR spectroscopy, gas chromatography-associated/mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) were successfully employed to identify different organic compounds. Systematic archaeobotanical research was performed as well, allowing us to acquire data related to the possible genus of plants from which these natural compounds derive and their geographical origin. The unknown drug formulation turned out to be a complex mixture used as an ointment with an anti-inflammatory purpose. It mainly contains a mixture of Venetian turpentine; a Pine resin (colophony) from the Pinaceae family; an exudate of a plant from South America, whose identified components are triterpenic compounds such as alpha- and beta-amyrins, betulin and lupeol; and saturated fatty acids which act as carriers and/or to reduce the viscosity of abovementioned exudates and resins. The study of historical drugs is important not only in order to know the practices handed down by the speziali in the past but also to reconstruct historical recipes, which can inspire new dermatological, cosmetic, hygienic and current healing products.Graphical abstract.


Combined modality therapy for esophageal cancer.
Treatment approaches for esophageal cancer include primary treatment (surgical or nonsurgical) or adjuvant treatment (preoperative or postoperative). Primary treatments include surgery alone, radiation therapy alone, and radiation therapy plus chemotherapy (combined modality therapy). Adjuvant therapies include preoperative or postoperative radiation therapy, preoperative chemotherapy, and preoperative combined modality therapy. There is considerable controversy as to the ideal therapeutic approach. This review will examine the results of these approaches as well as combined modality therapy using novel regimens.


A new layered photocathode with porous NiO nanosheets: an effective candidate for p-type dye-sensitized solar cells.
Herein, with the purpose of improving the efficiency of p-type dye-sensitized solar cells (DSSCs), a new layered photocathode (LP) is fabricated from irregular overlapping wrinkled porous NiO nanosheets. The LP was sensitized by using a commonly used dye, coumarin 343(C343), and then assembled into p-type DSSCs through coupling with a platinum photoanode. Photoelectochemical characterization showed that the LP cell exhibited a clearly enhanced power-conversion efficiency (by a factor of 4) compared with a cell with a NiO-nanoparticle photocathode (NP). This excellent performance could be attributed to the overlapping layered structure, which favored hole transport, as confirmed by electrochemical impedance spectroscopy, and to the large surface area of the porous NiO nanosheets, which were favorable for dye adsorption.


Characterization of a new decahydropyridoquinoline from Indigofera longeracemosa Boiv. ex Baill. (Fabaceae).
Repeated silica gel chromatography of the dichloromethane extract of air-dried stems of Indigofera longeracemosa followed by reverse-phase HPLC separation yielded a new decahydropyridoquinoline, rel-(3S, 5R, 6S, SR, 8aR, 12aR)-8-acetoxy-6-butyl-3-isothiocyanatodecahydropyrido (2,1) quinoline.


Do women have an accurate perception of their pelvic floor muscle contraction? A cross-sectional study.
To assess women's self-perception of their pelvic floor muscle (PFM) contraction and its agreement with an assessed PFM contraction. Further, to assess a possible correlation between women's self-perception and reports of urinary incontinence (UI) and between PFM contraction and severity of UI. A cross-sectional observational study including 82 women. The study was conducted in a basic healthcare unit in Brazil. PFM contraction was assessed by a physiotherapist and estimated by women using the Modified Oxford Scale (MOS). UI symptoms were assessed using a validated questionnaire (ICIQ-UI-SF). A descriptive analysis of the data was performed. The weighted κ coefficient, Spearman's correlation coefficient, and Fisher's exact test were used to analyze data. Eighty-two women with a mean age of 46.83 (±17.94) were analyzed. The majority (98.8%) believed they were able to voluntarily contract their PFM, but only 33% correctly estimated their PFM considering the examiner assessment as reference. No agreement (κ = 0.139, P = .087) was found between the examiner's classification and the women's estimation of their PFM contraction. Women's self-perception did not correlate with the ICIQ-IU-SF (r's = .011, P = .922). A moderate negative correlation was found between the assessed PFM contraction and the ICIQ-UI-SF score (r's = -.406, P = .00). Most of the women did not show an accurate self-perception of PFM contraction. No correlation between women's self-perception and the ICIQ-UI-SF score was found, but a negative correlation was found between the assessed PFM contraction and the ICIQ-UI-SF score.


Sonoembryology of the fetal posterior fossa at 11 + 3 to 13 + 6 gestational weeks on three-dimensional transvaginal ultrasound.
To describe the sonographic appearance and temporal changes of the structures of the posterior cranial fossa in fetuses at a crown-rump length (CRL) between 45 and 84 mm in transvaginal acquired three-dimensional volume blocks. This was a prospective, cross-sectional, observational study including 80 fetuses, whose mothers attended Kepler University Hospital Linz or the Ambulatorium für Fetalmedizin Feldkirch for first-trimester sonography. Three-dimensional volume blocks were acquired in a standardized way and after processing the sonographic characteristics of the brainstem, cerebellar vermis, choroid plexus, anterior membranous area (AMA) and Blake's metapore were described. Measurements of the length of the cerebellar vermis, the length of the AMA and the medulla-oblongata-pons angle (MOPA) were performed. In 20 fetuses the intra- and interobserver repeatability was calculated. The sonomorphologic characteristics of posterior fossa structures as cerebellar vermis, AMA, Blake's metapore, choroid plexus, pons and medulla oblongata were described. There is a significant correlation between CRL and vermis length, CRL and MOPA and CRL and AMA. Transvaginal three-dimensional sonography allows a detailed depiction of the structures of the posterior fossa and their temporal course in early pregnancy. © 2016 John Wiley & Sons, Ltd.


Oviposition choices by a pre-dispersal seed predator (Hylemya sp.) : I. Correspondence with hummingbird pollinators, and the role of plant size, density and floral morphology.
Although the importance of pollinators has most often been examined in the evolution of floral characters, seed predators may also play a role in shaping floral evolution. In this study, I examined the role of interplant distance, plant size, and flower morphology on Ipomopsis aggregatás (Polemoniaceae) attractiveness to a pre-dispersal seed predator, Hylemya sp. (Anthomyiidae) and to hummingbird pollinators. The attractiveness of I. aggregata individuals to Hylemya was nonlinearly related to interplant distance in experimental arrays. Clumped and highly dispersed plants were preyed upon more frequently than those at intermediate distances. I found no relationship between interplant distance and visitation rates by hummingbird pollinators in these experimental arrays. However, in natural populations studied, clumped plants were more frequently approached by hummingbirds than those growing more widely dispersed. Display size was unrelated to visitation by Hylemya on inflorescences I clipped and maintained as "large", "small" and "control". Display size was also unrelated to the total number of visits by hummingbird pollinators to each of these experimental plants, however "large" display plants were more likely to be visited first in any given visitation sequence. Of various morphological measurements, corolla length showed the strongest positive correlation with Hylemya egg presence. To the extent that plant spacing and morphology is correlated with pollinator visits and ultimate seed set, Hylemya could be choosing flowers optimally, and playing a role in the evolution of floral traits.


Breakthrough disseminated Aspergillus ustus infection in allogeneic hematopoietic stem cell transplant recipients receiving voriconazole or caspofungin prophylaxis.
Aspergillus ustus is an uncommon clinical species which is poorly susceptible to antifungals. We report two cases of A. ustus infections that occurred in allogeneic stem cell transplant recipients while they were receiving either voriconazole or caspofungin. Prolonged use of these new antifungal agents may increase the risk of the emergence of resistant organisms.


Development and validation of a sensitive flow cytometric method for determining CECs in RBC products.
Subpopulations of immature red blood cells (RBCs) named CD71+ erythroid cells (CECs) with different properties may contribute to RBC transfusion outcomes. However, it is challenging to quantify CECs in leukoreduced RCCs and whole blood due to their rarity and fragility. Current flow cytometry methods are not applicable to leukoreduced RCCs as there is limited peripheral blood mononuclear cells (PBMCs) to use for determination of CECs. We have developed and validated a flow cytometry method for quantifying CECs in WB. We determined optimal PE-Cy7-CD235a, BV711-CD71, APC-CD45 concentrations and instrument setting by titration. Linearity and level of detection was determined by spiking labelled PBMCs from cord blood units into unlabeled WB. Low, medium, high levels of CECs were used to determine intra- and inter -run precision. Detection of CECs was linear (R2 = 0.98) over the range of concentrations assessed with a limit of detection of 0.005%. The overall CVs for the intra- and inter-run precision were 6.9% and 9.7%. We developed a simple, sensitive, and cost-effective flow cytometric method for quantifying the proportion of CECs in non-manipulated WB, which could help understand the impact of RBC products on recipient transfusion outcomes.


Inter-Sensor Calibration between HY-2B and AMSR2 Passive Microwave Data in Land Surface and First Result for Snow Water Equivalent Retrieval.
The self-designed HaiYang-2B (HY-2B) satellite was launched on 24 October 2018 in China at 22:57 UT in a 99.34° inclination sun-synchronous orbit. The Scanning Microwave Radiometer (SMR) on the core observatory has the capability to provide near-real-time multi-channel brightness temperature (Tb) observations, which are designed mainly for improving the level of marine forecasting and monitoring, serving the development and utilization of marine resources. After internal calibration and ocean calibration, the first effort to retrieve land surface snow parameters was performed in this study, which obtained extremely low accuracy both in snow extent and snow mass. Accordingly, land inter-sensor calibration was carried out between SMR and the Advanced Microwave Scanning Radiometer 2 (AMSR2) in order to broaden the research and application of SMR data on the Earth's land surface. Finally, we evaluated the consistency of the snow extent and snow mass derived from the initial and land-calibrated SMR data. The results indicated that a systematic SMR cold deviation whose magnitude depends on the channel is present for all the compared channels. After intercalibration, the conformity of the snow extent and snow mass were substantially improved compared to before; the relative bias of the snow extent and snow mass decreased from -49.97% to 2.97% and from -51.71% to 3.01%, respectively.


Quantification of Bioactive Metabolites Derived from Cell-Free Supernatant of Pediococcus acidilactici and Screening their Protective Properties in Frankfurters.
The specific aims of the current study were to determine and quantify the bioactive compounds derived from the cell-free supernatant (CFS) of Pediococcus acidilactici and screen their protective effect in frankfurters by applying an edible coating. This was achieved by immersing the peeled frankfurters in the CFS (CFS: 50% and 100%) alone or in combination with chitosan (CH: 0.5% and 1%) solutions for 3 min. Untreated frankfurter samples (control) exceeded the maximum acceptable total viable count limit (7.0 log10) on the 14th day, whereas samples treated with 100% CFS + 1% chitosan reached the limit on day 28 during refrigerated storage (P < 0.05). This treatment provided a 14-day extension to the shelf life of frankfurters without causing any significant changes in color and sensory attributes (P > 0.05). Additionally, this treatment inhibited oxidation in the frankfurters, leading to no significant changes in TBA and TVB-N within this group during storage (P > 0.05). This protective effect was mainly attributed to the wide variety of bioactive compounds identified in the CFS, including a total of 5 organic acids, 20 free amino acids, 11 free fatty acids, 77 volatiles, and 10 polyphenols. Due to these bioactive compounds, CFS exhibited a strong radical scavenging capacity (DPPH: 435.08 TEAC/L, ABTS: 75.01 ± 0.14 mg TEAC/L; FRAP: 1.30 ± 0.03 mM FE/L) and antimicrobial activity against microorganisms primarily responsible for the spoilage of frankfurters. In conclusion, the results indicate that the CFS contains high levels of bioactive metabolites, and an edible chitosan coating impregnated with CFS can be utilized to extend the shelf life of frankfurters through its antimicrobial effects and oxidation stabilization.


Small-molecule light-emitting electrochemical cells: evidence for in situ electrochemical doping and functional operation.
We demonstrate that non-ionic small molecules (SMs) can function as the doping and emissive compound in light-emitting electrochemical cells (LECs), and that high brightness and decent efficiency can be attained for such devices. It is plausible that the expansion of the LEC library, to include easy-to-purify and tunable non-ionic SM compounds, could represent a viable path towards improved LEC devices.


Effects of molecular crowding by saccharides on alpha-chymotrypsin dimerization.
Given the importance of protein complexes as therapeutic targets, it is necessary to understand the physical chemistry of these interactions under the crowded conditions that exist in cells. We have used sedimentation equilibrium to quantify the enhancement of the reversible homodimerization of alpha-chymotrypsin by high concentrations of the osmolytes glucose, sucrose, and raffinose. In an attempt to rationalize the osmolyte-mediated stabilization of the alpha-chymotrypsin homodimer, we have used models based on binding interactions (transfer-free energy analysis) and steric interactions (excluded volume theory) to predict the stabilization. Although transfer-free energy analysis predicts reasonably well the relatively small stabilization observed for complex formation between cytochrome c and cytochrome c peroxidase, as well as that between bobtail quail lysozyme and a monoclonal Fab fragment, it underestimates the sugar-mediated stabilization of the alpha-chymotrypsin dimer. Although predictions based on excluded volume theory overestimate the stabilization, it would seem that a major determinant in the observed stabilization of the alpha-chymotrypsin homodimer is the thermodynamic nonideality arising from molecular crowding by the three small sugars.


Patients who have dilated cardiomyopathy must have a trial of bridge to recovery: the case against that proposition.
The idea that patients who have dilated cardiomyopathy (presumably a large heart with near-normal coronary arteries) must have a trial of bridge to recovery is risible. Many such patients should be managed so that they go directly to transplantation and others may be better treated with drug therapy. Some may be more suited to destination therapy. What is needed in this field is more precise terminology, clearer statements of clinical intent at the time of device insertion, improved characterization of patients, more accurate clinical assessment, and above all more information from randomized clinical trials.


Larval development of Neostrongylus linearis (Nematoda, Protostrongylidae) in the mollusc Cochlicella barbara infected and maintained in a subhumid area (north-west Spain) and its possible influence on the infection of small ruminants.
Twelve batches of 100 Cochlicella barbara (Mollusca, Helicidae) were deposited monthly, from January to December in plots (0.5 x 0.5 m) with faeces of sheep containing first-stage larvae of Neostrongylus linearis in order to be naturally infected, and another 12 batches acted as uninfected controls. Every 2 weeks dead molluscs were removed from the plots and three to five specimens were examined to study larval development in the snail. Infected and control snails did not differ in their mortality, which may be associated with the low rate of infection of snails. The highest number of molluscs that were infected and the maximum level of infection were observed in batches deposited in summer months. There was a positive correlation between the percentage of infected snails and temperature. Molluscs harboured higher number of infectious third-stage larvae (L3) from mid-spring to mid-autumn and especially in summer months; thus under these climatic conditions and periods small ruminants are more likely to get infected by N. linearis.


Cerebrospinal fluid: the role of biochemical analysis.
Biochemical analysis of cerebrospinal fluid may provide answers to important clinical questions. This review summarizes these questions and outlines the value and limitations of cerebrospinal fluid analysis.


Efficacy and Safety of First-Line Cytokines versus Sunitinib and Second-Line Axitinib for Patients with Metastatic Renal Cell Carcinoma (ESCAPE Study): A Phase III, Randomized, Sequential Open-Label Study.
The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7-46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3-26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121-1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418-6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522.


Priority assessment of patients for elective general surgery: game on?
Clinical priority assessment criteria (CPAC) are used to generate a score by which patients are prioritized and rationed for elective surgery. It is widely believed that surgeons elevate scores to ensure their patients' acceptance for elective surgery, colloquially called gaming. The purpose of the present paper was therefore to investigate whether there was a temporal trend to an increase in the assigned priority score from the inception of CPAC to the present. Priority and weighted inlier equivalent separations (WIES) scores between 23 April 1999 and 23 July 2002 were collected for elective general surgical cases at Auckland Hospital. A total of 5440 cases was retrospectively analysed using multiple regression techniques. Priority score was included as the dependent variable and time as an independent variable. Any change in case complexity over that period was accounted for by including the WIES score as a covariate. Multiple regression was undertaken for the combined surgeons and for individuals. The combined model was statistically significant but accounted for only 17% of the priority score variance. An increase of one WIES unit leads to an increase of 2.7 in priority score (P=0.0001). The relationship of priority score with time was dependent on the surgeon performing the prioritization. However, only half the surgeons had individual models that indicated gaming. The results show that gaming is occurring but that not all surgeons participate in this. The difference between surgeons' participation in gaming is a potential source of practice variation in the prioritization process.


Influence of reinforcer type and route of administration on gamma-hydroxybutyrate discrimination in rats.
Possible effects of reinforcer type on the results of drug discrimination studies have not been examined systematically, but different deprivation operations and differentially effective reinforcers might well influence outcomes. Therefore, this study examined the influence of reinforcer (food or water) as well as route of administration (IP or IG) on gamma-hydroxybutyrate (GHB) discrimination. Four separate groups of six rats were trained under a resetting fixed-ratio schedule to discriminate between 300 mg/kg GHB and vehicle under these conditions, then generalization tests were conducted with gamma-butyrolactone (GBL), 1,4-butanediol (1,4-BD), ethanol, and ethanol plus 150 mg/kg GHB. Food maintained significantly higher response rates than water, but there were no significant differences among the four training groups in response accuracy or sessions required to meet the discrimination criterion. Training conditions significantly affected the results of stimulus generalization tests. The IG-Water group was most sensitive to a lower dose of GHB, and only the IP-Water group failed to generalize to orally-administered GHB. Gamma-butyrolactone and 1,4-butanediol fully substituted in all except the IP-Food group. Ethanol did not fully substitute for GHB in any group, and the combination of GHB (150 mg/kg) and ethanol did not have additive effects. These results demonstrate that methodological variables during drug discrimination training can certainly influence the results of stimulus generalization. Future investigations into the behavioral and/or physiological mechanisms that account for these effects are warranted.


Retraction Notice: Diabetes-Related Knowledge and Preventative Practices Among Government Employees with Diabetes in Kuwait.
[This retracts the article on p. e444 in vol. 17, PMID: 29372087.].


Structure of Salmonella effector protein SopB N-terminal domain in complex with host Rho GTPase Cdc42.
SopB is a type III secreted Salmonella effector protein with phosphoinositide phosphatase activity and a distinct GTPase binding domain. The latter interacts with host Cdc42, an essential Rho GTPase that regulates critical events in eukaryotic cytoskeleton organization and membrane trafficking. Structural and biochemical analysis of the SopB GTPase binding domain in complex with Cdc42 shows for the first time that SopB structurally and functionally mimics a host guanine nucleotide dissociation inhibitor (GDI) by contacting key residues in the regulatory switch regions of Cdc42 and slowing Cdc42 nucleotide exchange.


Mediating toxic emotions in the workplace--the impact of abusive supervision.
This study explores whether abusive supervision can effectively predict employees' counterproductive work behaviour (CWB) and organisational citizenship behaviour (OCB) and the role of toxic emotions at work as a potential mediator of these relationships in nursing settings. Workplace bullying is widespread in nursing. Despite the growing literature on abusive supervision and employees' counterproductive work behaviour and organisational citizenship behaviour, few studies have examined the relationships between abusive supervision and these work behaviours from the viewpoint of the victimed employee's emotion process. This study adopted a two-stage survey of 212 nurses, all of whom were employed by hospitals in Taiwan. Hypotheses were tested through the use of hierarchical multiple regression. The results showed that abusive supervision was positively associated with toxic emotions. Moreover, toxic emotions could effectively predict nurses' counterproductive work behaviour and organisational citizenship behaviour. Finally, it was found that toxic emotions partially mediated the negative effects of abusive supervision on both work behaviours. Toxic emotions at work are a critical mediating variable between abusive supervision and both counterproductive work behaviour and organisational citizenship behaviour. Hospital administrators can implement policies designed to manage events effectively that can spark toxic emotions in their employees. Work empowerment may be an effective way to reduce counterproductive work behaviour and to enhance organisational citizenship behaviour among nurses when supervisors do not promote a healthy work environment for them.


Mutagenesis of lysine 460 in the human insulin receptor. Effects upon receptor recycling and cooperative interactions among binding sites.
Mutations in the insulin receptor gene can cause insulin resistance. Previously, we have identified a mutation substituting glutamic acid for lysine at position 460 in the alpha-subunit of the insulin receptor in a patient with a genetic form of insulin resistance. In the present work, we have investigated the effect upon receptor function of amino acid substitutions at position 460. Decreasing the pH from 8.0 to 5.5 caused a progressive acceleration of the dissociation of 125I-insulin from the wild-type insulin receptor. Substitution of acidic amino acids (Glu or Asp) for Lys460 decreased the ability of acid pH to accelerate dissociation of 125I-insulin. In contrast, substitution of Arg or neutral amino acids (Val, Met, Thr, or Gln) had no effect upon the sensitivity to acid pH. Correlated with decreased sensitivity to acid pH, substitution of Glu or Asp at position 460 retarded the dissociation of 125I-insulin from intracellular receptors subsequent to receptor-mediated endocytosis. Furthermore, retardation of dissociation of 125I-insulin from the internalized receptor was associated with a decreased half-life of the receptor. In summary, the Glu460 mutation appears to cause insulin resistance by accelerating receptor degradation and, thereby, decreasing the number of insulin receptors on the cell surface. Additional studies suggested that Lys460 may provide the amino groups whereby disuccinimidyl suberate cross-links the two alpha-subunits to each other. Consistent with the hypothesis that Lys460 is located at the interface between adjacent alpha-subunits, substitutions at position 460 impair cooperative interactions among insulin binding sites. The Glu460 mutation decreases positively cooperative binding interactions; the Arg460 mutation impairs negative cooperativity. Mutations at position 460 in the alpha-subunit did not decrease the ability of insulin to stimulate receptor tyrosine kinase.


Determination of polychlorinated biphenyls in small-size serum samples by solid-phase extraction followed by gas chromatography with micro-electron-capture detection.
An new method for the determination of polychlorinated biphenyls (PCBs) in serum samples of up to 1 ml has been developed. The procedure consisted in the solid-phase extraction (SPE) of the analytes on an Oasis cartridge and the subsequent on-line elimination of the fat by directly dropping of the eluate from the SPE cartridge on a multilayer column placed below the cartridge. This configuration allowed minimising of the sample manipulation as well as the time, solvent and sorbent consumption (i.e. complete sample preparation can be accomplished in about 1 h with only 3 ml of toluene and 300 mg of silica). The SPE plus clean-up method developed showed a satisfactory performance for the analysis of PCBs in rat serum samples providing similar recoveries (i.e. range 73-128% for most of the congeners selected) at the different spiking levels investigated (1.25, 0.50 and 0.25 ng/ml). Detection limits using a microelectron capture detector were in the range 0.01-0.30 ng/ml of serum and the relative standard deviations of the complete method better than 18% irrespective of the PCB concentration. The validated method has been applied to the evaluation for the first time of the PCB levels in serum samples of up to 1 ml from individuals of an Egyptian Vulture colony in Spain.


Recurrence After Colectomy for Locally Advanced Colon Cancer: Experience from a Developing Country.
Risk factors for disease recurrence following curative resection for locally advanced colon cancer (LACC) remain unclear as conflicting results have been reported in the literature. The aim of this study was to examine these factors in the setting of developing country's health care system affected by limited accessibility to the multimodal cancer treatment. Patients who had undergone curative colon resection for LACC between 2004 and 2018 were included. Data were obtained from a prospectively maintained database. Factors associated with disease recurrence, types of recurrence and recurrence-free survival were studied. A total of 118 patients with LACC were operated within the study period. Median follow-up was 36 (2-147) months. Adjuvant therapy was used in 41 (34.7%) patients and 62 (52.5%) were diagnosed with recurrence. In the multivariable analysis, disease recurrence was associated with tumor and nodal stages, as well as with the lymph node yield. Local recurrence, distant metastases, and peritoneal carcinomatosis were observed in 8 (6.8%), 30 (25.4%), and 24 (20.3%) patients, respectively. Early recurrence was diagnosed in 27 (22.9%) cases with peritoneal carcinomatosis being its most common type. Preoperative serum CA 19-9 levels, tumor, and nodal stages were linked to recurrence-free survival in the univariable analysis. Only tumor stage remained such in the multivariable model. Our findings suggest that lymph node yield, tumor, and nodal stages are associated with recurrence following curative resection for LACC. The online version contains supplementary material available at 10.1007/s13193-022-01672-x.


Automated morphometry toolbox for analysis of microscopic model organisms using simple bright-field imaging.
Model organisms with compact genomes, such as yeast and C aenorhabditis elegans, are particularly useful for understanding organism growth and life/cell cycle. Organism morphology is a critical parameter to measure in monitoring growth and stage in the life cycle. However, manual measurements are both time consuming and potentially inaccurate, due to variations among users and user fatigue. In this paper we present an automated method to segment bright-field images of fission yeast, budding yeast, and C. elegans roundworm, reporting a wide range of morphometric parameters, such as length, width, eccentricity, and others. Comparisons between automated and manual methods on fission yeast reveal good correlation in size values, with the 95% confidence interval lying between -0.8 and +0.6 μm in cell length, similar to the 95% confidence interval between two manual users. In a head-to-head comparison with other published algorithms on multiple datasets, our method achieves more accurate and robust results with substantially less computation time. We demonstrate the method's versatility on several model organisms, and demonstrate its utility through automated analysis of changes in fission yeast growth due to single kinase deletions. The algorithm has additionally been implemented as a stand-alone executable program to aid dissemination to other researchers.


Stochastic Processes Dominate in the Water Mass-Based Segregation of Diazotrophs in a High Arctic Fjord (Svalbard).
Nitrogen-fixing or diazotrophic microbes fix atmospheric nitrogen (N2) to ammonia (NH3+) using nitrogenase enzyme and play a crucial role in regulating marine primary productivity and carbon dioxide sequestration. However, there is a lack of information about the diversity, structure, and environmental regulations of the diazotrophic communities in the high Arctic fjords, such as Kongsfjorden. Here, we employed nifH gene sequencing to clarify variations in composition, community structure, and assembly mechanism among the diazotrophs of the salinity-driven stratified waters of Kongsfjorden. The principal environmental and ecological drivers of the observed variations were identified. The majority of the nifH gene sequences obtained in the present study belonged to cluster I and cluster III nifH phylotypes, accounting for 65% and 25% of the total nifH gene sequences. The nifH gene diversity and composition, irrespective of the size fractions (free-living and particle attached), showed a clear separation among water mass types, i.e., Atlantic-influenced versus glacier-influenced water mass. Higher nifH gene diversity and relative abundances of non-cyanobacterial nifH OTUs, affiliated with uncultured Rhizobiales, Burkholderiales, Alteromonadaceae, Gallionellaceae (cluster I) and uncultured Deltaproteobacteria including Desulfuromonadaceae (cluster III), were prevalent in GIW while uncultured Gammaproteobacteria and Desulfobulbaceae were abundant in AIW. The diazotrophic community assembly was dominated by stochastic processes, principally ecological drift, and to lesser degrees dispersal limitation and homogeneous dispersal. Differences in the salinity and dissolved oxygen content lead to the vertical segregation of diazotrophs among water mass types. These findings suggest that water column stratification affects the composition and assembly mechanism of diazotrophic communities and thus could affect nitrogen fixation in the Arctic fjord.


Detection of the MUC2 apomucin tandem repeat with a mouse monoclonal antibody.
The MUC2 intestinal mucin gene contains tandem repeats of 23 amino acid length that are rich in threonine. Mouse monoclonal antibody LDQ10 was raised against chemically deglycosylated mucin isolated from LS174T colon cancer nude mouse xenografts. LDQ10 reacts with deglycosylated colon cancer mucin and with a synthetic peptide encompassing the MUC2 tandem repeat sequence. In immunohistochemical assays, strong reactivity with goblet cells in colon, small bowel, and stomach is observed; weaker reactivity with mucin-producing cells in other epithelial tissues is shown. The epitope recognized by LDQ10 is localized in the rough endoplasmic reticulum of normal colonic goblet cells. LDQ10 also shows strong reactivity with colorectal and stomach cancers and weaker reactivity with pancreas, breast, and bladder cancers. Antibody LDQ10 detects a peptide epitope of MUC2 that becomes cryptic on glycosylation. Altered synthesis of the MUC2 apomucin takes place in a variety of epithelial cancers.


Electroencephalographic investigations in sellar tumours, with special regard to different methods of operative treatment.
Sixty-six patients with tumours in the sellar region were examined. All were operated on either by the transfrontal or the transsphenoidal route. Pre- and postoperative longitudinal electroencephalographic investigations were performed. Preoperative electroencephalograms showed a normal frequency content in cases of intrasellar tumours or those reaching the chiasma. Nearly all cases had irregularities in the temporal regions. Tumours compressing the third ventricle had slower average frequencies and a general slowing in all cases. Besides these alterations unilateral delta waves or bitemporal dysrhythmic groups were sometimes found. A connection between extension of the tumour and its histological nature could not be found, but the operative approach influenced the electroencephalographic disturbances enormously. After a transfrontal approach and removal of the tumour the electroencephalogram was unchanged. Sometimes a mild transient bitemporal slowing was present. But after a transfrontal operative approach a general slowing was common, usually with focal marked slow activity in the right fronto-temporal area.


Bilateral adrenal hemorrhage after hip arthroplasty: an initially misdiagnosed case.
Bilateral adrenal hemorrhage (BAH) is a rare but potentially catastrophic condition. Its clinical manifestation is often non-specific and sometimes difficult to be diagnosed in time. A 57-year-old woman, who presented with severe fatigue, nausea and vomiting after left hip arthroplasty due to her femoral neck fracture in a local hospital, was transferred to our medical center. Laboratory results revealed significant hyponatremia, low serum cortisol and elevated serum ACTH. Computed tomography (CT) showed a bilateral adrenal mass, measured 3.6 × 2.7 cm on the left and 3.4 × 2.3 cm on the right. Further magnetic resonance imaging (MRI) confirmed the diagnosis of BAH. The patient was prescribed with oral prednisolone acetate, 5 mg, tid, and her condition improved gradually. Nine months after, the patient was in good condition with 5 mg prednisolone acetate per day. CT revealed a clearly shrunken adrenal mass compared with 9 months ago. This case illustrates the difficulty in making the diagnosis of BAH with atypical presentation. Such cases necessitate greater alertness on the part of the clinician and require rapid diagnosis and prompt glucocorticoid replacement for better clinical outcomes.


Trial of labour following prior section; a 5 year prospective study (1982-1987).
Between 1982 and 1987, 506 women previously delivered by Caesarean section were subjected to a trial of labour. Vaginal delivery was achieved in 78.6% with only 1 true rupture of the scar (0.2%). There were no intrapartum or neonatal deaths. Moreover, 7 of the 8 antepartum stillbirths were due to asphyxia, and, as the perinatal mortality rate for the study group was higher than for the overall population, the need for antenatal surveillance in previously sectioned patients is emphasized. Induction of labour was performed in 127 patients with 74.1% achieving vaginal delivery. Oxytocin was administered to 162 patients for either induction or augmentation of labour and 80.3% had a vaginal delivery, with 1 true rupture and 4 bloodless dehiscences. It is concluded that trial of labour following prior section is associated with little risk of true rupture, and with no added risk to the fetus. Our policy and management has helped maintain over the past 5 years an overall moderate Caesarean section rate (10-11%) with a low perinatal mortality rate.


Alfentanil and fentanyl sedation in infants and small children during cardiac catheterization.
Thirty patients aged 1-23 mth received either alfentanil or fentanyl for the induction and maintenance of IV sedation during cardiac catheterization following oral flunitrazepam premedication (0.1 mg.kg-1). Patients breathed spontaneously 30 per cent oxygen in air. Both alfentanil and fentanyl abolished all reaction to pain and discomfort with minimal haemodynamic and respiratory changes. Induction doses of alfentanil and fentanyl were 20 +/- 6 and 2.5 +/- 1.1 (mean +/- SD) micrograms.kg-1, respectively, and maintenance requirements 30 +/- 12 and 1.5 +/- 0.6 micrograms.kg-1.h-1, respectively. These requirements were comparable among younger and older as well as cyanotic and acyanotic patients. The IV sedation described adds an effective method to the armamentarium of an anaesthetist working in the cardiac laboratory.


Serum and urinary biomarkers to predict acute kidney injury in premature infants: a systematic review and meta-analysis of diagnostic accuracy.
Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants. A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria. We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58-89%), specificity of 76% (95% CI 57-88%) and AUC-SROC of 0.83 (95% CI 0.80-0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37-66%) with a positive test and decreased to 9% (95% CI 5-16%) with a negative test if the pre-test probability was 25%. uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants.


Cbx4 governs HIF-1α to involve in Th9 cell differentiation promoting asthma by its SUMO E3 ligase activity.
The potential role of polycomb chromobox 4 (Cbx4), as a small ubiquitin-like ligase (SUMO) E3 ligase, in the development and exacerbation of asthma remains unclear. Hypoxia inducible factor-1 (HIF-1) is a key transcription factor in the cellular response to hypoxia and contributes to the pathogenesis and progression of a range of diseases, including asthma. Here, we aimed to investigate the interaction of Cbx4 with Hypoxia inducible factor-1α (HIF-1α) and the potent mechanism of action in asthma progression. In present study, in vitro and ex vivo results demonstrated that Cbx4 interacts with HIF-1α protein through its SUMO E3 ligase activity and enhances the sumoylation, which increases HIF-1 transactivation through Cbx4 and promotes the differentiation of Th9 cells, then in turn promotes the process of asthma. Treatment of inhibitors targeting SUMO E3 ligase activity of Cbx4 or HIF-1α can effectively reduce HIF-1α activation and differentiation of Th9 cells, which further attenuates the asthma in mouse model. Current results collectively demonstrated Cbx4 can govern HIF-1α to involve in Th9 cell differentiation promoting asthma by its SUMO E3 ligase activity, providing a new direction for clinical treatment of asthma.


Effect of long-term antihypertensive therapy with angiotensin converting enzyme inhibitors on red cell sodium transport.
Several sodium transport abnormalities have been reported in erythrocytes from essential hypertensive patients. The possible modification of these parameters under antihypertensive treatment remains controversial. We have measured the maximal rates of the Na+/K+ pump, Na+/K+/Cl- cotransport, and Na+/Li+ countertransport and the rate constant of Na+ leak in erythrocytes from 22 essential hypertensive patient responders to angiotensin converting enzyme inhibitors quinapril or captopril, and from 17 patient nonresponders to these drugs. In the former group, sodium transport measurements were performed at the baseline placebo period and after 6 months of active treatment. The maximal rate of Na+/Li+ countertransport decreased significantly after 6 months of treatment, without differences between both groups of treatment. Angiotensin converting enzyme inhibitors did not significantly modify other sodium transport parameters. The basal activity of erythrocyte sodium transport was not different between patients who responded or not to antihypertensive treatment with those drugs, excluding a predictive value of these measurements concerning the response to angiotensin converting enzyme inhibitors.


Influence of experimental parameters on spatial phase distribution in as-sprayed and incubated hydroxyapatite coatings.
In the present study, the behavior and properties of plasma-sprayed hydroxyapatite coatings [Ca(10)(PO(4))(6)(OH)(2), HAp] were investigated in relation to the spraying process. The experiments were focused on the influence of type of feedstock and spray power on the phase composition and distribution within the coatings. Depth profiles of the coatings were investigated before and after incubation in revised simulated body fluid (SBF) by X-ray diffraction and infrared spectroscopy. Besides HAp, the coatings contain oxyapatite (OAp) and carbonate apatite (CAp). Additionally, tricalcium phosphate (TCP), tetracalcium phosphate (TTCP), CaO, and an amorphous phase were detected in the coatings. The HAp content directly depends on the used spray powder and spray power, where the influence of spray powder is much higher than the influence of the spray power. The grain size range of the spray powder strongly influences the HAp content in the coating and the formation of CaO. The in vitro behavior of the coatings in simulated body fluid mainly depends on the contents of CaO and amorphous calcium phosphate, respectively. The formation of portlandite due to the reaction of the coating with the SBF is strongly influenced by the porosity of the coatings and can be used as an indicator for the depth of interaction between fluid and coating.


Hypothalamo-pituitary hypothyroidism detected by neonatal screening for congenital hypothyroidism using measurement of thyroid-stimulating hormone and thyroxine.
The optimal strategy in neonatal screening for congenital hypothyroidism is still a subject of controversy. In Kanagawa Prefecture in Japan, simultaneous thyroid-stimulating hormone (TSH) and T4/fT4 determination has been used, while the results of our program may provide valuable information. Cumulative findings were analysed to determine the type and frequency of thyroid disorders in infants detected by simultaneous TSH and T4/fT4 determination, and the TSH and T4/fT4 screening strategy was validated. A total of 1284130 neonates were screened between October 1979 and September 1997 and infants followed because of low T4/fT4 without elevated TSH (T4 < 51.5 nmol/L or fT4 < 9 pmol/L and TSH < 15 mU/L) were retrospectively analysed. The first survey was carried out within 6 mo of birth and the second in 1998; 258 infants were diagnosed with congenital hypothyroidism at the first medical evaluation, 15 of them with hypothalamo-pituitary hypothyroidism. However, in the second survey, only 8 children were confirmed as having hypothalamo-pituitary hypothyroidism, therefore the incidence detected by the present strategy was 1/160516. Of 8 children with hypothalamo-pituitary hypothyroidism, mental retardation was prevented in 3 owing to early treatment. Simultaneous measurement of TSH and T4/fT4 is a useful strategy for detecting hypothalamo-pituitary hypothyroidism, but more studies are needed to show the cost-benefits of using this strategy.


Reconstruction of the face by means of the angle-rotation flap.
This article deals with defects in the face. A cervical flap called the angle-rotation flap was created by Schrudde 16 years ago to cover defects such as scarred skin after deep burn injuries as well as skin and subcutaneous defects following removal of dysplastic skin or after accidents. Indications and the method are described.


The Role of Anticoagulation in a Patient with Atrial Fibrillation and a CHADS2 Score of 1.
The CHADS2 score is currently the most widely used stroke risk stratification scheme for identifying patients with atrial fibrillation (AF) at low and high risk of stroke, but there is controversy over how to treat those patients whom it identifies as at intermediate risk. This review summarizes current risk scores and discusses additional markers for risk, including echocardiographic parameters, AF subtype, and AF burden, that may provide further insight into thromboembolism risk in patients with indeterminant risk (CHADS2 1).


The activity of flavone acetic acid (NSC 347512) on human colon cancer cells in vitro.
Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentrations of 250 micrograms/ml but no further increments in cytotoxicity were elicited when the concentration of FAA was augmented. Increasing the length of treatment yielded relatively modest increments (about 1 log) in cell killing only after an interval of 48 hr and only at the highest concentration (1000 micrograms/ml). Because of these relatively poor cytotoxic effects and because the therapeutic range of FAA is so narrow, we conclude that this agent will not be a valuable contribution to the antitumor arsenal, at least for colon cancer.


Evaluation of oral health related to body mass index.
Poor oral health has previously been related to high body mass index (BMI). We aimed at exploring the link between BMI and several oral health markers, after adjustment for dietary patterns and plasma insulin, both of which could act as mediators. Dental examination was performed in a sample of 186 French subjects aged 35-64 years and selected from the general population to assess number of missing teeth, periodontitis, clinical attachment loss (CAL), probing pocket depth (PD), gingival index (GI) and plaque index (PI). Data collection also included a food-frequency questionnaire. BMI (considered as outcome variable) was categorized into quartiles, and as BMI<25; 25 ≤BMI<30; and BMI ≥ 30 kg m(-2) . After adjustment for age, gender, education level, smoking, physical activity, energy intake and C-reactive protein, BMI was statistically associated with missing teeth, PD and PI, but not with CAL, GI or periodontitis. After additional adjustment for 'high-carbohydrate' diet and plasma insulin or HOMA (homeostasis model assessment) index for insulin resistance, the statistical relationship between BMI and oral variables remained significant only for PD and PI. Plaque index, reflecting dental plaque, and PD, closely linked with periodontal inflammation and infection, are statistically associated with high BMI and obesity, independently of dietary patterns and insulin resistance.


Increased metabolic clearance of acetaminophen with oral contraceptive use.
The effect of chronic low-dose oral contraceptive steroid use on the pharmacokinetics of intravenous acetaminophen was determined. Eight women using low-dose (under 50 micrograms) estrogen oral contraceptive steroid for more than 3 months were matched for age and weight (mean age, 25.9 years; mean weight, 58.3 kg) with 8 female controls not using the steroid (mean age, 26.0 years; mean weight, 55.5 kg). No subject was taking other drugs. Oral contraceptive steroid subjects had a lower elimination half-life of acetaminophen (2.12 hours) than controls (2.71 hours) (P less than .005). Volume of distribution was similar for both groups (oral contraceptive group, 1.04 liters/kg; controls, 0.96 liters/kg; NS). Total metabolic clearance was significantly higher in oral contraceptive subjects (5.81 ml/min/kg, versus 4.12 ml/min/kg for controls; P less than .02). As volume of distribution and body weight are similar for both groups, the decrease in acetaminophen elimination half-life among contraceptive steroid users is the result of increased total metabolic clearance. Thus, low-dose estrogen oral contraceptive steroid may stimulate the metabolism of a conjugatively metabolized drug such as acetaminophen, in contrast to contraceptive steroid impairment of the clearance of some oxidatively metabolized drugs, with antipyrine being the prototype.


Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells.
Exposure to exogenous and endogenous sources cause oxidative damage to cellular macromolecules, including DNA. This results in gradual accumulation of oxidative DNA base lesions, and in order to maintain genomic stability we must have effective systems to repair this kind of damage. The accumulation of lesions is most dramatic in the mitochondrial DNA, and this may cause dysfunction and loss of cellular energy production. Base excision DNA repair (BER) is the major pathway that removes oxidative DNA base lesions, and while we know much about its mechanism in the nuclear DNA, little is yet known about this pathway in mitochondria. While nuclear BER decreases with age, the mitochondrial DNA repair may increase with age. This increase is not enough to prevent the gradual accumulation of lesions in the mitochondrial DNA with age. Accumulation of DNA lesions with age may be the underlying cause for age-associated diseases including cancer.


Discriminating between natural and anthropogenic earthquakes: insights from the Emilia Romagna (Italy) 2012 seismic sequence.
The potential for oilfield activities to trigger earthquakes in seismogenic areas has been hotly debated. Our model compares the stress changes from remote water injection and a natural earthquake, both of which occurred in northern Italy in recent years, and their potential effects on a nearby Mw 5.9 earthquake that occurred in 2012. First, we calculate the Coulomb stress from 20 years of fluid injection in a nearby oilfield by using a poroelastic model. Then, we compute the stress changes for a 2011 Mw 4.5 earthquake that occurred close to the area of the 2012 mainshock. We found that anthropogenic activities produced an effect that was less than 10% of that generated by the Mw 4.5 earthquake. Therefore, the 2012 earthquake was likely associated with a natural stress increase. The probability of triggering depends on the magnitude of recent earthquakes, the amount of injected water, the distance from an event, and the proximity to the failure of the activated fault. Determining changes that are associated with seismic hazards requires poroelastic area-specific models that include both tectonic and anthropogenic activities. This comprehensive approach is particularly important when assessing the risk of triggered seismicity near densely populated areas.


Rheumatic involvement and bone scan features in Schnitzler syndrome: initial and follow-up data from a single-center cohort of 25 patients.
To report on the characteristics and long-term course of rheumatic manifestations in Schnitzler syndrome (SchS). A retrospective cohort study of patients with SchS followed between 2000 and 2020. Inclusion criteria included a diagnosis of SchS (Strasbourg criteria). All available bone scans were reviewed and scored according to the intensity and number of pathological sites. The scintigraphic score was compared with the clinical activity score, CRP level, and treatments. Twenty-five patients were included. Median age at diagnosis was 68 years. Eighty patients (72%) had SchS-related rheumatic pain. Most patients had a long-standing isolated rash before constitutional and/or rheumatic symptoms appeared. The monoclonal component level was usually very low (IgMκ in 22/25). Rheumatic pain predominated around the knees. Bone scans revealed abnormal tracer uptake in 15/18 (85%). The scintigraphic score correlated with clinical activity (r = 0.4, p < 0.02) and CRP level (r = 0.47, p < 0.01). The scintigraphic score was lower in patients receiving corticosteroids or IL1Ra (interleukin 1 receptor antagonist) than in untreated patients (median scores:2, 0, and 13, respectively; p < 0.05). Two patients developed Waldenström macroglobulinemia. Of the 22 surviving patients, median age at follow-up was 76 years. IL1Ra was used in 13 patients, with dramatic efficacy on both symptoms and bone scan features. Rheumatic manifestations are very prevalent in SchS. However, bone pain can be misleading and contribute to misdiagnosis. Bone scan abnormalities are very prevalent and correlate with disease activity and treatments. IL1-Ra has a dramatic and durable efficacy but may not be required in every patient early on.


Bacillary Detachment in Neovascular Age-Related Macular Degeneration: Incidence, Clinical Features, and Response to Anti-VEGF Therapy.
To evaluate the incidence of bacillary layer detachment among patients with neovascular age-related macular degeneration (nAMD) and their response to anti-VEGF therapy. Post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase II study comparing 6-mg brolucizumab with 2-mg aflibercept over 56 weeks. Participants with treatment-naive nAMD at the initiation of the trial were included in the analysis (n = 81). Spectral-domain OCT (SD-OCT) scans were obtained at 4-week intervals throughout the OSPREY study and were segmented automatically using a proprietary, machine learning-enabled higher-order feature-extraction platform. The presence of bacillary detachment, and in these eyes the effect of anti-VEGF therapy on change from baseline in visual acuity (VA), central subfield thickness (CST), retinal fluid volumes, subretinal hyper-reflective material (SHRM) volume, subretinal pigment epithelium (sub-RPE) fluid volume, and ellipsoid zone (EZ) integrity at week 56. Bacillary detachment was identified in 7.4% (6 of 81) eyes, which had higher fluid volumes, increased CST, EZ attenuation, and increased sub-RPE volume at baseline compared with eyes without bacillary detachment. Anti-VEGF treatment resulted in the resolution of bacillary detachment in 100% of the eyes. In eyes with bacillary detachment at baseline, the anti-VEGF treatment decreased CST, fluid burden, and SHRM volumes throughout the treatment course; however, there was no significant change from baseline in VA, sub-RPE volume, or EZ integrity throughout the 56-week course of anti-VEGF treatment. Bacillary detachment is an OCT signature that is identifiable in a notable proportion of nAMD eyes. Anti-VEGF therapy resulted in 100% resolution of bacillary detachment and significant decreases in CST and SHRM volume; however, improvements in VA may have been limited by persistent EZ attenuation.


Overlapping and Non-overlapping Practices in Usual and Evidence-Based Care for Youth Anxiety.
This study compared consistencies and discrepancies in usual care with practices derived from the evidence-base (PDEB) for youth anxiety in a public mental health system. Youth-level factors (diagnosis, functional impairment) as predictors of the discrepancies were also examined. Psychosocial and service data from 2485 youth with an anxiety disorder and/or receiving services for an anxiety treatment target were extracted. Therapists (N = 616) identified the treatment targets and practices youth received. Although many PDEB for youth anxiety were used by therapists in this sample, Exposure was only used in 15% of cases. Practices not consistent with youth anxiety treatment were also reported and included: PDEB for other conditions, practices common to all therapies, and practices that are not consistent with evidence-based care. Age and diagnosis predicted the delivery of PDEB for youth anxiety. Usual care incorporated many components of evidence-based care but was more diffuse and less focused on well-supported practices.


Gastric permeability is not increased in children colonized by CagA-positive strains of Helicobacter pylori.
Sucrose permeability has been used as a marker to detect gastric lesions in children. As CagA status of Helicobacter pylori is an important factor in determining the evolution of the gastric lesion, CagA-positive strains being more frequently associated with severe mucosal lesions, the aim of this study was to determine the prevalence of CagA-positive strains in Helicobacter pylori-colonized children and to evaluate whether the sucrose permeability test might discriminate between colonization by CagA-positive or negative strains. A series of 38 children (11.1+/-3.6 years) who required upper endoscopy for diagnostic purposes were included in the study. Endoscopy was carried out after the sucrose permeability test, and gastric biopsies were obtained for histologic examination, Helicobacter pylori detection by Giemsa staining and CLO-test, and determination of CagA status of the colonizing Helicobacter pylori strains by polymerase chain reaction. Helicobacter pylori was detected in 26 subjects (68.4%) and of these, 16 (61.5%) were colonized by CagA-positive strains. The intensity of the histologic findings was significantly associated with the presence of Helicobacter pylori and with CagA status of the infecting strains (chi2=21.2, p=0.0017). However no significant difference in the urinary excretion of sucrose between children not colonized and children with CagA- negative or positive strains was observed (0.027% [0.012-0.035%]; 0.027% [0.016-0.047%] and 0.026% [0.016-0.038], median [range], respectively; Kruskal-Wallis analysis of variance F=0.75, p=0.69). These results indicate that in Chile, about 60% of the Helicobacter pylori infected children are colonized by CagA-positive strains, in association with more intense lesions of the gastric mucosa, but that gastric permeability to sucrose does not discriminate between colonization by CagA-negative and positive strains of Helicobacter pylori.


Racial and ethnic differences in circulating N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in US adults.
The presence and interpretation of racial and ethnic differences in circulating N-terminal pro-brain-type natriuretic peptide (NT-proBNP), a diagnostic biomarker for heart failure, are controversial. To examine racial and ethnic differences in NT-proBNP levels among the general US adult population. We performed a cross-sectional analysis of data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). We included 4717 non-Hispanic White, 1675 non-Hispanic Black, and 2148 Mexican American adults aged 20 years or older without a history of cardiovascular disease. We examined the associations of race and ethnicity with NT-proBNP using linear and logistic regression models in the overall population and in a younger, 'healthy' subsample. The mean age was 45 years. Median NT-proBNP levels were significantly lower among Black (29.3 pg/mL) and Mexican American adults (28.3.4 pg/mL) compared to White adults (49.1pg/mL, P-values<0.001). After adjusting for sociodemographic factors and cardiovascular risk factors, NT-proBNP was 34.4% lower (95%CI -39.2 to -29.3%) in Black adults and 22.8% lower (95%CI -29.4 to -15.5) in Mexican American adults compared to White adults. Our findings were consistent in a young, healthy subsample, suggesting non-cardiometabolic determinants of these differences. NT-proBNP levels are significantly lower among Black and Mexican American adults compared with White adults, independent of cardiometabolic risk. Although race/ethnicity is a poor proxy for genetic differences, our findings may have clinical implications for the management of HF. However, studies in diverse populations are needed to characterize the biological basis of NT-proBNP variation.


Sarcoplasmic reticulum Ca(2+)-ATPase of sea cucumber smooth muscle: regulation by K(+) and ATP.
Although several Ca(2+)-ATPase isoforms have been described in vertebrates, little is known about Ca(2+)-transport in the muscle of invertebrates. In the microsomal fraction obtained from the sea cucumber (Ludwigothurea grisea) longitudinal body wall smooth muscle, we identified a Ca(2+)-transport ATPase that is able to transport Ca(2+) at the expense of ATP hydrolysis. This enzyme has a high affinity for both Ca(2+) and ATP, an optimum pH around 7.0, and - different from the vertebrate sarcoplasmic reticulum Ca(2+)-ATPases isoforms so far described - is activated 3- to 5-fold by K(+) but not by Li(+), at all temperatures, Ca(2+) and ATP concentrations tested. Calcium accumulation by the sea cucumber microsomes is inhibited by Mg/ATP concentrations >1 mM and the accumulated Ca(2+) is released to the medium when the ATP concentration is raised from 0.1 to 4.0 mM.


[Combination chemotherapy including cis-platinum in Ewing's sarcoma].
A clinical study of cis-platinum was conducted on 5 patients with Ewing's sarcoma. Cis-platinum was preoperatively administered at doses of 70-100 mg/m2. Good response on imaging diagnosis was recorded in all cases. With regard to side effects, 2 of the 5 patients suffered from hearing loss, but only slight bone marrow suppression was observed. We concluded that cis-platinum was effective for the preoperative treatment of Ewing's sarcoma.


A gonococcal homologue of meningococcal gamma-glutamyl transpeptidase gene is a new type of bacterial pseudogene that is transcriptionally active but phenotypically silent.
It has been speculated that the gamma-glutamyl transpeptidase (ggt) gene is present only in Neisseria meningitidis and not among related species such as Neisseria gonorrhoeae and Neisseria lactamica, because N. meningitidis is the only bacterium with GGT activity. However, nucleotide sequences highly homologous to the meningococcal ggt gene were found in the genomes of N. gonorrhoeae isolates. The gonococcal homologue (ggt gonococcal homologue; ggh) was analyzed. The nucleotide sequence of the ggh gene was approximately 95% identical to that of the meningococcal ggt gene. An open reading frame in the ggh gene was disrupted by an ochre mutation and frameshift mutations induced by a 7-base deletion, but the amino acid sequences deduced from the artificially corrected ggh nucleotide sequences were approximately 97% identical to that of the meningococcal ggt gene. The analyses of the sequences flanking the ggt and ggh genes revealed that both genes were localized in a common DNA region containing the fbp-ggt (or ggh)-glyA-opcA-dedA-abcZ gene cluster. The expression of the ggh RNA could be detected by dot blot, RT-PCR and primer extension analyses. Moreover, the truncated form of ggh-translational product was also found in some of the gonococcal isolates. This study has shown that the gonococcal ggh gene is a pseudogene of the meningococcal ggt gene, which can also be designated as Psiggt. The gonococcal ggh (Psiggt) gene is the first identified bacterial pseudogene that is transcriptionally active but phenotypically silent.


Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil.
Lipid nanoparticles of the cancer drug Chlorambucil (CLB) were prepared by ultrasonication, using stearic acid as the core lipid. Four types of lipid nanoparticle formulations were studied: (i) stearic acid solid lipid nanoparticles (SLN); (ii) sterically stabilized SLN with pegylated phospholipids as stabilizer; (iii) nanostructured lipid complexes with oleic acid as adjunct lipid; (iv) lipid nanocomplexes with dimethyl dioctadecyl ammonium bromide (DDAB) as surface modifier (LN). Lipid nanoparticles were characterized for particle size, assay and encapsulation efficiency, particle morphology and physico-chemical stability over 90 days. All of the formulations were physically stable, with an average particle size of 147 (+/-10)nm. The drug encapsulation efficiency (DEE) of all the formulations except LN decreased significantly over time (p<0.05), probably due to the expulsion of CLB upon crystallization. This indicated that the presence of DDAB in stearic acid nanoparticles increases DEE, preventing CLB degradation in the aqueous disperse phase. Pharmacokinetic studies of the intravenous LN formulation revealed plasma clearance kinetics were comparable to that of CLB solution (p>0.01), indicating electrostatic charge mediated clearance, as reported earlier. In tissue and tumor distribution studies, lower AUC values of CLB were observed for LN compared to CLB solution in liver, kidneys, heart and lungs. However, higher AUC values of LN formulation as compared to CLB solution (p<0.01) in tumors suggested that the presence of DDAB on the lipid nanoparticles resulted in greater accumulation of the drug in tumors.


The impact of fasting on resting state brain networks in mice.
Fasting is known to influence learning and memory in mice and alter the neural networks that subserve these cognitive functions. We used high-resolution functional MRI to study the impact of fasting on resting-state functional connectivity in mice following 12 h of fasting. The cortex and subcortex were parcellated into 52 subregions and functional connectivity was measured between each pair of subregions in groups of fasted and non-fasted mice. Functional connectivity was globally increased in the fasted group compared to the non-fasted group, with the most significant increases evident between the hippocampus (bilateral), retrosplenial cortex (left), visual cortex (left) and auditory cortex (left). Functional brain networks in the non-fasted group comprised five segregated modules of strongly interconnected subregions, whereas the fasted group comprised only three modules. The amplitude of low frequency fluctuations (ALFF) was decreased in the ventromedial hypothalamus in the fasted group. Correlation in gamma oscillations derived from local field potentials was increased between the left visual and retrosplenial cortices in the fasted group and the power of gamma oscillations was reduced in the ventromedial hypothalamus. These results indicate that fasting induces profound changes in functional connectivity, most likely resulting from altered coupling of neuronal gamma oscillations.