Genetic variability among ampC genes from acinetobacter genomic species 3.
As a part of a nationwide study in Spain, 15 clinical isolates of Acinetobacter genomic species 3 (AG3) were analyzed. The main objective of the study was to characterize the ampC genes from these isolates and to determine their involvement in beta-lactam resistance in AG3. The 15 AG3 isolates showed different profiles of resistance to ampicillin (range of MICs, 12 to >256 microg/ml). Nucleotide sequencing of the 15 ampC genes yielded 12 new AmpC enzymes (ADC-12 to ADC-23). The 12 AG3 enzymes showed 93.7 to 96.1% amino acid identity with respect to the AmpC enzyme from Acinetobacter baumannii (ADC-1 enzyme). Eight out of fifteen ampC genes were expressed in Escherichia coli cells under the control of a common promoter, and with the exception of one isolate (isolate 65, which showed lower beta-lactam MICs), significant differences in overall beta-lactam MICs for E. coli cells expressing AG3 ampC genes were not revealed. No significant differences in ampC gene expression in AG3 clinical isolates were revealed by reverse transcription-PCR analysis. A detailed analysis of the 12 AmpC protein sequences revealed that amino acid replacements (in comparison with those of ADC-1) occurred mainly in the same positions, although none were located in important functional domains such as the Omega- loop or conserved beta-lactamase motifs. Kinetic experiments performed with three representative AmpC enzymes (ADC-14, -16, and -18) in some cases revealed dramatic changes in K(m) and k(cat) values for beta-lactams. No ISAba1 was detected upstream of the ampC genes. Our results reveal 12 new ampC genes in AG3. The enzymes showed a moderate degree of variability, and they are tentatively named ADC-12 to ADC-23.


ON THE ORIGIN OF INCIPIENT REPRODUCTIVE ISOLATION: THE CASE OF DROSOPHILA ALBOMICANS AND D. NASUTA.
The nasuta subgroup of Drosophila consists of 12 known species classified within the immigrans group. D. nasuta and D. albomicans are two sibling species widely distributed throughout the Indo-Pacific tropics, which, although morphologically indistinguishable, have different meta-phase-chromosome configurations: chromosomes X and 3 are attached in D. albomicans, so that about 60% of its genes are sex-linked. Our experiments show that, at least in the laboratory, there is no sexual, mechanical, or gametic isolation between the two species. There is, however, hybrid "breakdown" expressed in three ways: 1) reduction in the number of F2 hybrids produced per culture; 2) reduction in the fertility of F2 (males) and F3 (males and females) hybrid progenies; and 3) abnormal sex ratios in the progenies of crosses between strains of certain localities. In experimental populations, the karyotypes of both species are still present in substantial frequencies after 20 generations, although the frequencies of the two karyotypes vary depending on the geographic origin of the strains. Our results support the hypothesis that, in allopatry, the evolution of postzygotic isolation precedes that of prezygotic isolation. The mtDNA is polymorphic in both D. nasuta and D. albomicans and fairly similar between them. Assuming typical rates of mtDNA evolution, the two species would have diverged from each other about 500,000 years ago, whereas the African and Indian populations of D. nasuta (considered to be different subspecies by some authors) might have diverged some 350,000 years ago.


Religiosty and Mental Health in Nursing Students.
Young people and nursing students are prone to stress and psychological consequences of it. The aim of the current study was to assess the associations between psychopathology and religiosity in the group of nursing university students. The study included 100 nursing students of the Faculty of Health Studies in Mostar. The participants were assessed with the SLC-90-R and Dimensions of Religiosity Questionnaire. Sociodemographic data were also collected. All SCL-90-R subscales negatively correlated with religiosity showing that the strength of religiosity was associated with better mental health of nursing students. Twenty two percent of potential cases of mental disorder were detected based on the GSI cut-off score. Religiosity was a significant predictor of mental disorder in logistic regression based on the GSI. The year of the study and quality of family relations were associated with students' religiosity. Gender, socioeconomic status and parents' education were associated with higher psychopathology scores. Religiosity showed to be important factor of resilience for nursing students. Further studies are needed.


Infection control surveillance in a rehabilitation hospital.
Infection control surveillance in a rehabitation setting is essential to quality assurance because of the high number of infection risk factors found in this patient population. These factors include longer length of stay, high incidence of urinary tract instrumentation, and high incidence of skin lesions, including decubital and stump wounds. A surveillance process is described which offers timely access to each infected patient's diagnosis, treatment, and follow-up, and results in simplified hospital-wide antibiotic monitoring. Quality assurance problems identified through this surveillance plan involved specimen collecting and reporting errors, nursing-procedure inadequacies, and organism misidentification. These and other examples illustrate the distinctive role an infection control program can play in quality monitoring and problem solving in a rehabilitation hospital.


Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.
The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, P<.001) and isolates from neutropenic patients (98.6% vs 62.8%, P < .001). In the antimicrobial susceptibility test, carbapenems and amikacin exhibited not only higher in vitro activity against E coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2.223; 95% CI 1.132-12.022; P < .01) and septic shock (OR 52.359; 95% CI 19.951-292.690; P = .030) were risk factors for death.In the hematology department, ESBL-producing and MDR are widely prevalent in E coli bacteremia which is still a major life-threatening problem, especially for patients with septic shock. For empirical antimicrobial therapy, combination based on aminoglycoside, especially amikacin, will be helpful to increase the antimicrobial coverage against ESBL-EC while combining tigecycline with aminoglycoside should be considered for seriously carbapenem-resistant infectious patients.


Early decrease in skin reactivity after rush venom immunotherapy.
Previous studies have documented changes in skin reactivity after specific immunotherapy. The aim of this study was to evaluate the time course of this phenomenon after rush venom immunotherapy. According to the method of endpoint evaluation, the skin reactivity of 38 patients allergic to venom was studied 24 h before and after the end of a rush venom immunotherapy protocol (7 days). The results were compared with 13 controls. An early significant decrease in skin reactivity was documented (p < 0.001), which was not related to an increase in specific IgG. Thus, rush venom immunotherapy induces a very early decrease in skin reactivity.


[A study on the active efflux mechanism in Staphylococcus aureus resistant to quinolone].
To explore the effect, the characteristic, and potential approaches to the active efflux mechanism in straphylococcus aureus (S. a) resistant to quinolones. S. a standard strain ATCC25923 and clinical isolates susceptible to quinolone were inoculated onto MH agar containing ofloxacin at a concentration of 4 x MIC (in the presence or absence of 20 micro g of reserpine/ml). Following incubation at 35 degrees C for 48 h, the inhibiting effect of reserpine on the occurrence of induced resistance was observed and the MIC of the induced resistant strain to ethidium bromide (EB), ofloxacin and ciprofloxacin (in the presence or absence of 20 micro g of reserpine/ml) was determined. The influence of reserpine to the MIC of induced resistant strains was also determined. The accumulation and loss of EB was determined based on the fact that EB's fluorescence can be strengthened when combined with DNA. Reserpine inhibition test was used to study the active efflux in clinical S. a resistant to quinolone. The active efflux mechanism in S. a resistant to second generation quinolones was confirmed by the reserpine's influence on the level of ethidium bromide (EB) in the cytoplasm of S. a. Reserpine reduced the 50 percent resistant rate to quinolone in induced resistant S. a, and decreased the MIC of induced resistant strains. Reserpine inhibited the active efflux of EB from the cytoplasm of S. a. Active efflux is an important mechanism in S. a resistant to quinolone. Reserpine can inhibit its active efflux mechanism, and has synergistic effect with quinolone, which hold therapeutic potential for S. a resistant to quinolones.


Zinc-Catalyzed Asymmetric Cascade Michael/Acyl Transfer Reaction between α-Hydroxy Aryl Ketones and Enynones.
We described herein a neoteric enantioselective cascade Michael/acyl transfer reaction of enynones and α-hydroxy aryl ketones catalyzed by dinuclear zinc cooperative catalysis. A series of structurally diverse chiral 1,5-dicarbonyl compounds were synthesized in good yields with excellent stereoselectivities. This strategy features broad substrate scope, high atom economy, as well as enynones as efficient electrophilic acyl transfer reagents in asymmetric cascade reactions for the first time.


[Outpatient parenteral antibiotic therapy (OPAT)].
Traditionally, parenteral (i. e. intravenous) antimicrobial therapy has been used in inpatients with various bacterial infections. In recent decades there has been growing experience with outpatient parenteral antimicrobial therapy, mainly in the USA and western Europe. This article provides basic information on OPAT, based on available literature and the author´s experience on running OPAT service in the UK.


An automated coronary artery occlusion device for stimulating collateral development in vivo.
Repetitive, brief coronary artery occlusions produce collateral development in experimental animals. This model causes coronary collateralization in a highly reproducible fashion, but the process is very labor intensive. We report the design and use of a fully automated hydraulic coronary occlusion device capable of producing repetitive coronary occlusions and enhancement of coronary collateral development in dogs. The device consists of analog electronics that allow adjustment of occlusion number, frequency, pressure and duration, and mechanical components responsible for the coronary occlusion. The motor and piston of the device are coupled to a chronically implanted hydraulic vascular occluder placed around the left anterior descending coronary artery (LAD) of dogs instrumented for measurement of systemic and coronary hemodynamics. One group of dogs (n = 6) underwent brief (2 min) LAD occlusions once per hour, eight times per day, 5 days/week for 3 weeks to stimulate collateral development (measured using radioactive microspheres). Another group of dogs (n = 6) that did not receive repetitive occlusions served as controls. The device reproducibly produced repetitive LAD occlusions for the duration, frequency, and time interval initially programmed. A time-dependent increase in transmural collateral blood flow was observed in dogs undergoing repetitive occlusions using the device. Collateral blood flow was unchanged in dogs that did not undergo occlusions. The automated occluder device reliably produces repetitive coronary occlusions and may facilitate further study of coronary collateral development in response to chronic myocardial ischemia.


Dynamic Graph Cuts in Parallel.
This paper aims at bridging the two important trends in efficient graph cuts in the literature, the one is to decompose a graph into several smaller subgraphs to take the advantage of parallel computation, the other is to reuse the solution of the max-flow problem on a residual graph to boost the efficiency on another similar graph. Our proposed parallel dynamic graph cuts algorithm takes the advantages of both, and is extremely efficient for certain dynamically changing MRF models in computer vision. The performance of our proposed algorithm is validated on two typical dynamic graph cuts problems: the foreground-background segmentation in video, where similar graph cuts problems need to be solved in sequential and GrabCut, where graph cuts are used iteratively.


Biologic effects of interferons.
If one were to review articles on IFN published between 1957 and 1967 it would become apparent that virtually none of the tenets held then are still valid today. Whereas IFN was long considered to be a specific antiviral substance without any effect on normal cellular metabolism, we accept today that it affects normal cell division and many specialized cellular functions. In this respect it is not unique; IFN is a prototype of a family of similar substances now called cytokines that all appear to function as regulatory molecules. It was held that the production of IFN constituted a specific response to a viral infection. Today we believe that IFN is an integral part of a cytokine network and that they and other cytokines may be produced constitutively at low levels. These substances exert multiple effects on virtually all cells. They play an important role in host defense against viral and parasitic infections, and in the resistance to experimental tumors. IFN can be shown to exert effects on the immune system and on lymphocyte circulation. Lastly, because of the multiplicity of their biologic effects, they may even contribute to the pathogenesis of certain diseases. Thus, when large amounts of IFN are administered or induced in newborn mice they can cause liver, kidney, and pulmonary disease. The field of IFN and cytokine research continues to expand and there is an increasing number of therapeutic applications. Twenty years from now, scientists and clinicians may be surprised that we understood so little of how IFN act and how inadequately we used them to treat disease.


Investigation of an antitumor drug-delivery system based on anti-HER2 antibody-conjugated BSA nanoparticles.
Conjugation of a monoclonal antibody with a nanoparticle often improves its specificity and drug loading in cancer therapy. In this study, we prepared a novel targeting nanodrug-delivery system using 2-methoxy-estradiol (2-ME) based on anti-human epidermal growth factor receptor 2 (HER2) antibody-modified BSA to improve the clinical application and antitumor effect of 2-ME. 2-ME-loaded albumin nanoparticles (2-ME-BSANPs) were prepared using a desolvation method and the anti-HER2 antibodies were conjugated to 2-ME-BSANPs (HER2-2-ME-BSANPs) using the coupling agent, succinimidyl 3-(2-pyridyldithio)propionate. HER2-2-ME-BSANPs were characterized using SDS-polyacrylamide gel electrophoresis, an agglutination test, and an immunofluorescence assay. We found that mouse anti-human anti-HER2 monoclonal antibody was successfully conjugated to the 2-ME-BSANPs. Thereafter, the in-vitro and in-vivo toxicities were evaluated using two cancer cell lines, SK-BR-3 (HER2-overexpressing) and MCF-7 (HER2-underexpressing), using classic pharmacological methods and in-vivo imaging technology. We found that the HER2-2-ME-BSANPs retained the immunospecificity of the anti-HER2 monoclonal antibody, rapidly localized to HER2 receptors, and could be used for targeted cancer therapy.


Amplification of bifunctional ligands for calmodulin from a dynamic combinatorial library.
A well known strategy to prepare high affinity ligands for a biological receptor is to link together low affinity ligands. DCC (dynamic combinatorial chemistry) was used to select bifunctional protein ligands with high affinity relative to the corresponding monofunctional ligands. Thiol to disulfide linkage generated a small dynamic library of bifunctional ligands in the presence of calmodulin, a protein with two independently mobile domains. The binding constant of the bifunctional ligand (disulfide) most amplified by the presence of calmodulin is nearly two orders of magnitude higher than that of the corresponding monofunctional ligand (thiol).


lncRNAs AC156455.1 and AC104532.2 as Biomarkers for Diagnosis and Prognosis in Colorectal Cancer.
There have been countless studies to date assessing specific oncogenic pathways in a range of tumor classes, but the role of N6-methyladenosine- (m6A-) related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains to be defined. We analyzed such m6A-related lncRNAs by conducting analyses of the Pearson correlation with information originating from the databank of The Cancer Genome Atlas (TCGA). The prognostic relevance of these lncRNAs in CRC was then assessed through a series of univariate Cox regression analyses, leading to the identification of two different m6A modification patterns; they are associated with clinical outcomes and have been used to estimate tumor immune microenvironment (TIME) by the CIBERSORT and ESTIMATE algorithms. We tested the expression of m6A-related lncRNAs in twelve pairs of colorectal cancer tissues and adjacent normal tissues from patients by qRT-PCR. We discovered the prognostic risk signature composed of six m6A-related lncRNAs based upon TCGA data. When the overall survival of cases in the dataset of TCGA was investigated, the low-risk cases survived longer than the high-risk CRC cases in both the training and testing cohorts. ROC curves further indicated that m6A-related lncRNA prognostic signature (m6A-LPS) can effectively estimate the survival outcomes of patients in both of these cohorts. We found that lncRNAs AC156455.1 and AC104532.2 were upregulated in twelve colorectal cancer tissues compared with adjacent normal tissues using qRT-PCR. This data highlights that the lncRNAs AC156455.1 and AC104532.2 in CRC can be used as biomarkers for diagnostics and prognosis in CRC, demonstrating their potential as targets when designing novel immunotherapeutic regimens.


Longitudinal change in thigh muscle strength prior to and concurrent with symptomatic and radiographic knee osteoarthritis progression: data from the Osteoarthritis Initiative.
To investigate whether symptomatic and/or radiographic knee osteoarthritis (KOA) progression is associated with prior and/or concurrent change in thigh muscle strength in men or women. Osteoarthritis Initiative (OAI) participants with isometric muscle strength measurements at baseline, 2- and 4-year follow-up (n = 1785: 1016 women) were grouped into 1) those with vs without symptomatic progression (i.e., increase ≥9 in WOMAC-pain [scale: 0-100]); and 2) those with vs without radiographic progression (i.e., decrease in minimum joint space width (JSW) ≥0.7 mm) between year-two and year-four follow-up. Sex-specific changes in thigh muscle strength concurrent (between year-two and year-four follow-up) and prior to (between baseline and year-two follow-up) symptomatic and radiographic progression were compared between groups (progression vs no progression) using analysis of covariance, with adjustment for age and body mass index. In women, but not in men, loss in knee extensor and flexor strength was greater concurrent with symptomatic progression (extensors: -3.7%, 95% confidence interval [CI] -6.4, -0.9; flexors: -7.2% 95% CI -10.7, -3.7) than in women without symptomatic progression (extensors: -0.3%, 95% CI -1.9, 1.3, P = 0.030; flexors: -2.6%, 95% CI -4.7, -0.6, P = 0.018). No association was found between extensor or flexor strength loss concurrent to radiographic progression, in either men or women, nor any statistically significant association between prior change in muscle strength with symptomatic or radiographic progression. These findings suggest that there is concurrent but not prior longitudinal association between loss in muscle strength and symptomatic KOA progression that is specific to women.


Identification of a pyroptosis-related long non-coding RNA Signature for prognosis and its related ceRNA regulatory network of ovarian cancer.
Aim: To identify the pyroptosis-related long non-coding RNAs (lncRNAs) in ovarian cancer and construct a prognostic signature based on them. Methods: Expression data from TCGA was used to explore differentially expressed pyroptosis-related lncRNAs in ovarian cancer. A risk signature was established by LASSO and cox regression analysis and then validated. Databases such as ESTIMATE, CIBERSORT, TIMER, XCELL were used to identify the relation between this signature and the immune microenvironment of ovarian cancer. Gene Set Enrichment Analysis was introduced to identify the pathways and functions that the signature may participate in. Based on miRcode and starBase databases, microRNAs related to the lncRNAs in our signature and the positively co-expressed pyroptosis- related genes were screened and a competing endogenous RNA (ceRNA) network was then constructed. Quantitative reverse transcription PCR was conducted to validate the expression levels of two lncRNAs in this ceRNA network. Results: A 13 pyroptosis-related lncRNA prognostic signature (MYCNOS, AL161772.1, USP30-AS1, ZNF32-AS2, AC068733.3, AC012236.1, AC015802.5, KIAA1671-AS1, AC013403.2, MIR223HG, KRT7-AS, PTPRD-AS1 and LINC01094) was constructed. Patients in high-risk group had a significantly worse prognosis than that of low-risk (P<0.0001). Immune infiltration analysis found that patients identified as high-risk had a higher infiltration of macrophages and tumor-associated fibroblasts. Further pathway analysis revealed that the signature may be involved in epithelial mesenchymal transition, extracellular matrix receptor interaction, and focal adhesion. Finally, a competitive endogenous inhibition relationship was discovered between LINC01094, KRT7-AS, MYCNOS, ZNF32-AS2, AC012236.1 and pyroptosis- related genes such as IRF1, NOD1, GSDMC, NLRP1, PLCG1, GSDME and GZMB, in which LINC01094 and KRT7-AS were found to be overexpressed in three ovarian cancer cell lines. Conclusion: We constructed a pyroptosis-related lncRNA signature and correlate it to the immune microenvironment. A ceRNA regulatory network related to pyroptosis was also constructed, which provides novel insights useful for the study of pyroptosis in ovarian cancer.


Capillary basement membrane changes in adolescents with type 1 diabetes.
Measurements were made of muscle capillary basement membrane thickness (CBMT) in 95 normal boys and girls and 167 postpubescent insulin-dependent diabetics. Of 110 diabetics in whom "higher" degrees of metabolic control were maintained, only two had increased CBMT values. Of 57 diabetics in whom "lower" degrees of metabolic control were maintained, 26 had increased CBMT values. Two or more muscle biopsies were done in each of 65 diabetic subjects: Mean CBMT values of 24 subjects with "higher" degrees of metabolic control for two to nine years remained within the normal range; values of 23 subjects with "lower" degrees of metabolic control for only one to three years increased from 858 +/- 142 A to 1,155 +/- 227 A: values of 13 subjects who had been in "lower" degrees of control decreased from 1,255 +/- 232 A to 869 +/- 135 A after maintaining "improved" metabolic control for about a year. In postpubescent diabetics, the CBMT is labile and progresses or regresses depending on the degree of metabolic control.


Characteristics and enhanced antioxidant activity of egg white protein selenized by dry-heating in the presence of selenite.
This study reports a new method for the selenization of food proteins. Egg white protein (EWP) was selenized by dry-heating in the presence of selenite, and the physiochemical and functional properties of the selenized EWP were investigated. Selenization was accelerated with a decrease in pH from 7.0 to 3.0, an increase in heating time from 1 to 5 days, and an increase in incubation temperatures from 25 to 80 °C. The electrophoretic mobility of EWP increased with an increase in the level of selenization. Heat-induced polymerization of EWP was promoted by dry-heating in the presence of selenite. The selenite group was acid-stable and base-labile, which suggests that it was bound to the hydroxyl group of an amino acid and formed an -O-SeHO2 linkage. (77)Se NMR spectral data also suggested that the selenite bond (-O-SeHO2) was bound to EWP. The digestibility of EWP was improved by selenization. The antioxidant activities of EWP, including ABTS(+) free radical scavenging capacity, hydroxyl radical scavenging capacity, reducing power, and the Fe(2+) chelating capacity, were remarkably enhanced by selenization. This finding is the first to describe that EWP can be selenized by dry-heating in the presence of selenite and that the antioxidant activities of EWP are markedly enhanced by selenization. This points to a potentially new method for generating antioxidant food protein and a new method for preparing organic Se.


[How is bone formed and resorbed?-- molecular mechanisms of bone formation and resorption].
Bone has developed as a storage of calcium as well as a supporting tissue in vertebrates. Bone is a complex tissue in which resorption and formation take place throughout life. This process is called bone remodeling. Osteotrophic hormones such as 1 alpha,25-dihydroxyvitamin D3[1 alpha,25 (OH) 2D3], parathyroid hormone (PTH) and calcitonin maintain serum calcium homeostasis within a narrow range of 9 to 10 mg/dl by regulating intestinal absorption of calcium and bone remodeling. Bone tissue contains various types of cells, of which bone-forming osteoblasts and bone-resorbing osteoclasts are mainly responsible for bone remodeling. Osteoblasts arise from common progenitors with chondrocytes, myotubes and adipocytes. Recently, four research groups independently identified core-binding protein alpha-1(Cbfa-1) as a key transcription factor for osteoblast differentiation and bone formation, since Cbaf-1 knockout mice completely lacked bone formation due to maturation arrest of osteoblasts. In contrast, multinucleated osteoclasts are primarily responsible for bone resorption. The recent discovery of new members of tumor necroses factor (TNF) receptor-ligand family has indicated the precise mechanism by which osteoblasts/stromal cells regulate osteoclast formation. Osteoblasts/stromal cells express a new member of the TNF ligand family "osteoclast differentiation factor (ODF)" as a membrane-associated factor. Osteoclast progenitors which express ODF receptor(RANK) recognize ODF through cell-to-cell interaction with osteoblasts/stromal cells, then differentiate into osteoclats. Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble decoy receptor for ODF. Thus, ODF, RANK and OPG/OCIF are the three key molecules for osteoclast formation. The discovery of Cbfa-1 and ODF may establish a new way to treat several metabolic bone diseases caused by abnormal bone formation and resorption.


Peritubal adhesions in infertile women: diagnosis with hysterosalpingography.
We studied the efficacy of hysterosalpingography in the detection of peritubal adhesions without tubal occlusion by using laparoscopy as the gold standard for the diagnosis. Peritubal adhesions were diagnosed on hysterosalpingography by using the following radiographic criteria alone or in combination: (1) convoluted fallopian tube, (2) loculation of spillage of contrast medium into the peritoneal cavity, (3) ampullary dilatation, (4) peritubal halo effect (double-contour appearance of the tubal wall), and (5) vertical fallopian tube. The first 100 patients with the diagnosis of adhesions on hysterosalpingography who also had laparoscopy were included in the study. Seventy-five patients had the diagnosis confirmed on laparoscopy, resulting in a 25% false-positive diagnosis of adhesions with hysterosalpingography. Thirty-nine (52%) of these 75 patients had one radiographic finding alone, and 20 of these patients had loculation of spillage of contrast medium. Although the patients with adhesions tended to have two or more of the radiographic findings, the difference was not statistically significant. The most frequent radiographic findings found in combination were convoluted fallopian tube and loculation of spillage of contrast medium. These findings suggest that hysterosalpingography can be the diagnostic procedure of choice in the initial investigation of infertility due to peritubal adhesions.


Exposure to lead and length of time needed to make homes lead-safe for young children.
We determined the length of time needed to make homes lead-safe in a population of children aged 0 to 6 years with blood lead levels (BLLs) of 20 micrograms per deciliter (mug/dL) or greater. Reducing this time would reduce children's exposure to lead. Data came from the Wisconsin Childhood Lead Poisoning Prevention Program's comprehensive blood lead surveillance system. Analysis was restricted to children whose first BLL test value during 1996-1999 was between 20 and 40 mug/dL and for whom housing intervention data were available (n=382). The median length of time required to make a home lead-safe was 465 days. Only 18% of children lived in homes that were made lead-safe within 6 months; 45% lived in homes requiring more than 18 months to be lead-safe. Efforts are needed to reduce the time it takes to make a home lead-safe. Although abatement orders always include time limits, improved compliance with the orders must be enforced. Greater emphasis should be placed on securing lead-safe or lead-free housing for families, thus reducing lead exposure.


The role of the thyroid in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.


SEXUAL SELECTION IN A WOLF SPIDER: MALE DRUMMING ACTIVITY, BODY SIZE, AND VIABILITY.
Females are often believed to actively choose highly ornamented males (males with extravagant morphological signals or intense sexual display), and ornaments should be honest signals of male viability. However, this belief is relying only on some pieces of empirical evidence from birds. Our study reports active female choice on sexual display that indicates male viability in spiders. We established trials in which we studied female choice in relation to male courtship drumming activity and body size. Females chose the most actively drumming males as mating partners, but the body size of the males did not seem to be selected. Male drumming activity turned out to be a good predictor of male viability, whereas male viability was independent of male body mass. Our results suggest that by actively choosing mates according to male drumming performance, but independently of male body mass, females are preferring viable males as mates. Because Hygrolycosa rubrofasciata males do not provide obvious direct benefits to their offspring, females may gain some indirect benefits; offspring may have higher chance of survival, or the offspring may inherit the attractiveness of their father.


Peptide hydrophobicity controls the activity and selectivity of magainin 2 amide in interaction with membranes.
The magainins are antibacterial peptides from the skin of Xenopus laevis. They show a broad range of activity against prokaryotic cells but lyse eukaryotic cells poorly. To elucidate the influence of peptide hydrophobicity on membrane activity and selectivity, we designed and synthesized analogs of magainin 2 amide with slightly varying hydrophobicities but retained hydrophobic moment, peptide charge, and angle subtended by the hydrophilic helix region. Circular dichroism investigations of the peptides revealed that all peptides investigated adopt an alpha-helical conformation when bound to phospholipid vesicles. Dye-releasing experiments from vesicles of phosphatidylglycerol (PG) showed that the membrane-permeabilizing activity of the analogs is not influenced by peptide hydrophobicity. In contrast, the permeability-enhancing activity on vesicles bearing high amounts of phosphatidylcholine (PC) increases drastically with enhanced peptide hydrophobicity, resulting in a reduced selectivity of more hydrophobic analogs for negatively charged membranes. Likewise, the peptide affinity to PC-rich membranes increases in the order of hydrophobicity. Correlation of peptide binding and membrane permeabilization of PC/PG (3:1) vesicles revealed that the observed differences in peptide activity on membranes of low negative surface charge are mainly caused by the different binding affinities. The antibacterial and hemolytic activity of the peptides increases with enhanced hydrophobicity. A strong correlation was found between the hemolytic effect and the bilayer-permeabilizing activity against PC-rich vesicles. Whereas the antibacterial specificity of the more hydrophobic analogs is retained for Escherichia coli, the specificity for Pseudomonas aeruginosa decreases with increasing hydrophobicity.


Unstable thoracolumbar fractures. A study by CT and conventional roentgenology of the reduction effect of Harrington instrumentation.
Fourteen patients with unstable thoracolumbar fractures were examined with conventional roentgenologic technique and CT before and after operation with Harrington instrumentation. CT was superior in evaluating posterior elements, bone fragments in the spinal canal, and degree of narrowing of the spinal canal. Harrington rods restored the general spinal alignment. However, even after surgery, the midsagittal diameter, as well as the cross-sectional area of the spinal canal were still diminished by 26%. The reduction of the spinal canal improved significantly by early surgical intervention. Open reduction and stabilization with Harrington rods and fusion within three days after injury is recommended.


"PEAR-ing" Genomic and Epigenomic Analyses for Cancer Gene Discovery.
Somatic structural variants in tumor genomes can deregulate transcription through repositioning of enhancer elements. A new method, PEAR-ChIP, leverages paired-end H3K27ac chromatin immunoprecipitation combined with high-throughput sequencing and current computational methods to identify such events.


[A survey of sexual psychology and attitude of Chinese peace-keepers in Liberia].
To investigate the sexual psychology and sexual attitude of the Chinese peace-keepers in Liberia, attempting a correct guidance and psychological intervention in this aspect. In the middle of the mission tour, a survey was conducted among 314 Chinese male peace-keeping soldiers with a self-designed questionnaire. More than 90% of the soldiers learned some sexual knowledge by themselves; quite a proportion of them were relatively deficient in sexual knowledge and lacked sexual education; 77% of them were afraid of AIDS even after sexual education. Married soldiers showed more maturity in sexual psychology than Appropriate psychological intervention the unmarried(P <0.05) , but with no differences in sexual attitude( P >0. 05). and guidance directed at the particulate population of peace-keepers may help them adopt a rational attitude towards their sexual drive and desire and convert, their sexual energy into further impetus to better creative performance in the peace-keeping mission.


The production and characterisation of monoclonal antibodies to myc, c-erbB-2 and EFG-receptor using a synthetic peptide approach.
Monoclonal antibodies to myc, c-erbB-2 and epidermal growth factor-receptor (EGF-R) were raised using a synthetic peptide approach. The antibodies were characterised by ELISA, immunoblotting, immunoprecipitation and immunocytochemical procedures against cognate peptide and native proteins. All of the monoclonal antibodies detected peptide-blockable bands of appropriate molecular weight (myc-p62/66 kDa, c-erbB-2-185kDa; EGF-R-150/170 kDa) on immunoblots. The monoclonal antibodies to c-erbB-2 and EGF-R immunostained subpopulations of tumour cells on sections of formalin-fixed, paraffin wax embedded human infiltrating and invasive ductal carcinomas of breast. Intense blood cell staining was observed with the EGF-R antibody. This staining was shown to be peptide blockable and may reveal a true localisation for the EGF-receptor protein, a closely-related (erbB) protein or a degradation product. The monoclonal antibody to a common peptide from the myc protein family was epitope scanned using a modification of the Geysen pin technique. Hexapeptide sequence Ala-Pro-Ser-Glu-Asp-Ile was found to be bound most strongly by the myc monoclonal antibody, and amino acids Pro2 and Glu4 were found to be essential for antibody binding. The use of synthetic peptides for the production of monoclonal antibodies with predetermined specificity, which may be precisely identified using the epitope scanning technique, is discussed.


An unusual cause of dyspnea in a patient with relapsing breast cancer.
Bilateral diaphragmatic paralysis (BDP) is usually caused by anatomic lesions of both phrenic nerves or generalized neurologic diseases. BDP has also been observed during and after infections, associated with mediastinal tumors, or may have an idiopathic etiology. A 57-year-old woman with breast cancer had progressive dyspnea that worsened when in the supine position. Lung function tests and phrenic nerve stimulation revealed bilateral diaphragmatic paralysis. Clinical suspicion of BDP should always be raised in patients suffering from progressive dyspnea and orthopnea. Determination of (VC) when standing and in the supine position and measurement of trandiaphragmatic pressure should reveal this uncommon diagnosis.


Schizophrenia: more evidence for less glutamate.
Evaluation of: Hahn CJ, Hoau-Yan W, Dan-Sung C et al. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med. 12, 824-828 (2006). Schizophrenia may be associated with deficits in glutamate transmission at the N-methyl-D-aspartate (NMDA) receptor complex. Recent work has shown that neuregulin 1 (NRG1) acts via ErbB4 receptors to inhibit NMDA receptor currents. This is important given that NRG1 is a convincing susceptibility gene in schizophrenia. Hahn and colleagues add to our knowledge of NRG1 modulation of NMDA receptors and show intriguing differences between control and schizophrenic brains. NMDA receptors in the schizophrenic prefrontal cortex showed smaller responses to exogenously applied NMDA/glycine. Furthermore, NMDA receptors in tissue from schizophrenic patients appeared to be more sensitive to the inhibitory effects of a fixed dose of NRG1. In agreement, the ErbB4-PSD-95-NMDA complex was more tightly coupled in schizophrenic brains and NRG1-mediated stimulation of ErbB4 was markedly enhanced. These findings underscore the importance of NMDA receptors in schizophrenia and support therapeutic strategies aimed at boosting glutamate transmission.


Endoplasmic reticulum-retention C-terminal sequence enhances production of an 11S seed globulin from Amaranthus hypochondriacus in Pichia pastoris.
The methylotrophic yeast Pichia pastoris was used to express an 11S seed globulin from Amaranthus hypochondriacus. Three different plasmids were tested for expression of amarantin. One of them, which included the untranslated regions (UTR) of the full cDNA, failed to express the amarantin under tested conditions, whereas the other plasmids, one without UTR and the other similar but including the endoplasmic reticulum-retention signal KDEL, were able to express the proamarantin in P. pastoris. After 48 h of induction, KDEL-proamarantin had accumulated quite significantly compared to unmodified proamarantin. Different solubilization patterns were also obtained from both proamarantin versions; only soluble protein was obtained from the system that included the KDEL retrieval signal. Protein fractionation was carried out by differential precipitation with ammonium sulfate, and proamarantin purification was performed using an HPLC ion exchange column. The endoplasmic reticulum-retention C-terminal sequence (KDEL retrieval signal), not commonly employed in this heterologous expression system, can therefore be used to enhance accumulation of recalcitrant protein in P. pastoris. The results obtained here also suggest that this expression system is suitable for expression and evaluation of engineered seed globulin proteins.


The water intensity of the plugged-in automotive economy.
Converting light-duty vehicles from full gasoline power to electric power, by using either hybrid electric vehicles or fully electric power vehicles, is likely to increase demand for water resources. In the United States in 2005, drivers of 234 million cars, lighttrucks, and SUVs drove approximately 2.7 trillion miles and consumed over 380 million gallons of gasoline per day. We compare figures from literature and government surveys to calculate the water usage, consumption, and withdrawal, in the United States during petroleum refining and electricity generation. In displacing gasoline miles with electric miles, approximately 2-3 [corrected] times more water is consumed (0.24 [corrected] versus 0.07--0.14 gallons/mile) and over 12 [corrected] times more water is withdrawn (7.8 [corrected] versus 0.6 gallons/mile) primarily due to increased water cooling of thermoelectric power plants to accommodate increased electricity generation. Overall, we conclude that the impact on water resources from a widespread shift to grid-based transportation would be substantial enough to warrant consideration for relevant public policy decision-making. That is not to say that the negative impacts on water resources make such a shift undesirable, but rather this increase in water usage presents a significant potential impact on regional water resources and should be considered when planning for a plugged-in automotive economy.


The problem of unstable angina pectoris: myocardial infarction register data from Kaunas, Lithuanian SSR.
Prodromal symptoms and signs of acute myocardial infarction (AMI) and clinical course of unstable angina pectoris were studied in 405 patients with AMI and 165 patients with unstable angina, respectively. The latter group consisted of patients admitted to a coronary care department. The study showed that 81.2% of patients with AMI had had a number of symptoms during the 28-day period preceding the onset of AMI. Neither the patients nor the physicians had given proper and timely attention to them. The hospitalization of patients with unstable angina was, in some cases, effective in preventing development of AMI or in eliminating life-threatening complications of AMI. This resulted in a decline of the AMI mortality.


Low Temperature Chemoresistive Oxygen Sensors Based on Titanium-Containing Ti2CTx and Ti3C2Tx MXenes.
The chemoresistive properties of multilayer titanium-containing Ti2CTx and Ti3C2Tx MXenes, synthesized by etching the corresponding MAX phases with NaF solution in hydrochloric acid, and the composites based on them, obtained by partial oxidation directly in a sensor cell in an air flow at 150 °C, were studied. Significant differences were observed for the initial MXenes, both in microstructure and in the composition of surface functional groups, as well as in gas sensitivity. For single Ti2CTx and Ti3C2Tx MXenes, significant responses to oxygen and ammonia were observed. For their partial oxidation at a moderate temperature of 150 °C, a high humidity sensitivity (T, RH = 55%) is observed for Ti2CTx and a high and selective response to oxygen for Ti3C2Tx at 125 °C (RH = 0%). Overall, these titanium-containing MXenes and composites based on them are considered promising as receptor materials for low temperature oxygen sensors.


A study of deliberate self-poisoning in patients with adjustment disorders.
A sample of 140 patients (34 men and 106 women), hospitalized for deliberate self-poisoning in a toxicological clinic, was evaluated clinically and by Pöldinger's risk list for assessment of suicidality. All subjects met the criteria of DSM-IV adjustment disorder with no additional Axis I and Axis II comorbidity. 18% of the patients had a chronic adjustment disorder. The most common problems on Axis IV were those with the primary support group (especially in women). Occupational and economic problems were more frequent in men than in women. Most of the studied subjects undertook the suicidal attempt impulsively. Suicidal thoughts after deliberate self-poisoning persist in only 11% of the patients. The suicidal risk measured by Pöldinger's risk list for assessment of suicidality was negligible in 4/5 of the cases. The suicidal risk was higher in patients with chronic adjustment disorder and in patients with previous suicide attempts. The most represented age group - from 15 to 19 years old showed the highest suicidal risk. In women the suicidal risk increased with age. Women with impulsive suicide attempt showed a lower suicidal risk than women with a non-impulsive suicide attempt. A cathartic and abreactive effect of the suicide attempt was detected, but this effect only partially accounts for the relatively low percentage of suicidal thoughts after the suicidal act and the insignificant suicidal risk in 4/5 of the studied subjects.


High phylogenetic diversity of Gallibacterium anatis is correlated with low biosecurity measures and management practices on poultry farms.
Gallibacterium anatis is considered one of the most common bacterial causative agents of reproductive tract disorders in poultry. In this study, phylogenetic analysis of partial rpoB sequences and biotyping using MALDI-TOF MS was done in order to investigate the genetic diversity of Gallibacterium isolates from 13 farms with different biosecurity measures and management practices. Sampling was done as a part of regular monitoring, except for Farms 9-13 that were included in the study to represent extensive production systems with lowest biosecurity levels. Pharyngeal and cloacal swabs were taken from live birds, while swabs from trachea, liver, peritoneum and oviduct were taken during necropsies. After cultivation and identification, strains from each farm were randomly selected for sequencing and biotyping. Both results showed high level of heterogeneity among the isolates originating from farms with low biosecurity levels, unlike isolates from farms with higher biosecurity levels and proper management that were more closely related and clustered together. Such correlation was statistically significant. Low biosecurity levels enable horizontal transmission of the pathogens, as well as gene transfer. The results confirm the importance of adequate biosecurity measures and management on poultry farms as they greatly affect the genetic diversity of the pathogens. Therefore, implementation of basic biosecurity measures could help control the heterogeneity of Gallibacterium strains, which would alleviate control of the infection prevalence on farms through immunoprophylaxis, and consequently improve poultry production. Also, the genetic diversity of G. anatis on poultry farms could be a good bioindicator of management practices and biosecurity measures used. RESEARCH HIGHLIGHTS High correlation between low biosecurity and high diversity of Gallibacterium anatis. Diversity of Gallibacterium is a good bioindicator of management practices on farms.


Otologic manifestations of experimental rhinovirus infection.
Episodes of acute otitis media are commonly associated with viral upper respiratory tract infections. Rhinoviruses account for approximately 40% of these infections, and were previously shown to alter eustachian tube function and middle ear pressures. However, progression to otitis media has not been prospectively documented. In the present study, changes in tympanometric pressures and otoscopic findings resulting from experimental intranasal rhinovirus type-39 inoculation were documented in 60 adult volunteers. Fifty-seven (95%) subjects became infected and 34 (60%) of these had a clinical cold. Prior to viral inoculation, 3 (5%) subjects had middle ear pressures of less than -100 mm H2O and two of these subjects developed middle ear effusions following infection. In all, 22 (39%) subjects developed middle ear pressures of less than -100 mm H2O. No subject with normal middle ear pressures prior to infection developed evidence of effusion. This study extends the otologic manifestations of rhinovirus infection to include otitis media. Furthermore, these results support the hypothesized relationship between upper respiratory tract infections, eustachian tube dysfunction, and otitis media.


Publicity as policy: the changing role of press and public relations at the BMA, 1940s-80s.
Relationships between policy and publicity or public relations (PR) have been questioned since the emergence of professional public relations in the early-twentieth century. In the field of health and medicine organised PR activity began to flourish in the decades following World War Two. Its presence became evident in government departments, in professional associations, voluntary bodies and campaigning groups. Increasingly, policy decisions had to be publicly performed through rituals like the press conference. This chapter documents the development of press and PR activity at the British Medical Association (BMA) from the 1950s to the 1980s. The BMA provides a well-documented case, which can be used to suggest broader shifts in the association between policy and publicity.


The origin of replicators and reproducers.
Replicators are fundamental to the origin of life and evolvability. Their survival depends on the accuracy of replication and the efficiency of growth relative to spontaneous decay. Infrabiological systems are built of two coupled autocatalytic systems, in contrast to minimal living systems that must comprise at least a metabolic subsystem, a hereditary subsystem and a boundary, serving respective functions. Some scenarios prefer to unite all these functions into one primordial system, as illustrated in the lipid world scenario, which is considered as a didactic example in detail. Experimentally produced chemical replicators grow parabolically owing to product inhibition. A selection consequence is survival of everybody. The chromatographized replicator model predicts that such replicators spreading on surfaces can be selected for higher replication rate because double strands are washed away slower than single strands from the surface. Analysis of real ribozymes suggests that the error threshold of replication is less severe by about one order of magnitude than thought previously. Surface-bound dynamics is predicted to play a crucial role also for exponential replicators: unlinked genes belonging to the same genome do not displace each other by competition, and efficient and accurate replicases can spread. The most efficient form of such useful population structure is encapsulation by reproducing vesicles. The stochastic corrector model shows how such a bag of genes can survive, and what the role of chromosome formation and intragenic recombination could be. Prebiotic and early evolution cannot be understood without the models of dynamics.


Disentangling Component Dynamics in an All-Polymer Nanocomposite Based on Single-Chain Nanoparticles by Quasielastic Neutron Scattering.
We have investigated an all-polymer nanocomposite (NC) consisting of single-chain nanoparticles (SCNPs) immersed in a matrix of linear chains of their precursors (25/75% composition in weight). The SCNPs were previously synthesized via "click" chemistry, which induces intramolecular cross-links in the individual macromolecules accompanied by a slight shift (5-8 K) of the glass transition temperature toward higher values and a broadening of the dynamic response with respect to the raw precursor material. The selective investigation of the dynamics of the NC components has been possible by using properly isotopically labeled materials and applying quasielastic neutron scattering techniques. Results have been analyzed in the momentum transfer range where the coherent scattering contribution is minimal, as determined by complementary neutron diffraction experiments with polarization analysis. We observe the development of dynamic heterogeneity in the intermediate scattering function of the NC components, which grows with increasing time. Local motions in the precursor matrix of the NC are accelerated with respect to the reference bulk behavior, while the displacements of SCNPs' hydrogens show enhanced deviations from Gaussian and exponential behavior compared with the pure melt of SCNPs. The resulting averaged behavior in the NC coincides with that of the pure precursor, in accordance with the macroscopic observations by differential scanning calorimetry (DSC) experiments.


[Chronic Compartment Syndrome].
Chronic compartment syndromes are a rare, but frequently overlooked cause of pain in the locomotor system. Their aetiology is still not fully elucidated. There is an imbalance of muscle volume and space in the compartment. Thickening of the fascia and decreased elasticity lead to a pathological increase in pressure in the compartment under load. Chronic compartment syndromes are found in the foot, lower leg, thigh, forearm, hand, and even the spine. Bilateral compartment syndromes are very common (80 %). The main symptoms are pain in the compartment under physical activity. Compartment pressure measurement is the gold standard examination. Other diagnostic procedures are near-infrared spectroscopy, MRI and ultrasound. As conse rvative treatment often fails, surgical treatment becomes necessary. Different techniques are described in the literature. We prefer an endoscopy-assisted minimally-invasive approach.


Chiral Metal-Organic Frameworks.
In the past two decades, metal-organic frameworks (MOFs) or porous coordination polymers (PCPs) assembled from metal ions or clusters and organic linkers via metal-ligand coordination bonds have captivated significant scientific interest on account of their high crystallinity, exceptional porosity, and tunable pore size, high modularity, and diverse functionality. The opportunity to achieve functional porous materials by design with promising properties, unattainable for solid-state materials in general, distinguishes MOFs from other classes of materials, in particular, traditional porous materials such as activated carbon, silica, and zeolites, thereby leading to complementary properties. Scientists have conducted intense research in the production of chiral MOF (CMOF) materials for specific applications including but not limited to chiral recognition, separation, and catalysis since the discovery of the first functional CMOF (i.e., d- or l-POST-1). At present, CMOFs have become interdisciplinary between chirality chemistry, coordination chemistry, and material chemistry, which involve in many subjects including chemistry, physics, optics, medicine, pharmacology, biology, crystal engineering, environmental science, etc. In this review, we will systematically summarize the recent progress of CMOFs regarding design strategies, synthetic approaches, and cutting-edge applications. In particular, we will highlight the successful implementation of CMOFs in asymmetric catalysis, enantioselective separation, enantioselective recognition, and sensing. We envision that this review will provide readers a good understanding of CMOF chemistry and, more importantly, facilitate research endeavors for the rational design of multifunctional CMOFs and their industrial implementation.


Review article: late post-hysterectomy ectopic pregnancy.
Ectopic pregnancy after hysterectomy is a rare but potentially life-threatening condition requiring prompt diagnosis to prevent the increased mortality associated with rupture. Twenty-seven cases of late post-hysterectomy ectopic pregnancy reported in the English literature since 1918 were reviewed and analysed for presenting symptoms, missed diagnosis rate at initial presentation, location of ectopic and rupture rate at diagnosis. The presenting symptoms were found to be non-specific. The diagnosis in this population is twice more likely to be missed than in women with intact uteri. The rupture rate is 63%, compared with 37% in women with intact uteri. The majority of late post-hysterectomy ectopic pregnancies (62%) were located in the fallopian tubes. Because of the potential risk of mortality, emergency physicians should always consider the possibility of ectopic pregnancy in childbearing women whose surgical history includes hysterectomy without oophorectomy. Evaluation of abdominal pain in this population should include a pregnancy test to ensure prompt diagnosis when the possibility of pregnancy exists clinically.


Slow Activity in Focal Epilepsy During Sleep and Wakefulness.
We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG recording. We studied the EEG power spectral density during wakefulness and sleep in delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-20 Hz) bands. During sleep, patients with focal epilepsy showed higher power from delta to beta frequency bands compared with controls. The effect was widespread for alpha band and above, while localized over the affected hemisphere for delta (sleep cycle 1, P = .006; sleep cycle 2, P = .008; sleep cycle 3, P = .017). The analysis of interhemispheric differences showed that the only frequency band stronger over the affected regions was the delta band during the first 2 sleep cycles (sleep cycle 1, P = .014; sleep cycle 2, P = .002). During wakefulness, patients showed higher delta/theta activity over the affected regions compared with controls. Patients with focal epilepsy showed a pattern of power increases characterized by a selective slow wave activity enhancement over the epileptic regions during daytime and sleep. This phenomenon was stronger and asymmetric during the first sleep cycles.


Bisecting real and fake body parts: effects of prism adaptation after right brain damage.
The representation of body parts holds a special status in the brain, due to their prototypical shape and the contribution of multisensory (visual and somatosensory-proprioceptive) information. In a previous study (Sposito et al., 2010), we showed that patients with left unilateral spatial neglect exhibit a rightward bias in setting the midpoint of their left forearm, which becomes larger when bisecting a cylindrical object comparable in size. This body part advantage, found also in control participants, suggests partly different processes for computing the extent of body parts and objects. In this study we tested 16 right-brain-damaged patients, and 10 unimpaired participants, on a manual bisection task of their own (real) left forearm, or a size-matched fake forearm. We then explored the effects of adaptation to rightward displacing prism exposure, which brings about leftward aftereffects. We found that all participants showed prism adaptation (PA) and aftereffects, with right-brain-damaged patients exhibiting a reduction of the rightward bias for both real and fake forearm, with no overall differences between them. Second, correlation analyses highlighted the role of visual and proprioceptive information for the metrics of body parts. Third, single-patient analyses showed dissociations between real and fake forearm bisections, and the effects of PA, as well as a more frequent impairment with fake body parts. In sum, the rightward bias shown by right-brain-damaged patients in bisecting body parts is reduced by prism exposure, as other components of the neglect syndrome; discrete spatial representations for real and fake body parts, for which visual and proprioceptive codes play different roles, are likely to exist. Multisensory information seems to render self bodily segments more resistant to the disruption brought about by right-hemisphere injury.


Iatrogenic Preterm Premature Rupture of Membranes after Fetoscopic Laser Ablative Surgery.
To describe the incidence and risk factors for iatrogenic premature preterm rupture of membranes (iPPROM) after fetoscopic laser surgery for the twin-to-twin-transfusion syndrome. This is a retrospective review of all patients who have undergone fetoscopic laser surgery at a single fetal treatment center since 2000. We defined iPPROM as spontaneous rupture of membranes before the onset of labor prior to 34 weeks of gestation. The iPPROM cohort was compared to the cohort without iPPROM for several preoperative, operative, and delivery characteristics. Ninety-two consecutive patients were reviewed. The overall rate of iPPROM was 18.5% (n = 17). The rates of iPPROM within 1 and 4 weeks were 5.4 and 10.9%, respectively. The median interval from surgery to delivery was significantly shorter in the iPPROM group (21 vs. 62 days, p = 0.01). The mean gestational age at delivery (27.0 vs. 31.1 weeks, p = 0.02) was lower in the iPPROM group. No other characteristics studied differed significantly between the groups. The incidence of iPPROM was substantially lower than in recent multicenter reports; however, no risk factors of iPPROM could be identified. Whether this is related to variations in surgical or anesthetic management will require further investigation.


Protocol for hepatitis screening and follow-up of Southeast Asian refugees.
Hepatitis B virus (HBV) infection is prevalent among Southeast Asian refugees. HBV infection causes acute and chronic hepatitis and cirrhosis, and is associated with primary hepatocellular carcinoma. Health care providers must be able to make an accurate diagnosis of acute or chronic HBV infection when performing medical evaluations of Southeast Asian refugees. It is essential that appropriate follow-up care and teaching regarding infection control be provided. In this article, a protocol is presented that aids interpretation of hepatitis B screening tests. The protocol uses testing for the immunoglobulin M antibody against hepatitis B core antigen (anti-HBc/IgM) to aid differentiation between acute and chronic HBV infection. If testing is interpreted to show the presence of the hepatitis B chronic carrier state, a second protocol is used to guide follow-up testing, treatment and referral of patients.


[The fatty acid composition of total lipids and triglycerides in several actinomycetes].
Saturated and unsaturated fatty acids (C13-C18) have been found in the composition of lipids and triglycerides of actinomycetes by GLC. Qualitative composition of fatty acids was identical on chemically defined and organic media. Synthesis of unsaturated fatty acids by the actinomycetes was intensive (total yield over 50% and even 84.2% in Act. canosus) on the organic medium I which may be recommended for production of lipid fractions with elevated content of unsaturated fatty acids.


Araliasaponin II isolated from leaves of Acanthopanax henryi (Oliv.) Harms inhibits inflammation by modulating the expression of inflammatory markers in murine macrophages.
Araliasaponin II (AS II) is a bioactive compound isolated from Acanthopanax henryi (Oliv.) Harms, a plant widely used in traditional oriental medicine. The present study investigated the anti‑inflammatory effects of AS II using murine macrophages. The effects of AS II on inflammatory mediator and cytokine production in lipopolysaccharide (LPS)‑stimulated RAW 264.7 cells was evaluated. Nitric oxide (NO) and cytokine production were determined using the Griess reagent and an ELISA kit. The expression levels of cytokines, inducible NO synthase (iNOS) and cyclooxygenase‑2 (COX‑2) mRNA were examined by reverse transcription‑quantitative polymerase chain reaction. The expression levels of iNOS, COX‑2 and toll‑like receptor (TLR)‑4 protein were examined by western blotting. Translocation of nuclear factor‑κB (NF‑κB) and TLR‑4 expression were visualized by immunofluorescence staining. AS II markedly inhibited the production of NO and prostaglandin E2, and reduced iNOS and COX‑2 expression at the transcriptional and translational levels. AS II downregulated the expression of interleukin‑6 and tumor necrosis factor‑α at the protein and mRNA levels. Furthermore, pre‑treatment with AS II significantly suppressed the TLR‑4‑NF‑κB signaling pathway; this effect may be cause by AS II competing with LPS for binding to TLR‑4 and subsequently inhibiting translocation of the NF‑κB/p65 protein to the nucleus. The results suggested that the anti‑inflammatory properties of AS II may result from inhibiting pro‑inflammatory mediators by suppressing the initiation of the inflammatory response and inhibiting TLR-4-NF-κB signaling pathways.


The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2.
A series of halogenated derivatives of natural flavonoids: baicalein and chrysin were designed and investigated as possible ligands for the catalytic subunit of tumor-associated human kinase CK2. Thermal shift assay method, in silico modeling, and high-performance liquid chromatography-derived hydrophobicity together with IC50 values determined in biochemical assay were used to explain the ligand affinity to the catalytic subunit of human protein kinase CK2. Obtained results revealed that substitution of baicalein and chrysin with halogen atom increases their binding affinity to hCK2α, and for 8-chlorochrysin the observed effect is even stronger than for the reference CK2 inhibitor-4,5,6,7-tetrabromo-1H-benzotriazole. The cytotoxic activities of the baicalein and chrysin derivatives in the in vitro model have been evaluated for MV4-11 (human biphenotypic B myelomonocytic leukemia), A549 (human lung adenocarcinoma), LoVo (human colon cancer), and MCF-7 (human breast cancer) as well as on the nontumorigenic human breast epithelial MCF-10A cell lines. Among the baicalein derivatives, the strongest cytotoxic effect was observed for 8-bromobaicalein, which exhibited the highest activity against breast cancer cell line MCF-7 (IC50 10 ± 3 μM). In the chrysin series, the strongest cytotoxic effect was observed for unsubstituted chrysin, which exhibited the highest activity against leukemic cell line MV4-11 (IC50 10 ± 4 μM).


Rank-ordered multifractal analysis for intermittent fluctuations with global crossover behavior.
The rank-ordered multifractal analysis (ROMA), a recently developed technique that combines the ideas of parametric rank ordering and one-parameter scaling of monofractals, has the capabilities of deciphering the multifractal characteristics of intermittent fluctuations. The method allows one to understand the multifractal properties through rank-ordered scaling or nonscaling parametric variables. The idea of the ROMA technique is applied to analyze the multifractal characteristics of the auroral zone electric-field fluctuations observed by the SIERRA sounding rocket. The observed fluctuations span across contiguous multiple regimes of scales with different multifractal characteristics. We extend the ROMA technique such that it can take into account the crossover behavior--with the possibility of collapsing probability distribution functions--over these contiguous regimes.


Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases.
Neurodegenerative diseases are a common cause of morbidity and cognitive impairment in older adults. Most clinicians who care for the elderly are not trained to diagnose these conditions, perhaps other than typical Alzheimer's disease (AD). Each of these disorders has varied epidemiology, clinical symptomatology, laboratory and neuroimaging features, neuropathology, and management. Thus, it is important that clinicians be able to differentiate and diagnose these conditions accurately. This review summarizes and highlights clinical aspects of several of the most commonly encountered neurodegenerative diseases, including AD, frontotemporal dementia (FTD) and its variants, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and Huntington's disease (HD). For each condition, we provide a brief overview of the epidemiology, defining clinical symptoms and diagnostic criteria, relevant imaging and laboratory features, genetics, pathology, treatments, and differential diagnosis.


Cholesterol metabolism in the laying hen as influenced by dietary cholesterol, caloric intake, and genotype.
Three trials, each with 24 hens, were conducted to determine the effects of dietary cholesterol, caloric intake, and genotype on the synthesis, storage, and excretion of cholesterol in the laying hen. The two genotypes of birds used in this experiment had been divergently selected for high and low oxygen consumption and had been shown to differ significantly (P less than .01) in body weight gain and carcass lipid deposition from 0 to 4 weeks of age. The dietary treatment, administered for a 2-week period to birds in each genotype, consisted of two levels of dietary cholesterol (0 and 1% added) and two energy intakes (ad libitum and 75% ad libitum). The experimental design was a 2 X 2 X 2 factorial. One percent added cholesterol versus none supplemented produced a significant (P less than .01) decrease in available metabolizable energy and uptake of acetate into liver cholesterol while causing significant (P less than .01) increases in egg and liver cholesterol but not in plasma cholesterol. Restricting caloric intake, as compared to ad libitum feeding, resulted in significantly (P less than .01) decreased egg production and total amount of cholesterol excreted via the egg with significantly (P less than .05) increased plasma and liver cholesterol levels but no change in egg cholesterol concentration. Differences were significant (P less than .05) between the two genotypes in feed intake and hepatic cholesterol and lipid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


EGF receptor activation during allergic sensitization affects IL-6-induced T-cell influx to airways in a rat model of asthma.
EGF receptor (EGFR) is involved in cell differentiation and proliferation in airways and may trigger cytokine production by T cells. We hypothesized that EGFR inhibition at the time of allergic sensitization may affect subsequent immune reactions. Brown Norway rats were sensitized with OVA, received the EGFR tyrosine kinase inhibitor, AG1478 from days 0 to 7 and OVA challenge on day 14. OVA-specific IgE in serum and cytokines and chemokines in BAL were measured 24 h after challenge. To evaluate effects on airway hyperresponsiveness (AHR), rats were sensitized, treated with AG1478, intranasally challenged, and then AHR was assessed. Furthermore chemotactic activity of BALF for CD4(+) T cells was examined. The eosinophils, neutrophils and lymphocytes in BAL were increased by OVA and only the lymphocytes were reduced by AG1478. OVA significantly enhanced IL-6 concentration in BAL, which was inhibited by AG1478. However AHR, OVA-specific IgE and IL-4 mRNA expression in CD4(+) T cells were not affected by AG1478. BALF from OVA-sensitized/challenged rats induced CD4(+) T-cell migration, which was inhibited by both AG1478 treatment in vivo and neutralization of IL-6 in vitro. EGFR activation during sensitization may affect the subsequent influx of CD4(+) T cells to airways, mainly mediated through IL-6.


Detection of Solitary Pulmonary Nodules Based on Brain-Computer Interface.
Solitary pulmonary nodules are the main manifestation of pulmonary lesions. Doctors often make diagnosis by observing the lung CT images. In order to further study the brain response structure and construct a brain-computer interface, we propose an isolated pulmonary nodule detection model based on a brain-computer interface. First, a single channel time-frequency feature extraction model is constructed based on the analysis of EEG data. Second, a multilayer fusion model is proposed to establish the brain-computer interface by connecting the brain electrical signal with a computer. Finally, according to image presentation, a three-frame image presentation method with different window widths and window positions is proposed to effectively detect the solitary pulmonary nodules.


On the Rate of Boronate Ester Formation in ortho-Aminomethyl Functionalized Phenyl Boronic Acids.
The role of the ortho-aminomethyl functional group in phenyl boronic acids for sugar complexation is a topic of debate. To decipher its effect on the kinetics of boronate ester formation, we first performed pseudo-first order kinetics analyses at five pH values up to 4 mM in fructose, revealing a first-order kinetic dependence upon fructose. Under these conditions, the reaction is in equilibrium and does not reach completion, but at 50 mM fructose saturation is achieved revealing zero-order dependence upon fructose. This indicates rate-determining creation of an intermediate prior to reaction with fructose, which we propose involves leaving group departure of inserted solvent. Further, the region of kinetics displaying zero-order dependence has a kinetic isotope effect (KIE) of 1.42, showing involvement of a proton transfer in the leaving group departure. The ratio of forward and reverse rate constants branching from the intermediate shows that fructose is several thousand times more nucleophilic than the solvent. Overall, the data supports a mechanism where the o-aminomethyl group lowers the pK(a) of the proximal boronic acid and acts as a general-acid (as an ammonium) to facilitate leaving group departure. Consequently, by microscopic reversibility the resulting amine must perform general-base catalysis to deliver fructose.


CRISPR/Cas9-mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host-to-egg immune response.
Schistosomiasis is an important, neglected tropical disease. Schistosoma japonicum can evade host attacks by regulating the host's immunity, causing continuous infection. However, interactions between the host's immune system and S. japonicum are unclear. Our previous research found that the Sj16 protein isolated from S. japonicum has an anti-inflammatory effect in the host. However, the role of Sj16 in the regulation of host immunity in S. japonicum infection is not clear. Here, we applied the CRISPR/Cas9 technique to knockout Sj16 in S. japonicum eggs and investigated the effect of Sj16 in regulating host immunity. We found egg viability decreased after Sj16 knockout. In addition, we found granulomatous inflammation increased, the T-cell immune response enhanced and the immune microenvironment changed in mice model injected with Sj16-knockout eggs by tail vein. These findings suggested that S. japonicum could regulate host immunity through Sj16 to evade the host immune attack and cause continuous infection. In addition, we confirmed the application of CRISPR/Cas9-mediated gene reprogramming for functional genomics in S. japonicum.


Virulence of white spot syndrome virus (WSSV) isolates may be correlated with the degree of replication in gills of Penaeus vannamei juveniles.
A standardized inoculation model was used in 2 separate experiments to gauge the virulence of 3 white spot syndrome virus (WSSV) isolates from Thailand and Vietnam (WSSV Thai-1, WSSV Thai-2, and WSSV Viet) in Penaeus vannamei juveniles. Mortality patterns (Expt 1) were compared and WSSV-positive cells quantified (Expt 2) in tissues following intramuscular inoculation of shrimp with the most (WSSV Thai-1) and least (WSSV Viet) virulent isolates as determined by Expt 1. The results of Expt 1 demonstrated that mortalities began at 36 h post inoculation (hpi) for both Thai isolate groups and at 36 to 60 hpi for the Viet isolate group. Cumulative mortality reached 100% 96 to 240 h later in shrimp challenged with the WSSV Viet isolate compared to shrimp challenged with the Thai isolates. WSSV infection was verified in all groups by indirect immunofluorescence. In Expt 2, WSSV-infected cells were quantified by immunohistochemical analysis of both dead and time-course sampled shrimp. WSSV-positive cells were detected in tissues of Thai-1 inoculated dead and euthanized shrimp from 24 hpi onwards and from 36 hpi onwards in shrimp injected with the Viet isolate. Significantly more infected cells were found in tissues of dead shrimp inoculated with the Thai-1 than in Viet isolate-inoculated shrimp. In these experiments, substantial differences in virulence were demonstrated between the WSSV isolates. The Vietnamese isolate induced a more chronic disease and mortality pattern than was found for the Thai isolates, possibly because it infected fewer cells. This difference was most pronounced in gills.


Pluripotency Deconstructed.
Pluripotency denotes the flexible capacity of single cells to give rise to all somatic lineages and typically also the germline. Mouse ES cells and post-implantation epiblast-derived stem cells (EpiSC) are widely used pluripotent cell culture systems. These two in vitro stem cell types have divergent characteristics. They are considered as representative of distinct developmental stages, distinguished by using the terms "naïve" and "primed". A binary description is an over-simplification, however. Here, we discuss an intermediate stage of pluripotency that we term "formative". Formative pluripotency features a gene regulatory network switch from the naïve state and comprises capacitation of enhancers, signaling pathways and epigenetic machinery in order to install competence for lineage specification.


The contribution of diet and genotype to iron status in women: a classical twin study.
This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04).


Improved Methods for Determination of Petrophysical Properties of Unconventional Tight Rocks Using Particulate Samples.
Drill cuttings are available continuously over the entire depth of any drilled wells. The use of drill cuttings to obtain petrophysical data can add a significant value in formation evaluation. An update to the previous study is presented using NMR and Archimedes principle to determine petrophysical properties including porosity, bulk density, and matrix density from drill cuttings of organic-rich mudrock formations. In the original published method, sonication was used to clean and saturate the drill cutting samples. In this improved method, particulate samples were saturated using both sonication and pressure injection methods. The obtained results were compared with accepted lab measurement techniques. Results show that pressure saturation of particulate samples can provide accurate results of petrophysical properties. Obtaining reliable petrophysical data from drill cuttings can provide continuous and quasi-real-time data for the formation evaluation of reservoirs and can effectively reduce costs by reducing or eliminating expensive formation evaluation methods.


Activation of the double-stranded RNA (dsRNA)-activated human protein kinase in vivo in the absence of its dsRNA binding domain.
The interferon-induced, dsRNA-activated human protein kinase (PKR) exerts antiviral and antiproliferative effects through inhibition of protein synthesis. Studies of structure-function relationships in PKR have shown that two dsRNA binding motifs are important for its autophosphorylation and activation by dsRNA in vitro. To correlate these findings with the activity of PKR in vivo, we examined the function of various PKR deletion mutants in cultured cells by using an inducible expression system. In a reporter gene assay, mutant forms of the kinase lacking amino acids 1-97 (delta 1-97) and 104-157 (delta 104-157), which are required for dsRNA binding in vitro, retained full activity in vivo. Deletion of amino acids 233-271 (delta 233-271), however, abolished the translational inhibitory activity of the kinase and prevented its phosphorylation. Moreover, cells infected with vaccinia virus recombinants expressing wild-type PKR, the mutant delta 104-157, delta 186-222), developed almost complete inhibition of both viral and cellular protein synthesis was upon induction of PKR. This inhibition of viral protein synthesis was not observed in cells infected with a recombinant expressing delta 233-271 mutant PKR. Our findings establish that the region encompassing amino acids 233-271 of PKR is critical for kinase activity in vivo, whereas its dsRNA binding domain is dispensable.


Bilateral tension pneumothorax related to acupuncture.
We report on a patient with a rare case of bilateral tension pneumothorax that occurred after acupuncture. A 69-year-old large-bodied man, who otherwise had no risk factors for spontaneous pneumothorax, presented with chest pressure, cold sweats and shortness of breath. Immediately after bilateral pneumothorax had been identified on a chest radiograph in the emergency room, his blood pressure and percutaneous oxygen saturation suddenly decreased to 78 mm Hg and 86%, respectively. We confirmed deterioration in his cardiopulmonary status and diagnosed bilateral tension pneumothorax. We punctured his chest bilaterally and inserted chest tubes for drainage. His vital signs promptly recovered. After the bilateral puncture and drainage, we learnt that he had been treated with acupuncture on his upper back. We finally diagnosed a bilateral tension pneumothorax based on the symptoms that appeared 8 h after the acupuncture. Because the patient had no risk factors for spontaneous pneumothorax, no alternative diagnosis was proposed. We recommend that patients receiving acupuncture around the chest wall must be adequately informed of the possibility of complications and expected symptoms, as a definitive diagnosis can be difficult without complete information.


Rhodamine-inspired far-red to near-infrared dyes and their application as fluorescence probes.
Probes to dye for: Rhodamine-inspired Si-pyronine, Si-rhodamine, Te-rhodamine, and Changsha NIR dyes have been developed recently. These dyes show fluorescence in the far-red to near-infrared region, while retaining the advantages of the original rhodamines, such as high fluorescence quantum yield, tolerance to photobleaching, good water solubility, and exhibit great potential for biological application.


[Analytical method of guiqi mixture and its main ingredient Astragalus root].
Chuanxiog Rhizome, Chinese Angelica Root and Scrophularia Root in Guiqi mixture have been identified by TLC. A TLC-densitometric method for determining astragalosied in the patent medicine and its main ingredient Astragalus Root has been established. This method is sensitive and highly reproducible, with RSD under 3.0% and recovery over 98%.


T1 and T2 mapping in myocarditis: seeing beyond the horizon of Lake Louise criteria and histopathology.
Myocarditis and its sequelae remain an unconquered clinical problem, disproportionately affecting the young. Several hurdles beset myocarditis, including non-specific symptoms, heterogeneous clinical presentation, dynamic disease stages, underscored by an absence of an easy diagnostic test or a specific treatment. Areas covered: The current diagnostic means are poorly equipped to counter the challenge; the gold standard by invasive endomyocardial biopsy relies on availability of expert procedural and reading skill. The tissue diagnostic criteria were developed to improve readers agreement with clinical diagnosis, and not based on evidence for differential treatment or improved prognosis. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis. They require extensive imaging, which is insufficiently robust with poor diagnostic confidence and tissue pathophysiological validation; they similarly lack evidence of improved outcome by guiding clinical management. T1 and T2 mapping are a step-change, providing robust, short and quantifiable imaging application, which can veritably reflect the dynamic and heterogeneous underlying disease. Expert commentary: T1 and T2 mapping harbours a unique potential for an objective non-invasive disease recognition and treatment discovery in myocarditis. These measures should enter independently into clinical experimentation, with a high priority for outcome and therapeutic studies.


Partial recovery of delayed graft function due to cholesterol emboli after renal transplantation.
A 65-year-old man who received a deceased renal allograft in September 2001. The donor of the allograft was a 54-year-old hypertensive man who expired from intracerebral hemorrhage. Atheroma with hard plaques was present in both renal arteries and aortic patches. After vascular anastomosis and clamp release, the allograft recoloration was inadequate, and the patient remained anuric. Computerized tomography scan demonstrated disseminated infarction areas, suggesting cholesterol emboli, which was confirmed later by a graft biopsy. As approximately 50% of the renal parenchyma was perfused, graft nephrectomy was not indicated and dialysis was restarted. Diuresis was over 3000 ml/day and serum creatinine decreased and stabilized at 360 micromol/L by the 32nd postoperative day. The allograft supported the patient for only two years, and he eventually was successfully retransplanted in June 2003. We believe that delayed graft function due to cholesterol emboli disease may be reversible if areas of infarction are not too large.


Transfer and Expression of Native Human Insulin-Like Growth Factor-1 in Tobacco Chloroplasts.
Insulin-like growth factor-1 (IGF-1), in addition to having insulin-like effects, has boosting effects on all cells in human body. Most of the recombinant IGF-1 required for patients suffering from its deficiency is currently produced by bacterial and yeast systems. Plant systems, especially chloroplasts, have many benefits for producing human blood proteins. Production costs are low in these systems, and their side effects are less than other systems. In this study, the transfer and expression of mature IGF-1 protein cDNA in tobacco chloroplasts under the control of strong plastid transcription and translation elements was evaluated. The biolistic transformation method was used to transfer the IGF-1 gene cloned into the pRB94-IGF1 chloroplast vector. Homoplasmic transplastomic plants were produced through four selection rounds on the selective medium. Transfer of foreign genes to chloroplast genome was confirmed by PCR, Southern blotting and seed progeny test. RT-PCR and SDS-PAGE methods were used to evaluate the expression of IGF-1 gene in transgenic line. A truly transformed line was identified from selected seedlings by PCR method. The seed progeny test of 4th-regeneration-round transgenic plants of this line showed maternal inheritance and homoplasmic level for the selectable marker gene, which confirms the transfer and expression of the marker gene in the chloroplast genome. The Southern blot test also confirmed the transfer of the IGF-1 gene into the chloroplast genome. RT-PCR test showed that IGF-1 gene transcription is performed correctly in transgenic plants. Finally, accumulation of IGF-1 protein in transgenic plants was detected by SDS-PAGE. Successful transfer and expression of the native human IGF-1 gene in tobacco chloroplast genome is reported.


Identification of the CD45-associated 116-kDa and 80-kDa proteins as the alpha- and beta-subunits of alpha-glucosidase II.
CD45 is an abundant, highly glycosylated transmembrane protein-tyrosine phosphatase expressed on hematopoietic cells. Herein we demonstrate that two proteins of 116 kDa and 80 kDa copurify with CD45 from mouse T cells. Microsequence analysis of the 116-kDa protein revealed high similarity to an incomplete human open reading frame that has been suggested to correspond to the catalytic alpha-subunit of glucosidase II. We determined the nucleotide sequence of the mouse cDNA and observed that it encodes a protein product nearly identical to its human homologue and shares an active site consensus sequence with Family 31 glucosidases. Amino acid sequencing of the 80-kDa protein, followed by molecular cloning, revealed high homology to human and bovine cDNAs postulated to encode the beta-subunit of glucosidase II. Antisera developed to the mouse beta-subunit allowed us to demonstrate that the interaction between CD45 and glucosidase II can be reconstituted in vitro in an endoglycosidase H-sensitive manner. The strong interaction between glucosidase II and CD45 may provide a paradigm for investigating novel aspects of the biology of these proteins.


Androgen therapy in myelodysplastic syndromes with thrombocytopenia: a report on 20 cases.
Twenty patients with myelodysplastic syndromes (MDS) and (i) platelets < 50 x 10(9)/l and (ii) bone marrow blasts < or = 10% were treated with androgen therapy (fluoxymesterone at 1 mg/kg/d: seven patients; danazol at 600 mg/d: 13 patients) for at least 3 months. 11 of them (55%) had an increase in platelet counts by at least 30 x 10(9)/l and a disappearance of bleeding symptoms was seen in 6/6 patients with initial bleeding. A response with neutrophil counts (six cases) or haemoglobin levels (five cases) was less often seen. Treatment was continued for 3+ to 27 months in responders (the dose being reduced by 50% after 6 months). Seven patients on maintenance treatment were still responding. Another patient died while he was still responding, and the remaining three patients relapsed after discontinuation (two cases) and dose reduction to 50% (one case) of the androgen used. Side-effects of treatment were moderate. In our experience, androgen therapy can be useful in patients with 'low risks' MDS (i.e. with marrow blasts < or = 10%) and severe thrombocytopenia, especially because no growth factor regularly active on platelets is currently available.


Development of a low-temperature extrusion process for production of GRAS bioactive-polymer loaded compounds for targeting antimicrobial-resistant (AMR) bacteria.
Antimicrobial resistance (AMR) is recognised globally as one of the greatest threats to human and animal health; thus, discovery of alternative antibacterial agents to address AMR is a priority challenge. This study constitutes the first report of a low-melting temperature, polymer- extrusion process for the smart delivery of thermally-sensitive antimicrobial bioactives, including generally-regarded-as-safe (GRAS) bioactives derived from various sources. Bioactives were assessed before and after extrusion by determining their respective minimum inhibitory concentrations (MIC). WHO-priority AMR-bacterial isolates causing zoonotic infections were evaluated along with use of standard ATCC strains. Findings revealed that this copolymer method was capable of delivering thermally-sensitive bioactives with varying degrees of growth inhibition against the AMR-bacterial strains. The extrusion process was found to increase the effect of nisin against MRSA (4-fold increase) and L. monocytogenes (6.4-fold increase), silver nitrate (AgNO3) against E. coli (3.6-fold increase) and S. epidermidis (1.25-fold increase), and chitosan against S. aureus (1.25-fold). Findings show the potential applicability of this polymer extrusion process for developing future bioactive-loaded polymer compounds; thus, highlighting the potential of converging bio-based industry with novel materials for enabling 'One-Health' solutions.


History-dependent muscle resistance to stretch remains high after small, posturally relevant pre-movements.
The contributions of intrinsic muscle fiber resistance during mechanical perturbations to standing and other postural behaviors are unclear. Muscle short-range stiffness is known to vary depending on the current level and history of the muscle's activation, as well as the muscle's recent movement history; this property has been referred to as history dependence or muscle thixotropy. However, we currently lack sufficient data about the degree to which muscle stiffness is modulated across posturally relevant characteristics of muscle stretch and activation. We characterized the history dependence of muscle's resistance to stretch in single, permeabilized, activated, muscle fibers in posturally relevant stretch conditions and activation levels. We used a classic paired muscle stretch paradigm, varying the amplitude of a 'conditioning' triangular stretch-shorten cycle followed by a 'test' ramp-and-hold imposed after a variable inter-stretch interval. We tested low (<15%), intermediate (15-50%) and high (>50%) muscle fiber activation levels, evaluating short-range stiffness and total impulse in the test stretch. Muscle fiber resistance to stretch remained high at conditioning amplitudes of <1% optimal fiber length, L0, and inter-stretch intervals of >1 s, characteristic of healthy standing postural sway. An ∼70% attenuation of muscle resistance to stretch was reached at conditioning amplitudes of >3% L0 and inter-stretch intervals of <0.1 s, characteristic of larger, faster postural sway in balance-impaired individuals. The thixotropic changes cannot be predicted solely on muscle force at the time of stretch. Consistent with the disruption of muscle cross-bridges, muscle resistance to stretch during behavior can be substantially attenuated if the prior motion is large enough and/or frequent enough.


Late-onset neonatal sepsis: recent developments.
The incidence of neonatal late-onset sepsis (LOS) is inversely related to the degree of maturity and varies geographically from 0.61% to 14.2% among hospitalised newborns. Epidemiological data on very low birth weight infants shows that the predominant pathogens of neonatal LOS are coagulase-negative staphylococci, followed by Gram-negative bacilli and fungi. Due to the difficulties in a prompt diagnosis of LOS and LOS-associated high risk of mortality and long-term neurodevelopmental sequelae, empirical antibiotic treatment is initiated on suspicion of LOS. However, empirical therapy is often inappropriately used with unnecessary broad-spectrum antibiotics and a prolonged duration of treatment. The increasing number of multidrug-resistant Gram-negative micro-organisms in neonatal intensive care units (NICU) worldwide is a serious concern, which requires thorough and efficient surveillance strategies and appropriate treatment regimens. Immunological strategies for preventing neonatal LOS are not supported by current evidence, and approaches, such as a strict hygiene protocol and the minimisation of invasive procedures in NICUs represent the cornerstone to reduce the burden of neonatal LOS.