Cholesterol depletion inhibits store-operated calcium currents and exocytotic membrane fusion in RBL-2H3 cells.
The effects of cholesterol depletion from the plasma membrane with methyl-beta-cyclodextrin (MbetaCD) on exocytotic processes were investigated in rat basophil leukemia cells (RBL-2H3 cells). Pretreatment of the cells with MbetaCD inhibited antigen-evoked exocytotic release dose-dependently. To elucidate the mechanism of this inhibition, we performed experiments on the effects of MbetaCD on exocytotic membrane fusion and mobilization of Ca(2+) and on the localization of the tyrosine kinase Lyn. Inhibition of degranulation by MbetaCD was observed even under stimulation with the phorbol ester and calcium ionophore. Therefore, MbetaCD affected a process downstream of Ca(2+) influx, or membrane fusion between the granule and the plasma membrane. Intracellular calcium measurements revealed that MbetaCD inhibited the Ca(2+) increase induced by antigen. Furthermore, we found that MbetaCD significantly inhibited Ca(2+) influx from the extracellular medium through the store-operated calcium channel (SOC) but did not affect Ca(2+) release from the intracellular Ca(2+) store. Fluorescent image analysis of cells expressing Lyn-YFP showed that treatment with MbetaCD scarcely affected the localization and lateral mobility of Lyn in the plasma membrane. These results suggest that cholesterol depletion by MbetaCD decreases degranulation mainly by inhibiting the SOC and membrane fusion between the secretory granules and the plasma membrane in mast cells.


Template-Directed Synthesis of Porous and Protective Core-Shell Bionanoparticles.
Metal-organic frameworks (MOFs) are promising high surface area coordination polymers with tunable pore structures and functionality; however, a lack of good size and morphological control over the as-prepared MOFs has persisted as an issue in their application. Herein, we show how a robust protein template, tobacco mosaic virus (TMV), can be used to regulate the size and shape of as-fabricated MOF materials. We were able to obtain discrete rod-shaped TMV@MOF core-shell hybrids with good uniformity, and their diameters could be tuned by adjusting the synthetic conditions, which can also significantly impact the stability of the core-shell composite. More interestingly, the virus particle underneath the MOF shell can be chemically modified using a standard bioconjugation reaction, showing mass transportation within the MOF shell.


Smoking Cessation Counseling in Practice: A Qualitative Analysis of Quitline Conversations in Queensland, Australia.
Telephone-based services are a practical and effective behavioral support for smoking cessation, yet no in-depth analyses of this counseling have been conducted. Understanding the general content of Quitline conversations can help to improve current practices and may inform future interventions. Therefore, we aimed to independently explore conversation themes, topics, and client questions during Quitline counseling sessions with Quitline clients in Queensland, Australia. A purposive sample of 30 recorded counseling sessions, completed between January and March 2019, were de-identified, transcribed, and thematically analyzed. Seven themes, encompassing 35 topics, were derived from 26 initial calls and four follow-up calls: (1) Client details and building rapport; (2) Client history and motivation to quit; (3) Pharmacotherapy; (4) Behavioral aspects of quitting and relationship with smoking; (5) Understanding nicotine dependence and other important considerations; (6) Additional support and smoking cessation resources; and (7) Planning, goal setting and follow-up. Three themes emerged from 18 client questions including (1) Pharmacotherapy safety and contraindications; (2) Pharmacotherapy instructions and mechanism of action; and (3) Physiology of nicotine dependence. This is the first qualitative analysis of the content of Quitline counseling sessions in Australia. Counselors collect and deliver a breadth of information to provide tailored, evidence-based health care, while building rapport and trust. Findings may be translatable into personalized self-help interventions that are more accessible or appealing to people reluctant to contact Quitline. Harnessing educational opportunities regarding pharmacotherapy adherence and misconceptions can improve client confidence in the product and smoking cessation outcomes. Further research will map conversations to motivational interviewing and behavior change techniques.


The 15-Minute Family Interview as a learning strategy for senior undergraduate nursing students.
Nursing care of families continues to be a challenge within complex and demanding health-care systems. Educational strategies to bridge the theory-practice gap, connecting classroom learning with clinical experiences in undergraduate nursing education, enable students to develop the skills required to form meaningful partnerships with families. This article describes how undergraduate nursing students complete a 15-Minute Family Interview in a clinical practice setting, and document the interview process in a reflective major paper. Students integrate research and theory and identify ways to improve the care of families in the clinical setting while building communication skills and confidence in interacting with families in everyday practice. The implementation of the assignment and the evaluation of the process, including quotes from 10 student papers and 2 clinical faculty members, are discussed. Implications for education and ongoing research are offered.


Adaptation of Listeria monocytogenes in a simulated cheese medium: effects on virulence using the Galleria mellonella infection model.
The aim of this study was to evaluate the effect of the acid and salt adaptation in a cheese-based medium on the virulence potential of Listeria monocytogenes strains isolated from cheese and dairy processing environment using the Galleria mellonella model. Four L. monocytogenes strains were exposed to a cheese-based medium in conditions of induction of an acid tolerance response and osmotolerance response (pH 5·5 and 3·5% w/v NaCl) and injected in G. mellonella insects. The survival of insects and the L. monocytogenes growth kinetics in insects were evaluated. The gene expression of hly, actA and inlA genes was determined by real-time PCR. The adapted cells of two dairy strains showed reduced insect mortality (P < 0·05) in comparison with nonadapted cells. Listeria monocytogenes Scott A was the least virulent, whereas the cheese isolate C882 caused the highest insect mortality, and no differences (P > 0·05) was found between adapted and nonadapted cells. The gene expression results evidenced an overexpression of virulence genes in cheese-based medium, but not in simulated insect-induced conditions. Our results suggest that adaptation to low pH and salt in a cheese-based medium can affect the virulence of L. monocytogenes, but this effect is strain dependent. In this study, the impact of adaptation to low pH and salt in a cheese-based medium on L. monocytogenes virulence was tested using the Wax Moth G. mellonella model. This model allowed the differentiation of the virulence potential between the L. monocytogenes strains. The effect of adaptation on virulence is strain dependent. The G. mellonella model revealed to be a prompt method to test food-related factors on L. monocytogenes virulence.


Routine laboratory parameters in patients with necrotizing pancreatitis by the time of operative pancreatic debridement: Food for thought.
Timing of invasive intervention such as operative pancreatic debridement (OPD) in patients with acute necrotizing pancreatitis (ANP) is linked to the degree of encapsulation in necrotic collections and controlled inflammation. Additional markers of these processes might assist decision-making on the timing of surgical intervention. In our opinion, it is logical to search for such markers among routine laboratory parameters traditionally used in ANP patients, considering simplicity and cost-efficacy of routine laboratory methodologies. To evaluate laboratory variables in ANP patients in the preoperative period for the purpose of their use in the timing of surgery. A retrospective analysis of routine laboratory parameters in 53 ANP patients undergoing OPD between 2017 and 2020 was performed. Dynamic changes of routine hematological and biochemical indices were examined in the preoperative period. Patients were divided into survivors and non-survivors. Survivors were divided into subgroups with short and long post-surgery length of stay (LOS) in hospital. Correlation analysis was used to evaluate association of laboratory variables with LOS. Logistic regression was used to assess risk factors for patient mortality. Seven patients (15%) with severe acute pancreatitis (SAP) and 46 patients (85%) with moderately SAP (MSAP) were included in the study. Median age of participants was 43.2 years; 33 (62.3%) were male. Pancreatitis etiology included biliary (15%), alcohol (80%), and idiopathic/other (5%). Median time from diagnosis to OPD was ≥ 4 wk. Median postoperative LOS was at the average of 53 d. Mortality was 19%. Progressive increase of platelet count in preoperative period was associated with shortened LOS. Increased aspartate aminotransferase and direct bilirubin (DB) levels the day before the OPD along with weak progressive decrease of DB in preoperative period were reliable predictors for ANP patient mortality. Multifactorial analysis of dynamic changes of routine laboratory variables can be useful for a person-tailored timing of surgical intervention in ANP patients.


Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: a pilot study.
Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.


Low-impact chemical weed control techniques in UNESCO World Heritage Sites of Cuba.
Dichrostachys cinerea is a thorny, acacia-like, fast-growing woody bush which invades fields, wasteland, road sides and other disturbed areas. This gregarious species has become a very aggressive invasive weed in Cuba, where no native predators or pathogens are found. It often encroaches in fallows, overgrazed areas and mismanaged veld. D. cinerea is a very difficult weed to eliminate because of its active suckering, and is liable to produce dense thickets which are quite impenetrable on account of the density and abundance of its long, stiff, sharp thorns. In the Valle de los Ingenios area (Cuba Central), the tree is unchecked and forms veritable forests in areas on which cane growing has been discontinued. Physical management by cutting and burning the plants is not a very efficient control method, since the seeds survive in the soil, and they grow very fast. Therefore, chemical methods via the use of herbicides are often necessary to eradicate this weed. A preliminary study using glyphosate and auxin-like herbicides (2,4-D + picloram, MCPA, and MCPA + 2,4-D) plus adjuvants has been carried out in order to elucidate the best mixtures rendering maximum weed control with minimum herbicide rate and environmental stress. None of the herbicides used except glyphosate and 2,4-D + picloram showed acceptable mortality rates (75-80%) at the recommended doses tested. In the failed herbicide treatments, only the use of double herbicide rates succeeded in controlling marabou. The herbicide mixture of 2,4-D + picloram formulated with either a non-ionic surfactant or a mixture of fatty acid esters was the best option to control D. cinerea in terms of maximum effectiveness and minimum environmental stress, as the reduction in active ingredients applied to the environment was x3 in these two adjuvant-amended formulations compared to 2,4-D + picloram alone.


High recovery of mesenchymal progenitor cells with non-density gradient separation of human bone marrow.
Bone marrow (BM) is the most used source of hemopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) in both hematologic settings and regenerative medicine. We compared the feasibility and reproducibility of two gravity separation techniques, with or without the use of a density gradient, in terms of both hematopoietic and mesenchymal human BM progenitors. A total of 16 BM samples was processed to obtain mononuclear cells (MNC) and buffy coats (BC). The efficiency of the two procedures was evaluated by recovery of white blood cells (WBC), MNC and CD34(+) cells, clonogenic assays, red blood cell (RBC) depletion, cell viability, expression of embryonic transcriptional regulators and MSC assessment. The two procedures yielded a comparable recovery of HSC. Non-density gradient separation (NDGS) of BM resulted in four times higher MSC recovery and higher expression of embryonic stem cell markers (Nanog and Sox2) compared with density-gradient separation (DGS). MSC derived from both procedures was comparable in terms of phenotype, differentiation and proliferation potential. NDGS is less time consuming, provides a better MSC enrichment and appears to be a suitable cell preparation method for clinical applications.


Construction, purification and biological activities of recombinant human interleukin-2 analogs.
Fourteen human interleukin-2 (IL-2) analogs have been cloned and expressed in E. coli, starting from a chemically synthesized gene for human IL-2 optimized for expression in E. coli. These analogs were purified to greater than 95% purity as determined by SDS-PAGE, and were measured for biological activity in a 3H-thymidine incorporation assay using an IL-2 dependent murine T-cell line (CTLL). One analog was made which eliminated the N-terminal 23 amino acids from the protein by replacing one restriction endonuclease fragment with another. This analog, which begins at an internal methionine, had no detectable CTLL activity. Thirteen analogs were constructed using oligonucleotide site-directed mutagenesis. Four of these analogs were truncated at various residues near the C-terminus (residues 106, 116, 121 and 126). These analogs had at least 500-fold lower CTLL activities than the natural recombinant IL-2. The remaining nine analogs had substitutions at 1, 2, or all 3 of the three cysteine residues in the protein (residues 58, 105 and 125). Substituting an alanine, asparagine, aspartic acid, or serine at residue 125 resulted in highly active molecules with CTLL activities similar to that of the natural recombinant IL-2. The analogs with alanine and serine substitutions at residue 125 actually had slightly higher CTLL activities than the natural recombinant IL-2. Substituting alanine for cysteine at position 125 and serine for cysteine at either position 58 or 105 yielded analogs with about 150-fold lower CTLL activities than natural recombinant IL-2. Substituting an alanine for the cysteine at position 125 and serines for cysteines at both positions 58 and 105 resulted in an analog with 30-fold lower CTLL activity than the natural recombinant IL-2. The ten analogs with less than 1.0% of the CTLL activity of natural recombinant IL-2 were tested for competition with the natural recombinant IL-2 by mixing a 10-to 100- fold excess of the analog with the natural recombinant IL-2 and assaying the mixture in the CTLL assay. None of these analog mixtures resulted in a lower activity than mixing the natural recombinant IL-2 with buffer alone, implying that none of these analogs effectively competes with the natural recombinant IL-2 for binding to IL-2 receptors during incubation with the CTLL cells. If reduced binding does occur, it may be the direct cause of their lower activities.


[5-10-year results with the straight-shaft Müller prosthesis].
103 patients with 106 Müller straight stem prostheses could be evaluated clinically and radiologically after an average follow-up period of 6.8 years (range 5 to 10 ys.). Although until now no revision for aseptic loosening has become necessary 3 p.c. of the stems and 11 p.c. of the acetabular components showed radiological loosening. The clinical results were rated as satisfactory. After surgery 67 p.c. of the patients were completely painfree, 28 p.c. still had slight pain, 4 p.c. moderate and 1 p.c. severe pain. The investigation concentrated particularly on radiographic changes of the interface of the femur. Whereas radiolucency typically was non-progressive and located in the proximal part of the femur we found an increasing atrophy of the cortical bone on the calcar. Moreover, we found a continuous and increasing subsidence of the stem during the whole period of observation. At the time of follow up 56 p.c. of the straight stems had subsided about 2 mm and more. Calcar atrophy and radiolucency were significantly less present in femurs with a tapered medullary canal than in those with a cylindrical shape.


Carbon-Dots-Based Lab-On-a-Nanoparticle Approach for the Detection and Differentiation of Antibiotics.
Fluorescent carbon dots (CDs) have received considerable attention in recent years due to their superior optical properties. To take further advantages of these unique features, herein, a CDs-based "lab-on-a-nanoparticle" approach for the detection and discrimination of antibiotics is developed. The sensing platform was designed based on the different channel's fluorescence recoveries or further quenching of the full-color emissive CDs (F-CDs) and metal ion ensembles upon the addition of antibiotics. The F-CDs exhibited unusually comparable emission intensity nearly across the entire visible spectrum even as the excitation wavelength is shifted, making it very suitable for the construction of multi-channel sensing systems. The sensing platform was fabricated on the basis of the competing interaction of metal ions with the F-CDs and antibiotics. Three metal ions (i.e., Cu2+ , Ce3+ and Eu3+ ) can efficiently quench the fluorescence of the F-CDs. Upon the addition of antibiotics, the fluorescent intensities either recovered at different emission wavelengths or were further quenched to various degrees. The fluorescence response patterns at different emission wavelength were characteristic for each antibiotic and can be quantitatively differentiated by standard statistical methods (e.g., hierarchical clustering analysis and principal component analysis). Moreover, as an example, the proposed method was applied for quantitative detection of oxytetracycline with a limit of detection to be 0.06 μm. Finally, the sensing system was successfully employed for residual antibiotics detection and identification in real food samples.


A novel role for ketoconazole in hepatocellular carcinoma treatment: linking PTGS2 to mitophagy machinery.
Ketoconazole is a broad-spectrum antifungal agent, which has recently been characterized as a potential anticancer agent in several cancer types. However, the molecular mechanism underlying the anticancer effect of ketoconazole is not clearly defined. Our recent findings demonstrate that ketoconazole suppresses the growth of hepatocellular carcinoma (HCC) cells by exacerbating mitophagy in vitro and in vivo. Mechanistically, PINK1-PRKN-mediated mitophagy are led by ketoconazole-induced suppression of PTGS2 (prostaglandin-endoperoxide synthase 2), which in turn results in mitochondrial dysfunction and consequent apoptosis. These data link PTGS2 to mitophagy machinery and implicate ketoconazole as a potential therapeutic option for HCC treatment.


Individual-level precision diagnosis for coronavirus disease 2019 related severe outcome: an early study in New York.
Because of inadequate information provided by the on-going population level risk analyses for Coronavirus disease 2019 (COVID-19), this study aimed to evaluate the risk factors and develop an individual-level precision diagnostic method for COVID-19 related severe outcome in New York State (NYS) to facilitate early intervention and predict resource needs for patients with COVID-19. We analyzed COVID-19 related hospital encounter and hospitalization in NYS using Statewide Planning and Research Cooperative System hospital discharge dataset. Logistic regression was performed to evaluate the risk factors for COVID-19 related mortality. We proposed an individual-level precision diagnostic method by taking into consideration of the different weights and interactions of multiple risk factors. Age was the greatest risk factor for COVID-19 related fatal outcome. By adding other demographic variables, dyspnea or hypoxemia and multiple chronic co-morbid conditions, the model predictive accuracy was improved to 0.85 (95% CI 0.84-0.85). We selected cut-off points for predictors and provided a general recommendation to categorize the levels of risk for COVID-19 related fatal outcome, which can facilitate the individual-level diagnosis and treatment, as well as medical resource prediction. We further provided a use case of our method to evaluate the feasibility of public health policy for monoclonal antibody therapy.


Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability.
To determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD). We conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects. All 3 doses of intranasal oxytocin were safe and well tolerated. A multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD. This study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory.


National Health Service Corps staffing and the growth of the local rural non-NHSC primary care physician workforce.
Beyond providing temporary staffing, National Health Service Corps (NHSC) clinicians are believed by some observers to contribute to the long-term growth of the non-NHSC physician workforce of the communities where they serve; others worry that NHSC clinicians compete with and impede the supply of other local physicians. To assess long-term changes in the non-NHSC primary care physician workforce of rural underserved counties that have received NHSC staffing support relative to workforce changes in underserved counties without NHSC support. Using data from the American Medical Association and NHSC, we compared changes from 1981 to 2001 in non-NHSC primary care physician to population ratios in 2 subsets of rural whole-county health professional shortage areas: (1) 141 counties staffed by NHSC physicians, nurse practitioners, and/or physician assistants during the early 1980s and for many of the years since and (2) all 142 rural health professional shortage area counties that had no NHSC clinicians from 1979 through 2001. From 1981 to 2001, counties staffed by NHSC clinicians experienced a mean increase of 1.4 non-NHSC primary care physicians per 10,000 population, compared to a smaller, 0.57 mean increase in counties without NHSC clinicians. The finding of greater non-NHSC primary care physician to population mean ratio increase in NHSC-supported counties remained significant after adjusting for baseline county demographics and health care resources (P < .001). The estimated number of "extra" non-NHSC physicians in NHSC-supported counties in 2001 attributable to the NHSC was 294 additional physicians for the 141 supported counties, or 2 extra physicians, on average, for each NHSC-supported county. Over the 20 years, more NHSC-supported counties saw their non-NHSC primary care workforces grow to more than 1 physician per 3,500 persons, but no more NHSC-supported than nonsupported counties lost their health professional shortage area designations. These data suggest that the NHSC contributed positively to the non-NHSC primary care physician workforce in the rural underserved counties where its clinicians worked during the 1980s and 1990s.


Reconstruction with a 180-degree Rotationally Divided Latissimus-dorsi-musculocutaneous Flap after the Removal of Locally Advanced Breast Cancer.
This study described a technique for reconstruction of a large lateral thoracic region defect after locally advanced breast cancer resection that allows for full coverage of the defect and primary closure of the flap donor site. The authors performed reconstruction using the newly designed 180-degree rotationally-divided latissimus-dorsi-musculocutaneous flap in a 42-year-old woman for coverage of a large skin defect (18 × 15 cm) following extensive tissue resection for locally advanced breast cancer. The latissimus-dorsi-musculocutaneous flap, consisting of two rotated skin islands (18 × 7.5 cm each) that were sutured to form a large skin island, was used for coverage of the defect. The flap was sutured without causing excessive tension in the recipient region and the donor site was closed with simple reefing. No skin grafting was necessary. The flap survived completely, shoulder joint function was intact, and esthetic outcome was satisfactory. Quick wound closure allowed postoperative irradiation to be started 1 month after surgery. The technique offered advantages over the conventional pedicled latissimus-dorsi-musculocutaneous flap, but the flap was unable to be used, when the thoracodorsal artery and vein were damaged during extensive tissue removal. Detailed planning before surgery with breast surgeons would be essential.


[Effect of amizil and the ACTH4-10 fragment on the ability of mice to extrapolate the direction of movement].
Mice possessing the ability to extrapolate the direction of movement (100% of correct choices) were injected i.p. with different doses of m-cholinolytic amizil 2 hours before experiment. Doses of 2-5 mg/kg reduced the percentage of correct choices, the adequate solving strategy being replaced by stereotyped unidirectional reactions or stereotyped alternating responses. Doses of 8-12 mg/kg induced "refusals" to solve extrapolation problem. When amizil treated mice were intraventricularly injected with 1 mg/kg of ACTH4-10, their extrapolation ability was restored. This compensatory action of peptide could be mediated by its influence on cholinergic as well as on other neurotransmitter systems.


The mouse plasma PAF acetylhydrolase: II. It consists of two enzymes both associated with the HDL.
The PAF acetylhydrolase (PAF-AH) of mouse plasma was characterised as to its lipoprotein subclass and apolipoprotein association. Association with plasma lipoproteins was established by cholesteryl-hemisuccinate agarose affinity chromatography while electrophoretic and electrofocusing studies demonstrated almost exclusive association with the HDL-VHDL. Fractionation of [4-14C]cholesterol-labelled plasma on a Bio-Gel A-5m column established that 1% of the enzymic activity was associated with the VLDL-LDL, 4.5% with the HDL1, 80% with the HDL2-HDL3 and 15% with the VHDL. Electrophoresis of the solubilised, HDL2-HDL3 bound enzyme gave two peaks of activity with mobilities of 0.29 and 0.49 and a distribution of the recovered activity of 78 and 22%, respectively. The VHDL associated activity on similar analysis gave a 25 and 75% distribution. These findings showed that two enzymes, both associated with the HDL and VHDL fractions, constitute the PAF-AH activity of mouse plasma. Further fractionation of the HDL2-HDL3 bound activity on heparin-agarose established that 70% of the recovered activity was bound to the apo-E containing HDL.


SERPINH1 enhances the malignancy of osteosarcoma via PI3K-Akt signaling pathway.
Serpin Family H Member 1 (SERPINH1) may be involved in the regulation of occurrence and development of tumors. However, the role and mechanism of SERPINH1 in osteosarcoma remain poorly understood. The aim of this study is to investigate the expression and role of SRPINH1 in osteosarcoma and to elucidate its underlying mechanisms. First, we examined the expression of SERPINH1 in osteosarcoma and analyzed publicly available datasets to investigate whether SERPINH1 expression was associated with the prognosis of osteosarcoma. Then we constructed SERPINH1 overexpression and knockdown systems in osteosarcoma cells, and examined the proliferation, migration and invasion ability of osteosarcoma cells after SERPINH1 expression changes using CCK-8 assay, wound healing assay and transwell invasion assay. In addition, we constructed a subcutaneous xenograft tumor model to study the function of SERPINH1 in vivo. We also examined the downstream pathways of SERPINH1 by functional analysis and performed subsequent validation. SERPINH1 was upregulated and associated with poor survival in patients with osteosarcoma. SERPINH1 promoted the proliferation, migration and invasion of osteosarcoma cells and promotes the growth of osteosarcoma in vivo by activating the PI3K-Akt signaling pathway. SERPINH1 partakes in the biological process of osteosarcoma as a tumor promotor and may be an emerging biomarker in osteosarcoma.


Alternative Route Triggering Multistep Spin Crossover with Hysteresis in an Iron(II) Family Mediated by Flexible Anion Ordering.
Multistep spin crossover (SCO) compounds have attracted much attention, since they can be great candidates for high-density multinary memory devices. The introduction of substituents, such as methyl (Me), chloro (Cl), bromo (Br), and methoxy (MeO) groups, at para positions to the phenyl-substituted tripodal N6 ligand-coordinated SCO FeII material, [FeLPh](NTf2)2 [where LPh = tris(2-{[(1-phenyl-1H-1,2,3-triazol-4-yl)methylidene]amino}ethyl)amine and NTf2 = bis(trifluoromethanesulfonyl)imide], affords a new family of solvent-free FeII complexes: [FeL4-R-Ph](NTf2)2 {where L4-R-Ph = tris[2-({[1-(4-R-phenyl)-1H-1,2,3-triazol-4-yl]methylidene}amino)ethyl]amine, where R = Me (1), Cl (2), Br (3), and MeO (4)}. 1 shows temperature invariant high-spin (HS) state, whereas the others show spin transitions with different characteristics, such as half-SCO (4), two-step SCO (3), and unusual three-step SCO with hysteresis (2). Mössbauer and X-ray absorption fine structure (XAFS) spectroscopic studies of them support the magnetic susceptibilities results. Density functional theory calculations indicate that the electronic effect of different substituents on magnetic properties is negligible in this FeII family. Single-crystal X-ray diffraction studies reveal that 1-4 has a similar packing arrangement with three-dimensional supramolecular network via intermolecular π-π and CH···π interactions between complex cations, and CH···X (X = O, N, and F) hydrogen bonding interactions between cations and inherently frustrated NTf2 anions. Variable-temperature structural studies unveil a variety of stepped SCO behaviors of 2-4 and deactivation of SCO in 1 are governed by the regulation of ordering of NTf2 counteranions through the subtle modification of terminal substituents of complex cations. Quantitative light-induced excited spin-state trapping (LIESST) effect was observed for 2-4 via green light irradiation (532 nm) at 10 K. This study opens up a new way for systematic control of magnetic response from no SCO to half-, two-step, and finally three-step SCO with hysteresis by precise tuning of the ordering of flexible NTf2 anions included in the supramolecular network with potentially SCO-active complex cations.


Polymorphic ecthymatoid dermosporidiosis.
We report the case of a young Chhattisgarhi male with polymorphic dermosporidiosis (cutaneous rhinosporidiosis). He had multiple subcutaneous nodules and an ecthymatoid skin lesion along with nasal rhinosporidiosis. The diagnosis was confirmed by demonstration of sporangia with endospores in fine-needle aspiration cytology (FNAC), histopathology, and imprint smear from the skin lesions. Treatment was by surgical excision, electrocoagulation, and dapsone. There was no recurrence. Dermatologists should be aware of the diverse cutaneous manifestations of this primarily nasal disease. This is the second published report of polymorphic dermosporidiosis, and the first one reporting an ecthymatoid lesion.


Hyperfine coupling in methyl radical isotopomers.
The hyperfine coupling constants (hfcs) of two methyl radical isotopomers, CH2Mu and CD2Mu, have been measured over a wide range of temperature in ketene and ketene-d2, from which the radicals were generated. The magnitudes of the hfcs of these muoniated methyl radical isotopomers are larger than those of CH3 and CD3 due to larger zero-point energy in the out-of-plane bending mode. In contrast to CH3 and CD3, where the coupling constants become smaller with increasing temperature, the negative hfcs of the muoniated radicals were found to increase in magnitude (become more negative) with temperature, passing through a maximum near the boiling point of ketene. This behavior is attributed to a solvent-induced change in the force constant of the out-of-plane bending mode. The opposite temperature effect known for CH3 and CD3 is explained by excitation of the low frequency out-of-plane bending mode. This effect is much smaller in the muoniated radicals, where the vibrational frequency is significantly higher due to the light mass of muonium; consequently, the solvent effect dominates at low temperatures.


Benign monoclonal gammopathy presenting with severe renal failure.
A patient with monoclonal gammopathy and renal failure due to kappa light chain deposition in the glomerular basement membrane is reported. After 8 months, he developed a progressive and severe renal failure requiring haemodialysis. 30 months later, the monoclonal gammopathy was unchanged. Clinical features, as well as kinetic and immunological studies, were consistent with a diagnosis of benign monoclonal gammopathy (BMG). This case suggests that the renal failure complicating a monoclonal gammopathy is not related to its malignancy.


Balancing potential risks and benefits of hemoglobin-based oxygen carriers.
Hemoglobin-based oxygen carriers (HBOCs) are thought to have an adverse risk:benefit profile when compared to that of transfusing stored red blood cells (RBCs). However, there are clinical circumstances when RBC transfusion is not an option (e.g., patient refusal, unavailability owing to issues of compatibility or remote location). For these circumstances assessment of the risks of an HBOC should be compared to the risks of untransfused acute anemia. In this article we compare the risk of allowing a patient with severe anemia to have a further small decrease in hemoglobin (Hb) concentration to the risk of infusing an HBOC. We conclude that at Hb concentrations less than 6 g/dL, the risk of a further decrease in Hb concentration greatly exceeds the risk of HBOC infusion. Thus, we suggest that there may be a place for use of HBOCs when RBC transfusion is not an option.


Photoreaction of furocoumarins with DNA is similarly inhibited by minor and major groove-interacting ligands.
It was found that methyl green, a major groove binding ligand and the minor groove binding ligands, netropsin and 2,7-di-tert-butylproflavine inhibit, to a similar extend a monoadduct forming benzopsoralen and monoadduct and diadduct forming derivatives of psoralen (8-methoxypsoralen and 3,4'-dimethyl-8-methoxypsoralen). Caffeine exhibits an inhibitory effect on furocoumarin photobinding to DNA at 10(3) fold higher concentration. Together with the previously published results it is concluded that both occupancy of the major and minor groove as well as intercalation hinder photobinding of furocoumarins to DNA.


Arthrodesis of the first metatarsophalangeal joint.
Arthrodesis has emerged as the primary salvage procedure for severe osteoarthritis of the first metatarsophalangeal (MTP) joint. Forty-three patients underwent arthrodesis of the first MTP joint with stabilization provided by either 2 crossed lag-screws or a dorsal plate and screws. First MTP joint arthrodesis was the primary procedure for 46 of the 54 treated feet. Joint surfaces were shaped into a ball-and-socket configuration to augment joint surface contact and facilitate alignment for arthrodesis. Postoperative care involved using a compressive bandage, a surgical shoe, and a cane, crutches, or a walker. Partial weight-bearing was allowed immediately after surgery. Few casts were used postoperatively. At a mean of 21.7 months (median, 13.5 months), 34 of the 43 patients completed a brief telephone survey about surgical outcomes. Radiographic measurements of intermetatarsal, hallux valgus, inclination, and dorsiflexion angles were made preoperatively and postoperatively. Mean time to fusion was 7.3 weeks; arthrodesis was successful for 50 of 52 feet (radiographs were missing for 2 of the 54 feet treated). Internal fixation devices were removed from 5 feet. Thirty (88.2%) of the 34 patients rated their result as excellent or good; the other 4 (11.8%) rated their result as poor.


A continuous, spectroscopic analysis of the kinetics of elastase secretion by neutrophils. The dependence of secretion upon receptor occupancy.
We have developed a continuous spectroscopic method to analyze the kinetics of elastase secretion by human neutrophils. We have used the elastase-specific substrate methylsuccinylalanylalanylprolylvalylmethylcoumarin amide (Castillo, M. J., Nakajima, K., Zimmerman, J., and Powers, J. C. (1979) Anal. Biochem. 99, 53-64), which liberates the fluorophore, aminomethylcoumarin, when cleaved by elastase. We find that secretion of elastase in cytochalasin B-treated cells is initiated within approximately 5 s of exposure of the cells to the fluoresceinated chemotactic peptide stimulus, N-formyl-norleucylleucylphenylalanylnorleucyltyrosyllysine-fluorescein, and that secretion is completed within 30 s. The kinetics of this response is only slightly dependent on the concentration of the stimulus. Up to 100% (approximately 0.5 pg/neutrophil) of the elastase can be released in a dose-dependent manner by stimulated cells. We have also used this fluoresceinated stimulus and an antibody to fluorescein (Sklar, L. A., Oades, Z. G., Jesaitis, A. J., Painter, R. G., and Cochrane, C. G. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 7540-7544) to probe the temporal relationship between the binding of stimulus to the receptors and the cellular response. We find that the entire response is elicited by the binding which occurs within the first 15 s after the addition of stimulus, regardless of the dose. We estimate that an occupancy of no more than 20% of the cellular receptors for the stimulus is required to evoke the optimal response.


[Non-parasitic liver cysts: laparoscopic and conventional fenestration].
From 1992 till 1997 10 patients with solitary non-parasitic liver cysts were treated by laparoscopically fenestration of the cysts. The size of the cysts varied between 8 and 16 cm (median 13.5). Conversion to laparotomy was required in one patient because of intraoperative bleeding. In nine patients the laparoscopic procedure was finished successfully. In these cases we observed no intraoperative complications (9/10), intraoperative blood loss amounted up to 100 ml. Median operative time amounted to 82.5 minutes (55-155). No postoperative complications were observed. In two patients a cystadenoma was proven by postoperative histology, in both cases a liver resection was performed. During a median follow-up of 33 (2-43) months 2 of 7 patients treated with laparoscopically fenestration developed a recurrence (28%).


Congenital vertebral anomalies: aetiology and relationship to spina bifida cystica.
A family survey of 337 patients with congenital vertebral anomalies has been carried out from the Scoliosis Clinics of Edinburgh and the Royal National Orthopaedic Hospital, London. From genetic and epidemiological evidence it is clear that multiple vertebral anomalies (without apparent spina bifida) are aetiologically related to anencephaly and spina bifida cystics, carrying a 5-10% risk to subsequent sibs for any one of these defects. The implications for prenatal diagnosis are discussed. Solitary hemivertebrae and localized anterior defects of the vertebral bodies causing kyphoscoliosis are sporadic (non-familial) in nature, carrying no risk to subsequent sibs.


An integrative pan-cancer analysis illustrating the key role of LRP11 in cervical cancer.
Low density lipoprotein receptor-related protein 11 (LRP11) was involved in the progression of several tumors. However, its role in cervical cancer still remains uncertain. The original tumor data was downloaded from the Cancer Genome Atlas and genotype-tissue expression databases. The expression of LRP11 in normal tissues, tumor tissues and adjacent tissues were evaluated. In addition, we also explored the genetic alteration, prognostic value, and gene function of LRP11. We deeply assessed the interaction between LRP11 and tumor immunity at the pan-cancer level. Finally, research on the association between LRP11 and the resistance of anti-tumor drugs was carried out. LRP11 was highly expressed and played a risk prognostic factor in cervical cancer and a variety of tumors. Enrichment analysis revealed that LRP11 was involved in multiple tumor malignant pathways. Our research also pointed out the unique role between LRP11 and tumor immune microenvironment. The tumor immune microenvironment of patients with high expression of LRP11 are lack of most immune cells, indicating a immune desert tumor microenvironment. The final drug resistant analysis suggested that patients with high expression of LRP11 may be related to the resistance of many anti-tumor drugs. LRP11 was a potential oncogene and prognostic marker in cervical cancer and pan-cancer. Patients with high LRP11 expression may have immune desert tumor microenvironment.


Antibiotic Resistance and Biofilm Production Capacity in Clostridioides difficile.
Clostridioides difficile (C. difficile) is one of the primary pathogens responsible for infectious diarrhea. Antibiotic treatment failure, occurring in about 30% of patients, and elevated rates of antibiotic resistance pose a major challenge for therapy. Reinfection often occurs by isolates that produce biofilm, a protective barrier impermeable to antibiotics. We explored the association between antibiotic resistance (in planktonic form) and biofilm-production in 123 C. difficile clinical isolates. Overall, 66 (53.6%) out of 123 isolates produced a biofilm, with most of them being either a strong (44%) or moderate (34.8%) biofilm producers. When compared to susceptible isolates, a statistically higher percentage of isolates with reduced susceptibility to metronidazole or vancomycin were biofilm producers (p < 0.0001, for both antibiotics). Biofilm production intensity was higher among tolerant isolates; 53.1% of the metronidazole-susceptible isolates were not able to produce biofilms, and only 12.5% were strong biofilm-producers. In contrast, 63% of the isolates with reduced susceptibility had a strong biofilm-production capability, while 22.2% were non-producers. Among the vancomycin-susceptible isolates, 51% were unable to produce biofilms, while all the isolates with reduced vancomycin susceptibility were biofilm-producers. Additionally, strong biofilm production capacity was more common among the isolates with reduced vancomycin susceptibility, compared to susceptible isolates (72.7% vs. 18.8%, respectively). The distribution of biofilm capacity groups was statistically different between different Sequence-types (ST) strains (p =0.001). For example, while most of ST2 (66.7%), ST13 (60%), ST42 (80%) isolates were non-producers, most (75%) ST6 isolates were moderate producers and most of ST104 (57.1%) were strong producers. Our results suggest an association between reduced antibiotic susceptibility and biofilm production capacity. This finding reinforces the importance of antibiotic susceptibility testing, mainly in recurrence infections that may be induced by a strain that is both antibiotic tolerant and biofilm producer. Better adjustment of treatment in such cases may reduce recurrences rates and complications. The link of biofilm production and ST should be further validated; if ST can indicate on isolate virulence, then in the future, when strain typing methods will be more available to laboratories, ST determination may aid in indecision between supportive vs. aggressive treatment.


Adaptation of mRNA structure to control protein folding.
Comparison of mRNA and protein structures shows that highly structured mRNAs typically encode compact protein domains suggesting that mRNA structure controls protein folding. This function is apparently performed by distinct structural elements in the mRNA, which implies 'fine tuning' of mRNA structure under selection for optimal protein folding. We find that, during evolution, changes in the mRNA folding energy follow amino acid replacements, reinforcing the notion of an intimate connection between the structures of a mRNA and the protein it encodes, and the double encoding of protein sequence and folding in the mRNA.


First-principles study of the electronic structures of icosahedral TiN (N=13,19,43,55) clusters.
We have studied the electronic structures of icosahedral Ti(N) clusters (N=13, 19, 43, and 55) by using a real-space first-principles cluster method with generalized gradient approximation for exchange-correlation potential. The hexagonal close-packed and fcc close-packed clusters have been studied additionally for comparisons. It is found that the icosahedral structures are the most stable ones except for Ti(43), where fcc close-packed structure is favorable in energy. We present and discuss the variation of bond length, the features of the highest occupied molecular orbitals and the lowest unoccupied molecular orbital, the evolution of density of states, and the magnetic moment in detail. The results are in good agreement with the predictions from the collision-induced dissociation and size-selected anion photoelectron spectroscopy experiments.


Effects of farnesoid-X-receptor SUMOylation mutation on myocardial ischemia/reperfusion injury in mice.
Myocardial ischemia/reperfusion (MI/R) injury induces excessive cellular apoptosis and contributes significantly to final infarct size. We previously demonstrated that a nuclear receptor, Farnesoid X receptor (FXR), plays a crucial role in mediating myocardial apoptosis. The FXR functions are regulated by post translational modifications (PTM). However, whether the proapoptotic effect of FXR in MI/R injury is regulated by PTM remains unclear. Here, we aimed to study the effect of SUMOylation, a PTM involved in the pathogenesis of MI/R injury per se, on the proapoptotic effect of FXR in MI/R injury. We observed that FXR could be SUMOylated in heart tissues, and FXR SUMOylation levels were downregulated in ischemia reperfused myocardium. By overexpression of SUMOylation-defective FXR mutant, it was demonstrated that decreased SUMOylation augmented the detrimental effect of FXR, via activation of mitochondrial apoptosis pathway and autophagy dysfunction in MI/R injury. Further mechanistic studies suggested that decreased SUMOylation levels increased the transcription activity of FXR, and the subsequently upregulated FXR target gene SHP mediated the proapoptotic effects of FXR. Taken together, we provided the first evidence that the cardiac effects of FXR could be regulated by SUMOylation, and that manipulating FXR SUMOylation levels may hold therapeutic promise for constraining MI/R injury.


[Coronary Heart Disease at the Patient With Metabolic Syndrome: Strategy of Antianginal Therapy].
Fist-line drugs in ischemic heart disease are -adrenoblockers. However there are cases when comorbidities limit possibilities of their use. In metabolic syndrome some representatives of this class unfavorably affect insulin sensitivity, carbohydrate and lipid metabolism. Alternative is to use ivabradine - selective inhibitor of If receptors with negative chronotropic activity. Ivabradine is metabolically neutral, has no negative inotropic effect, no influence on atrioventricular conduction and arterial pressure.


Autoimmunity to ryanodine receptor and titin in myasthenia gravis is associated with GM allotypes.
Myasthenia gravis (MG) is mediated by autoantibodies against the acetylcholine receptor at the muscle endplate. Some MG patients have in addition antibodies (Ab) to the skeletal muscle proteins ryanodine receptor (RyR) and titin. We have examined GM and KM allotypes, RyR and titin Ab in 44 MG patients (37 thymoma patients and 7 non-thymoma, late-onset patients) and 292 non-MG controls to see if GM/KM allotypes associate with differences in autoantibody production. All patients had titin Ab, and 15 thymoma patients had also RyR Ab. The phenotype GM 1, 2, 3 23 5, 21 was significantly increased in the patients with titin Ab compared with the non-MG controls (chi2 = 4.93, p < 0.05). Thymoma patients with RyR Ab had a higher frequency of the GM 3 23 5 phenotype compared with RyR Ab negative patients and controls (chi2 = 7.1, p < 0.05). KM allotypes did not differ between RyR Ab positive or titin Ab positive patients and controls. GM phenotypes may thus be associated with an autoimmune response against the muscle proteins titin and RyR in MG patients.


Cuff bladder size in a blood pressure survey of children.
To investigate whether cuff bladder dimensions relative to the length and circumference of the upper arm affect the outcome of epidemiologic blood pressure surveys, multiple observers took multiple measurements on each of 92 grade school children from Franklinton and 351 children from Bogalusa, Louisiana. For the present study, the broad, hard surrounding cuff of the Physiometrics blood pressure recorder using a transducer embedded in the ample cuff bladder gave "true readings." Baumanometer readings were performed using standard cuff sizes selected according to currently recommended criteria. "Excess pressure reading" equal to mean Baumanometer reading minus mean true reading. "Deficient cuff bladder length" equal to percentage of upperarm circumference not covered by the rubber bladder. Pearson correlation coefficients for the two groups of children supported the hypothesis (at the 5% level of significance) that deficient cuff bladder length is associated with excess pressure reading. The relevant correlation coefficients for the two groups of children were 0.18 and 0.31 (systolic pressure) and 0.24 and 0.19 (diastolic pressure). In addition to sufficient cuff width, the complete surrounding of the entire arm circumference by the rubber bladder is recommended for epidemiologic studies of children.


The Do-It-Yourself Artificial Pancreas: A Comprehensive Review.
Diabetes technology (DT) has accomplished tremendous progress in the past decades, aiming to convert these technologies as viable treatment options for the benefit of patients with diabetes (PWD). Despite the advances, PWD face multiple challenges with the efficient management of type 1 diabetes. Most of the promising and innovative technological developments are not accessible to a larger proportion of PWD. The slow pace of development and commercialization, overpricing, and lack of peer support are few such factors leading to inequitable access to the innovations in DT. Highly motivated and tech-savvy members of the diabetes community have therefore come up with the #WeAreNotWaiting movement and started developing their own do-it-yourself artificial pancreas systems (DIYAPS) integrating continuous glucose monitoring (CGM), insulin pumps, and smartphone technology to run openly shared algorithms to achieve appreciable glycemic control and quality of life (QoL). These systems use tailor-made interventions to achieve automated insulin delivery (AID) and are not commercialized or regulated. Online social network megatrends such as GitHub, CGM in the Cloud, and Twitter have been providing platforms to share these open source technologies and user experiences. Observational studies, anecdotal evidence, and real-world patient stories revealed significant improvements in time in range (TIR), time in hypoglycemia (TIHypo), HbA1c levels, and QoL after the initiation of DIYAPS. But this unregulated do-it-yourself (DIY) approach is perceived with great circumspection by healthcare professionals (HCP), regulatory bodies, and device manufacturers, making users the ultimate risk-bearers. The use of the regularized CGM and insulin pump with unauthorized algorithms makes them off-label and has been a matter of great concern. Besides these, lack of safety data, funding or insurance coverage, ethical, and legal issues are roadblocks to the unanimous acceptance of these systems among patients with type 1 diabetes (T1D). A multi-agency approach is necessary to evaluate the risks, and to delineate the incumbency and liability of clinicians, regulatory bodies, and manufacturers associated with the use of DIYAPS. Understanding the potential of DIYAPS as the need of the present time, many regional and international agencies have come with strategies to appraise its safety as well as to support education and training on its use. Here we provide a comprehensive description of the DIYAPS-including their origin, existing literature, advantages, and disadvantages that can help the industry leaders, clinicians, and PWD to make the best use of these systems.


Conditions for religious discourse in secularized ethical health care deliberation.
Religious discourse is no longer self-evident in professional health care ethical deliberation in the North Atlantic cultural sphere. However, in a world of pluralism, care professionals still seek substantive views of good care. Religious and non-religious beliefs should not be excluded from ethical deliberation. They offer patients and professionals a helpful language for expressing values and beliefs. Chaplains have a role to play as allies in sense-making processes and resourcing care.


Reconstructing human pancreatic differentiation by mapping specific cell populations during development.
Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.


Fluorescent RNA cytosine analogue - an internal probe for detailed structure and dynamics investigations.
The bright fluorescent cytosine analogue tCO stands out among fluorescent bases due to its virtually unquenched fluorescence emission in duplex DNA. However, like most reported base analogues, it has not been thoroughly characterized in RNA. We here report on the first synthesis and RNA-incorporation of tCO, and characterize its base-mimicking and fluorescence properties in RNA. As in DNA, we find a high quantum yield inside RNA duplexes (<ΦF> = 0.22) that is virtually unaffected by the neighbouring bases (ΦF = 0.20-0.25), resulting in an average brightness of 1900 M-1 cm-1. The average fluorescence lifetime in RNA duplexes is 4.3 ns and generally two lifetimes are required to fit the exponential decays. Fluorescence properties in ssRNA are defined by a small increase in average quantum yield (<ΦF > = 0.24) compared to dsRNA, with a broader distribution (ΦF = 0.17-0.34) and slightly shorter average lifetimes. Using circular dichroism, we find that the tCO-modified RNA duplexes form regular A-form helices and in UV-melting experiments the stability of the duplexes is only slightly higher than that of the corresponding natural RNA (<ΔT m> = + 2.3 °C). These properties make tCO a highly interesting fluorescent RNA base analogue for detailed FRET-based structural measurements, as a bright internal label in microscopy, and for fluorescence anisotropy measurements of RNA dynamics.


Posterior mitral leaflet repair with a simple segmental annulus support: the 'double-Teflon technique'.
The study aim was to present immediate and late results of a modified technique for mitral valve repair--the 'double-Teflon technique'. This consists of quadrangular resection of the posterior leaflet, annulus plication with 'pledgetted' stitches over a Teflon patch, and leaflet suture. Seventy-two patients (41 males, 31 females; mean age 60.5+/-11.9 years) with mitral insufficiency due to myxomatous degeneration and ruptured or elongated chordae tendineae underwent mitral valve repair with this technique. Fifteen patients (18%) had associated cardiovascular disease including coronary artery disease, aortic insufficiency, aortic stenosis and atrial septal defect. Operative, immediate postoperative and late operative echocardiographic data of the first 29 patients were analyzed. Actuarial survival was assessed using the Kaplan-Meier method. There was one operative death (1%). By the late postoperative period, 95% of survivors were in NYHA functional class I. There were no episodes of hemolysis or endocarditis; the linearized rate for thromboembolism was 1.4%/patient-year. Actuarial survival at 72 months was 94.5+/-3.2%. Doppler echocardiography showed a significant decrease in mean left atrial diameter (p = 0.0001) and left ventricular diastolic diameter (p = 0.0003). Mitral valve repair with the 'double-Teflon technique' is associated with low operative mortality, satisfactory survival rates, and good clinical outcome.


Binding of bacteriocin Clo DF13 to Clo DF13 plasmid deoxyribonucleic acid in vivo and in vitro.
The bacteriocinogenic plasmid Clo DF13 is present in Escherichia coli to the extent of 10 copies per cell. A complex of Clo DF13 plasmid deoxyribonucleic acid (DNA) and protein can be isolated from cells. Treatment of the complex with ionic detergents or proteases dissociates the complex but does not convert any supercoiled Clo DF13 DNA to the open circular form, indicating that this complex is not a relaxation complex. The complex is stable in 0.5 M NaCl and contains one polypeptide species. The protein, present in the complex, appeared to be bacteriocin Clo DF13 for the following reasons: (i) the protein is de novo synthesized in Clo DF13-harboring minicells, indicating that this protein is Clo DF13 specific; (ii) this protein shows bacteriocinogenic activity on a bacteriocin Clo DF13-susceptible indicator strain; (iii) this protein has the same molecular weight (60,000) as bacteriocin Clo DF13. DNA-protein binding experiments, involving QAE-Sephadex column chromatography and nitrocellulose membrane filters, demonstrate that bacteriocin Clo DF13 has also affinity in vitro for Clo DF13 DNA. Membrane filter binding experiments revealed that bacteriocin Clo DF13 does not interact with other DNA species, such as ColE1 DNA, yeast DNA, calf thymus DNA, phiX174 DNA, and also not with denatured Clo DF13 DNA. In addition no binding to Clo DF13 DNA of a related bacteriocin, colicin E3, could be detected. These results indicate that the binding of bacteriocin Clo DF 13 to double-stranded Clo DF13 DNA is very specific.


Background air concentrations of Cr(VI) in Hudson County, New Jersey: implications for setting health-based standards for Cr(VI) in soil.
An accurate measure of "background" airborne Cr(VI) concentrations will be necessary to derive site-specific health-based Cr(VI) soil concentrations at sites containing chromite ore processing residues (COPR) in Hudson County, NJ. To date, no such data have been collected in New Jersey. This paper describes an air sampling program designed to measure background concentrations of Cr(VI) in Hudson County and compare those concentrations with the air sampling results obtained previously at 30 COPR sites in Hudson County. Background airborne Cr(VI) concentrations ranged from 0.2 to 3.8 ng/m3 with an arithmetic mean of 1.2 ng/m3. Comparisons of the airborne Cr(VI) concentrations previously measured at 30 COPR sites indicated that more than two-thirds of the sites had mean airborne Cr(VI) concentrations that were not statistically significantly greater than background. Our findings suggest that, in general, vehicle disturbance is required for significant soil suspension to occur at these sites. Since airborne Cr(VI) concentrations at many of these sites are close to background, it is critical that background airborne Cr(VI) levels be considered when deriving health-based soil standards at the COPR sites.


Significance of CD133 expression in esophageal squamous cell carcinoma.
CD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers. We studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR). Pathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018). This study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.


Identification of functional receptors for ciliary neurotrophic factor on chick ciliary ganglion neurons.
Ciliary neurotrophic factor and an avian homolog, growth promoting activity, are members of the cytokine/neurokine family of trophic factors and have been proposed to function as survival and developmental factors for ciliary ganglion neurons in vivo. Here we identify for the first time functional receptors for ciliary neurotrophic factor and growth promoting activity on cultured ciliary ganglion neurons. [(125)I]Rat ciliary neurotrophic factor binding studies indicate that rat ciliary neurotrophic factor and growth promoting activity bind to these receptors with a single affinity, while human ciliary neurotrophic factor recognizes both a high- and low-affinity site. Comparison of the relative potency of human ciliary neurotrophic factor and avian growth promoting activity in biological assays indicates that growth promoting activity is three to five times more active in promoting survival and in regulating acetylcholine receptors. The binding of ciliary neurotrophic factor is specific, sensitive to phosphatidylinositol-specific phospholipase C and partially inhibited by leukemia inhibitory factor, but not inhibited by other members of the human neurokine family, including interleukin-6, interleukin-22 and oncostatin M. Cross-linking of [(125)I]rat ciliary neurotrophic factor to ciliary neurons results in the specific labeling of three proteins with estimated molecular masses of 153,000, 81,000 and 72,000. Only the 81,000 molecular weight component is released from the cells after treatment with phosphatidylinositol-specific phospholipase C, suggesting a membrane attachment via a glycosylphosphatidylinositol linkage. Stimulation with ciliary neurotrophic factor or growth promoting activity, but not by other neurokines, results in the rapid tyrosine phosphorylation of a 90,000 molecular weight protein that is inhibited by pretreatment with phosphatidylinositol-specific phospholipase C. In conclusion, we report here the pharmacological and functional properties of ciliary neurotrophic factor receptors on embryonic ciliary ganglion neurons. These results provide the means for elaborating the molecular mechanisms of ciliary neurotrophic factor action and understanding its physiological role in a defined neuronal population.


Newly isolated microorganisms with potential application in biotechnology.
Nowadays, food, cosmetic, environmental and pharmaceutical fields are searching for alternative processes to obtain their major products in a more sustainable way. This fact is related to the increasing demand from the consumer market for natural products to substitute synthetic additives. Industrial biotechnology appears as a promising area for this purpose; however, the success of its application is highly dependent of the availability of a suitable microorganism. To overcome this drawback, the isolation of microorganisms from diverse sources, including fermented food, adverse environments, contaminated samples or agro-industrial wastes is an important approach that can provide a more adaptable strain able to be used as biocatalyst and that exhibit resistance to industrial conditions and high yields/productivities in biotechnological production of natural compounds. The aim of this review is to provide a solid set of information on the state of the art of isolation and screening studies for obtaining novel biocatalysts able to produce natural compounds, focusing in aromas, biosurfactants, polysaccharides and microbial oils.


MDG‑1 inhibits H2O2‑induced apoptosis and inflammation in human umbilical vein endothelial cells.
MDG‑1, a water‑soluble polysaccharide extracted from Ophiopogon japonicus, has been reported to serve a role in antimyocardial ischemia by protecting cardiomyocytes from hypoxia/reoxygenation‑induced damage. However, it remains unknown whether MDG‑1 protects human umbilical vein endothelial cells (HUVECs) against oxidative stress‑induced damage. In the present study, HUVECs were treated with hydrogen peroxide (H2O2) to establish an oxidative stress‑induced cell injury model. Treatment of HUVECs with different concentrations of H2O2 significantly attenuated cell viability and increased cell apoptosis in a time and dose‑dependent manner. Pretreatment with MDG‑1 markedly reduced H2O2‑induced cell death, ROS generation and inflammatory factor secretion. In addition, pretreatment with MDG‑1 decreased the expression levels of proapoptotic proteins BCL2 associated X (Bax) and caspase‑3, while it increased the expression levels of the antiapoptotic protein BCL2 apoptosis regulator (Bcl‑2), compared with H2O2 treatment alone. Taken together, the present data suggest that MDG‑1 protected HUVECs against H2O2‑induced apoptosis and inflammation through inhibition of Bax/Bcl‑2 protein ratio, caspase‑3 expression, and inflammatory factor secretion. This study provides a potential application for MDG‑1 in the treatment of cardiovascular disease.


Admission proforma significantly improves the medical record.
The authors worked in a busy regional fracture unit, where it was noted that important data was being omitted from medical notes. In an attempt to improve on this, an admission proforma was formulated. This was designed to be easily and quickly completed. Notes were audited on two separate weeks, the first before, and the second after introduction of the proforma. The overall results demonstrate statistically significant improvements in documentation with a proforma, and concur with the limited previous literature in this area.


Nitroglycerin tolerance in vitro: effect on cGMP turnover in vascular smooth muscle.
Bovine mesenteric arteries (BMA) were made tolerant to nitroglycerin (GTN) by incubation with high concentrations of GTN at elevated pH. This treatment has previously been shown to reduce the relaxant and cGMP-elevating action of a challenging dose of GTN. The stimulatory action of nitroprusside (NP) or GTN/cysteine on guanylate cyclase (GC) was reduced by 50-60% in GTN-tolerant vessels as compared to control vessels. The stimulatory action of GTN and NP on GC has been suggested to occur through formation of S-nitrosothiols, probably with a previous denitration step required for GTN. However, tolerance induction to GTN was not found to change the rate of nitrite formation from GTN, and exogenous addition of thiols in the GC assay, in order to increase S-nitrosothiol formation, did not restore the GC activity in tolerant vessels back to control level. This is suggested to indicate a direct effect of GTN tolerance on GC. Since the cGMP-phosphodiesterase activity was not affected in GTN-tolerant vessels, the reduced GC activity may be of a crucial importance for the reduced cGMP response in GTN-tolerant BMA as found earlier (Axelsson et al. 1982).


Temperature-dependent growth of germanium oxide and silicon oxide based nanostructures, aligned silicon oxide nanowire assemblies, and silicon oxide microtubes.
We demonstrate the temperature-dependent growth of germanium oxide and silicon oxide based composite nanostructures (multiple nanojunctions of Ge nanowires and SiO(x) nanowires, Ge-filled SiO(2) nanotubes, Ge/SiO(2) coaxial nanocables, and a variety of interesting micrometer-sized structures), aligned SiO(x) nanowire assemblies, and SiO(x) microtubes. The structures were characterized by SEM, TEM, energy-dispersive X-ray spectroscopy, and electron diffraction. The combination of laser ablation of a germanium target and thermal evaoporation of silicon monoxide powders resulted in the formation of Ge and SiO(x) species in a carrier gas; the nano/micro-sized structures grow by either a Ge-catalyzed vapor-liquid-solid or a Ge-nanowire-templated vapor-solid process.


Is field (vagal) stimulation of gastric acid secretion mediated by M1 or non-M1 muscarinic receptors? A methodical problem exemplified in the mouse stomach in vitro.
1. Highly controversial claims have been put forward in the literature as to the involvement of either M1 or non-M1 muscarinic receptors in the field (vagal) stimulation of gastric acid secretion. This mini-review considers three available sets of data obtained in the mouse isolated, lumen-perfused stomach. 2. While pA2 values seemed to favour non-M1 receptors, a comparison between M1 selective versus non-selective antagonists on the one hand and field stimulation versus bethanechol stimulation on the other clearly pointed to M1 receptors being involved. 3. In the present review we discuss a novel experimental approach supporting the latter concept of M1 receptors. This novel approach provides a simple though provocative way to deal with the particular difficulties in determining pA2 values in the acid-secreting gastric mucosa. It is based on the rank order in the effects of different antagonists relative to their receptor type-dependent affinities, when employed at a fixed concentration, rather than on their pA2 values.


Early adversity and adult health outcomes.
Adversity in childhood has effects on mental and physical health, not only in childhood but across the lifespan. A chief task of our research has been to define the pathways by which childhood experience has these surprising health outcomes, often decades later. The concept of allostatic load, which refers to dysregulations across major biological regulatory systems that have cumulative interacting adverse effects over time, provides a mechanism for understanding these relations and defining specific pathways. To chart these pathways, we examine early childhood socioeconomic status, family environment, and genetic predispositions as antecedents to socioemotional functioning/psychological distress; and neural responses to threat that have downstream effects on major stress regulatory systems, ultimately culminating in risks to mental and physical health outcomes. This integrative approach to investigating the impact of childhood experience on adult health outcomes illustrates the significance of multilevel integrative approaches to understanding developmental psychopathology more generally.


Perpetually Positive: Post-COVID Interstitial Lung Disease in an Immunocompromised Patient With Diffuse Large B-cell Lymphoma.
As more patients recover from COVID-19 infection, long-term complications are beginning to arise. Our case report will explore a debilitating long-term complication, Post-COVID Interstitial Lung Disease (PC-ILD). We will introduce a patient who developed PC-ILD in the setting of diffuse large B-cell lymphoma, outlining a difficult hospital course, including a positive COVID-19 polymerase chain reaction (PCR) for more than 3 months. We will then discuss the human body's physiological response to the virus and how our patient was not able to adequately mount an immune response. Finally, the pathophysiology of PC-ILD will be explored and correlated with the patient's subsequent computed tomographic images obtained over a 3-month period. The difficult hospital course and complex medical decision-making outlined in this case report serve as a reminder for health care providers to maintain vigilance in protecting our most vulnerable patient population from such a devastating disease process.


A scoping review of adult chronic kidney disease clinical pathways for primary care.
Chronic kidney disease (CKD) affects ∼10% of the adult population. The majority of patients with CKD are managed by primary care physicians, and despite the availability of effective treatment options, the use of evidence-based interventions for CKD in this setting remains suboptimal. Clinical pathways have been identified as effective tools to guide primary care physicians in providing evidence-based care. We aimed to describe the availability, characteristics and credibility of clinical pathways for adult CKD using a scoping review methodology. We searched Medline, Embase, CINAHL and targeted Internet sites from inception to 31 October 2014 to identify studies and resources that identified adult CKD clinical pathways for primary care settings. Study selection and data extraction were independently performed by two reviewers. From 487 citations, 41 items were eligible for review: 7 published articles and 34 grey literature resources published between 2001 and 2014. Of the 41 clinical pathways, 32, 24 and 22% were from the UK, USA and Canada, respectively. The majority (66%, n = 31) of clinical pathways were static in nature (did not have an online interactive feature). The majority (76%) of articles/resources reported using one or more clinical practice guidelines as a resource to guide the clinical pathway content. Few articles described a dissemination and evaluation plan for the clinical pathway, but most reported the targeted end-users. Our scoping review synthesized available literature on CKD clinical pathways in the primary care setting. We found that existing clinical pathways are diverse in their design, content and implementation. These results can be used by researchers developing or testing new or existing clinical pathways and by practitioners and health system stakeholders who aim to implement CKD clinical pathways in clinical practice.


Equivalence of glass transition and colloidal glass transition in the hard-sphere limit.
We show that the slowing of the dynamics in simulations of several model glass-forming liquids is equivalent to the hard-sphere glass transition in the low-pressure limit. In this limit, we find universal behavior of the relaxation time by collapsing molecular-dynamics data for all systems studied onto a single curve as a function of T/p, the ratio of the temperature to the pressure. At higher pressures, there are deviations from this universal behavior that depend on the interparticle potential, implying that additional physical processes must enter into the dynamics of glass formation.


Picture-digit differences in processing clock times.
Clock times displayed as digits and as clockfaces were used as stimuli in a series of experiments that tested the hypothesis that a common numerical code was used for processing clock times. Whether the task involved reading times or making comparative judgments of early/late or same/different, digits were always processed faster than clockfaces . The size of the format effect varied, however, with the processing demands of the task and with times at specific locations on the clockface . Also, automatic processing of times presented as clockfaces interfered with comparative judgments made with digits, but digital distractors were not found to interfere with judgments made to times as clockfaces . The findings are discussed within the context of picture-word differences in rate of access to articulatory and semantic codes. Conclusions are also made regarding the relative efficiency of displaying times digitally and in the form of clockfaces .


Surgical Treatment of a Giant Right Hepatic Artery Aneurysm with an Aberrant Left Hepatic Artery: Report of a Case.
Hepatic artery aneurysms are rare. We describe a case of a successful surgical treatment of a giant hepatic aneurysm without revascularization. A 63-year-old female was admitted to our department complaining of abdominal pain. Computed tomography showed a thrombosed hepatic artery aneurysm measuring 5.5 cm in diameter. A celiac angiography revealed an aberrant left hepatic artery and a right hepatic aneurysm. Liver blood flow and the right hepatic aneurysm were visualized via collateral pathway from the aberrant left hepatic artery. We performed an aneurysmorrhaphy without revascularization. Postoperative course was uneventful and the patient is doing well 3 months after surgery.


Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators.
Although androgen receptor (AR)-mediated signaling is central to prostate cancer, the ability to modulate AR signaling states is limited. Here we establish a chemical genomic approach for discovery and target prediction of modulators of cancer phenotypes, as exemplified by AR signaling. We first identify AR activation inhibitors, including a group of structurally related compounds comprising celastrol, gedunin, and derivatives. To develop an in silico approach for target pathway identification, we apply a gene expression-based analysis that classifies HSP90 inhibitors as having similar activity to celastrol and gedunin. Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy.


Desiccation and ethanol resistances of multidrug resistant Acinetobacter baumannii embedded in biofilm: The favorable antiseptic efficacy of combination chlorhexidine gluconate and ethanol.
Globally, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as an important pathogen in nosocomial outbreaks. This study aimed to investigate the correlation between the biofilm formation and survival of MDRABs, and to investigate the antiseptic efficacy of hand sanitizers for the MDRABs, embedded with biofilm (MDRAB-Bs). The MDRABs were selected randomly after pulsed-field gel electrophoresis (PFGE), and their biofilm formation was analyzed. Desiccation and ethanol tolerances were assayed to test the bacterial survival. The antiseptic efficacy of combined chlorhexidine gluconate (CHG) and 70% ethanol agents against MDRAB-Bs were compared with the 70% ethanol cleanser. Eleven MDRABs, which varied in biofilm formation (MRDAB-B) and planktonic type (MDRAB-P), were tested. In desiccation survival, the mean survival time for the MDRAB-Bs was 49.0 days which was significantly higher than that of their planktonic type (17.3 days) (P < 0.005). The MDRAB-Ps could be eliminated after a 10 min contact with a 30% ethanol agent, however, it took 10 min of 70% ethanol to eliminate the MDRAB-Bs. On the other hand, a 2% CHG in 70% ethanol solution completely eliminated all MDRAB-Bs after 1 min contacted time. The 2% CHG in 70% ethanol agent provided a significantly superior efficacy than the 70% ethanol solution at eliminating the MDRAB-Bs (P < 0.005). MDRAB with biofilm-formation presented significantly higher desiccation and ethanol resistances than their planktonic type. Moreover, the 2% CHG in 70% ethanol agent provided a superior antiseptic efficacy for MDRAB-Bs than that of the 70% ethanol agent.


Autocrine extracellular signal-regulated kinase (ERK) activation in normal human keratinocytes: metalloproteinase-mediated release of amphiregulin triggers signaling from ErbB1 to ERK.
ErbB signaling through extracellular signal-regulated kinase (ERK) has been implicated in regulating the expression of ErbB ligands in hyperproliferative skin disorders and wound healing. Here, we characterize the process of autocrine ERK activation in cultured normal human keratinocytes (NHKs) subjected to growth factor (GF) deprivation. Basal ERK phosphorylation was lower after 48 h than after 24 h of GF deprivation, and lowest at 30-60 min after an additional medium change. ERK phosphorylation was markedly increased by low concentrations of epidermal growth factor (EGF) (0.2-1 ng/ml) that provoked only a limited increase in ErbB1 tyrosine phosphorylation and internalization. Basal ErbB tyrosine phosphorylation and ERK phosphorylation were inhibited by two different ErbB receptor tyrosine kinase inhibitors, by the ErbB1-specific neutralizing monoclonal antibody 225 IgG, by two different metalloproteinase inhibitors, and by neutralizing antibodies against amphiregulin (AR). In contrast, these responses were unaffected by neutralizing antibodies against other ErbB1 ligands or the ErbB2 inhibitors geldanamycin and AG825. The time course of autocrine ERK phosphorylation correlated with the appearance of soluble AR, and two different metalloproteinase inhibitors blocked AR release. These results define an amphiregulin- and ErbB1-dependent mechanism by which autocrine ERK activation is maintained in NHKs, even when ErbB1 autophosphorylation and internalization are limited.


Urinary diversion: 30 years experience of a single centre in Republic of Macedonia.
The aim of this report is to present our 30 years experience with various types of urinary diversions, in particular the Bricker and Studer techniques for the management of muscle invasive bladder cancer at our institution. Perioperative, early and late complications are also evaluated. Between 1977 and 2007, 186 male and 15 female patients underwent combined radical cystectomy, pelvic lymphadenectomy and urinary diversion. In two subgroups of patients we evaluated the complications, divided as early and late, and subdivided as those related or unrelated to the neobladder. Mean follow up time was 28 months (range 12-60 months). Two main types of urinary diversion were performed: the ileal conduit diversion using a technique previously described by Bricker and the ileal neobladder diversion using a technique previously described by a Studer. The ages at surgery ranged from 40 to 82 years with a mean age of 60 years. Histopathologically, transitional cell carcinoma was the most common tumor cell type (93,7%), followed by difuse papilomatosis (5.5%) and adenocarcinoma (0.7%). The pathological tumor stage was pT1 (4.7%), pT2 (31.4%), pT3 (50.3 %) and pT4a (13,3%). Histological evidence of regional lymph node involvement was seen in 25% of the cases. From 52 patients from the Studer subgroup perioperative complications were found in 16 patients (30.7%). Specific early complications directly related to the neobladder occurred in 14 (26.9%) patients. Prolonged ileus in 2 patient (3.8%), ureteral leakage in 9 patients (17.3%), mucous buildup within the diversion in 3 patients (5.7%). Late complications occurred in 10 patients (19.2%): retention of the urine in 4 patients (7.6%) (stricture of the urethra-pouch anastomosis in one 1 patient) and to big reservoir in 3 patients. One patient (1.9%) developed prolonged metabolic acidosis. Stone formation was observed in one patient, two years postoperatively. Unilateral hydroureteronephrosis was observed in 2 patients whereas bilateral hydroureteronephrosis was observed in one patients at one year postoperatively. Perioperative and late complications were similar in the 32 patients from the Bricker subgroup. We show that our results with urinary diversion are promising in patients requiring radical cystoprostatectomy. The two methods preferred in our institution offer a sufficient protection of the upper urinary tract with a low complication rate, good voiding function and continence.


Complex pattern of colon cancer recurrence including a kidney metastasis: a case report.
We report a case of a 77-year-old female with a local recurrence of cancer after right hemicolectomy which infiltrated the pancreatic head affording pancreatoduodenectomy, who developed 3 years later recurrent tumor masses localized in the mesentery of the jejunum and in the lower pole of the left kidney. Partial nephrectomy and a segment resection of the small bowel were performed. Histological examination of both specimens revealed a necrotic metastasis of the primary carcinoma of the colon. Although intraluminal implantation of colon cancer cells in the renal pelvic mucosa from ureteric metastasis has been described, metastasis of a colorectal cancer in the kidney parenchyma is extremely rare and can be treated in an organ preserving manner. A complex pattern of colon cancer recurrence with unusual and rare sites of metastasis is reported.


Rapid progression of acquired amegakaryocytic thrombocytopenia to myelodysplastic syndrome: case report.
Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disease characterized by severe thrombocytopenia due to selective reduction or absence of megakaryocytes in the bone marrow. More commonly, patients with AAT have additional hematologic abnormalities such as macrocytosis or dyserythropoiesis, abnormalities which may predict progression to aplastic anemia or myelodysplasia. A 52-year-old female was admitted to hospital with mucosal and gingival bleeding. Megakaryocytes were not seen on the bone marrow aspiration and biopsy. AAT was diagnosed. Although she was treated with immunosuppressive therapy including prednisolone and cyclosporine, her disease progressed to myelodysplastic syndrome. She died at the third month of diagnosis because of cerebral bleeding.


Distribution of heavy metals around the Barakah nuclear power plant in the United Arab Emirates.
Inductively coupled plasma emission spectroscopy was used to measure the concentrations of heavy metals in 58 samples collected from the Barakah nuclear power plant (BNPP) area, UAE. The grain size distribution was symmetric, but the samples ranged from fine to coarse sand. The inverse relationship between grain size and heavy metal contaminations was validated. The pre-operational average heavy metal contaminations around the BNPP were 0.03, 0.40, 1.2, 2.05, 1.66, 1.6, 5.9, 7.3, 7, 8.8, 60, and 2521 ppm for Cd, Mo, Co, Cu, Pb, As, Zn, Ni, V, Cr, Mn, and Fe, respectively. The spatial distribution was more compact in the south compared to the north, with less severe contaminations in the east and west. The negative geoaccumulation indices suggest an uncontaminated area, and the BNPP has minor enrichments. All concentrations were significantly below the safe limits set by the Dutch guidelines. The levels of heavy metals reported in the UAE were lower than levels reported in countries around the world.


Quantitative and qualitative study of the restoration by cytokines of mononuclear cell delivery to skin test sites in anergic surgical patients.
We tested the hypothesis that anergy is associated with reduced delivery of mononuclear cells (MNCs) to delayed-type hypersensitivity sites and that cytokine (CK)-rich supernatants from mixed lymphocyte cultures overcome the defect. Significantly fewer MNCs were delivered to skin window chambers placed over purified protein derivative (PPD) injection sites of previously sensitized anergic patients compared with hospitalized PPD-reactive patients; coinjection of CK with PPD restored the MNC delivery in anergic patients to normal levels. The T cells cloned from a PPD + CK site of an anergic patient consisted of CD4+ and CD8+ cells whose capacities included cytotoxicity and lymphokine production. The frequency of PPD-reactive cells was 15 times greater than in the blood. Thus, the restoration by CK of the delivery of antigen-specific cells capable of participating in cell-mediated immunity in anergic patients may be feasible.


Endoscopic surgery in orthopaedics.
Arthroscopy and operative arthroscopy of the knee joint is today the most common orthopaedic procedure. However, some fifteen years ago it was almost unknown and used only by a small group of enthusiasts. With progress in the development of arthroscopic equipment, it is possible to examine all of the major joints, such as the wrist, ankle, elbow and shoulder, and therapeutic procedures can be undertaken to correct pathological findings in all of these joints. The advantages of endoscopic joint surgery are indisputable, with short rehabilitation periods, precise surgery, short hospital stays and lower costs mentioned being of primary importance. The technique, however, is difficult to learn and should be taught individually and step by step by experienced endoscopists. With the development of refined technology and better endoscopic equipment the need for open arthrotomy in the treatment of joint disorders has virtually been eliminated.


[Conservative and functional management for soft tissue sarcomas of the extremities: role of radiotherapy].
Recent publications have permitted to quantify the benefit of radiotherapy in the conservative treatment of soft tissue sarcoma of the limbs. The aim of this review is to focus on aspects of radiotherapy witch influence local control and functional outcome for early and late normal tissue damage. The evaluation of late effects is performed according to Soma-Lent (Subjective-Objective-Management-Analytic-Late Effects of Normal Tissues) classification. About complications, neurological complications are probably under estimated and are related to total dose of radiation therapy.


[Psychiatric complication of an implanted automatic defibrillator].
The implantable automatic defibrillator has completely changed the prognosis of potentially fatal ventricular arrhythmias by the delivery of an electric shock in the event of ventricular tachycardia or fibrillation. This vital device is sometimes poorly accepted from the psychological point of view by patients having been traumatised by experiences of sudden death from which they have been rescuscitated. Anxiety and depression are common and they have an important effect on the quality of life. The unpredictable occurrence of painful, multiple and uncontrollable electrical shocks may induce a state of acute stress with stunning, the resemblance of which to the model of learned helplessness described experimentally in the animal by Seligman, is discussed. The authors report the case of a 20 year old man whose automatic defibrillator was activated twenty times in one night. His state of stress and impotence was such that he lay prostate in his bed. Suicide seemed to be the only possible way of escaping from the electrical shocks of the device which was perceived as being dangerous. The management of this condition is not standardised but it requires the collaboration of the cardiac rhythmological and psychiatric teams. Medication with antidepressant drugs alone is not sufficient. The regulation of the sensitivity of the defibrillator gives the patient a feeling of mastering the situation: submission is not total! Research along this line should improve the patients' acceptation of the device and their quality of life.


Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling.
The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance. However, the molecular mechanisms underlying PCa chemoresistance remain unclear. The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance. Parental PC3 and DU145 cells and their chemoresistant PC3-TxR and DU145-TxR cells were analyzed. PC3-TxR and DU145-TxR cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin; PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin. Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction. Tumor cell migration, invasion, and colony formation were then evaluated by wound healing, transwell, and colony formation assays, respectively. The drug sensitivity was evaluated using MTS assay. Chemoresistant PC3-TxR and DU145-TxR cells exhibited an invasive and metastatic phenotype that associated with EMT, including the down-regulation of E-cadherin and up-regulation of Vimentin, Snail, and N-cadherin, comparing with that of parental PC3 and DU145 cells. When E-cadherin was overexpressed in PC3-TxR and DU145-TxR cells, the expression of Vimentin and Claudin-1 was down-regulated, and tumor cell migration and invasion were inhibited. In particular, the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-TxR and DU145-TxR cells. When E-cadherin expression was silenced in parental PC3 and DU145 cells, the expression of Vimentin and Snail was up-regulated, and, particularly, the sensitivity to paclitaxel was decreased. Interestingly, Notch-1 expression was up-regulated in PC3-TxR and DU145-TxR cells, whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells. The use of γ-secretase inhibitor, a Notch signaling pathway inhibitor, significantly increased the sensitivity of chemoresistant cells to paclitaxel. The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling, and inhibiting the Notch signaling pathway may reverse PCa chemoresistance.