[Laparoscopic sacrocolpopexy for pelvic organ prolapse: guidelines for clinical practice].
Open sacrocolpopexy have demonstrated its efficiency in surgical treatment of pelvic organ prolapse with an important backward on a large number of patients. Laparoscopic sacrocolpopexy reproduced the same surgical technique with reduced morbidity and may benefits from the recent development of robotic. Numerous technical variants have been developped around the original procedure but results seems not ever equivalent. Our objectives are to establish practical recommendations issues from the data of the litterature on the various technical aspects of this technique. This work leans on an exhaustive lecture of the literature concerning meta analyses, randomized tries, registers, controlled studies and the largest non controlled studies published on the subject. Recommendations were developed by a multidisciplinary workgroup then reread and amended by an also multidisciplinary group of proofreaders (urologists, gynecologists, gastroenterologists and surgeons). The methodology follows at best the recommendations of the HAS with a scientific argument for every question (accompanied with the level of proof, NP) and the recommendations, the officers (In, B, C and agreement of experts) and validated at the end of the phase of review. Surgical treatment of uro-genital prolapse by abdominal route classically associated hystero and anterior vaginopexy on the sacral ligament with a synthethic mesh. There are no argument to systematically associated a posterior vaginopexy to prevent secondary rectocele (level C). The consensual indication of laparoscopic rectopexy is represented by symptomatic rectal prolapse, the anatomical and functional results of which are the best estimated (level C). The surgical treatment of rectocele, elytrocele and enterocele with a posterior vaginopexy is not well estimated (level 3). Thus, it is not possible to conclude on the results of a posterior vaginal fixation with a mesh in these indications (AP). In the absence of colpocèle, the interest brought by the posterior vaginal mesh is not established (level 3). There is no comparative studies which allows to conclude on the type and mode of fixation of the prostheses of sacrocolpopexy. We would only report the most common practices without other conclusion. The anterior mesh is usually fixed upper on the anterior part of uterus cervix and lower on the anterior vaginal wall. These fixations are most of the time made by suture and on the promontory with non absorbable suture. The great majority of the authors recommend to make a peritonisation of prostheses to limit the risk of post-operative occlusion. It is now recommended to use only 2 kind of not absorbable prostheses: type I (macroporous polypropylene) or type III (polyester) and not to use any more prostheses type II (PTFE, Silicone) (level C) because of a high rate of mesh erosion: PTFE (9 %) or Silicone (19%) (level 3). Biological prostheses are no more recommended, because of short and medium-term lower anatomical results (level B). Anatomical and functional results are not stastistically differents between laparotomy and coelioscopy (NP1) but the comparison of tong-term results between both ways is not yet established. Coelioscopy allows significant reduction of blood losses, hospital stay and return to normal activity (level 1). Furthemore, there is a higher level of post-operative complications in laparotomy (level 1). When sacrocolpopexy is indicated, coelioscopy is thus recommended (level B). During coelioscopic sacrocolpopexy, anatomical and functional result have not shown any significance difference when using or no a robotics assistance but real randomised studies does not exist (level 2). In comparison to coelioscopy, robotic seems not to improve post-operative consequences and not to decrease the rate of complications of sacrocolpopexy (level 3). Robotic assistance cannot be yet recommended when a coelioscopic sacrocolpopexy is indicated (rank B). Sacrocolpopexy using not absorbable meshes allows to cure pelvic organ prolapses with very good results with few complications in terms of prothetic exposure and infection and thus is now considered as the referent prothetic surgical technique in this indication. Thus, it seems very important to establish clear recommendations on the numerous operating technical variants which developed around the original technique. © 2016 Published by Elsevier Masson SAS.


Bilateral symptomatic adrenal myelolipoma.
Adrenal myelolipomas are rare, nonfunctioning benign tumors that consist of mature fat and bone-marrow elements. In the first half of this century, most adrenal myelolipomas were found incidentally at autopsy. These tumors are usually unilateral and asymptomatic. Today they are detected by ultrasonography, computerized tomography, or magnetic resonance imaging scan, done for other reasons. Adrenal myelolipomas can be diagnosed because of their characteristic images. Thus they are classified as "incidentalomas." We report the case of a 50-year-old man who had bilateral adrenal myelolipomas and whose right-side tumor was symptomatic. To our knowledge it is the third operated case reported in the literature. A right adrenalectomy was performed, keeping the asymptomatic left adrenal myelolipoma to preserve adrenal function.


A view through a different lens: photovoice as a tool for student advocacy.
To complement National College Health Assessment data and to further assess student lives and health needs, staff at the Rutgers University Health Services' Department of Health Education used a participatory research method called photovoice. Using this methodology, health care professionals provided a discrete and tangible way for students to feel empowered, as the students conducted the project themselves, collecting data using photography, analyzing the results qualitatively, and meeting with policy makers to discuss their photos and offer recommendations for change. Policy recommendations addressed issues of safety, nutrition, sexual health information, alcohol and drugs, and campus parking. In this article, the authors offer a description of this process as another tool for assessment and advocacy.


Uptake and elimination of lindane by Lymnaea palustris (Mollusca: Gastropoda): a pharmacokinetic approach.
The uptake and elimination of lindane by adult Lymnaea palustris (Müller) were studied using a static contamination system. First-order one- and two-compartment models were used to quantitatively describe these phenomena. The accumulation of residues was triphasic and the observed steady-state bioconcentration factor lay between 36.8 and 56.4 but did not significantly depend on the initial lindane concentration (6, 60, and 600 micrograms liter-1). Accumulation was inferior to that observed for other aquatic organisms and this was attributed to the relatively low lipid content of L. palustris tissues (mean of 0.81 +/- 0.17% of fresh weight). The transfer of snails to lindane-free water after 72 hr of exposure was followed by a biphasic elimination of residues with a half-life of 0.7 hr in the central compartment and of 130.2 hr in the peripheral compartment. Additional experiments showed that the residues enter the snails through the foot and are afterward stocked within the visceral mass which contains approximately three times more lipids than the foot (1.03 +/- 0.13% of fresh weight vs 0.37 +/- 0.03%).


Temperature effect of activation energy for GaSb quantum dots using variable temperature photoluminescence.
The excitation power dependence of radiative transitions in the type-II GaSb/GaAs quantum dots structure has been studied by the photoluminescence (PL) at different temperatures. The QDs' photoluminescence exhibits a strong blue-shift with increasing the excitation power and the peak energy (E(PL)) is proportional to the third root of excitation power. With the increase of excitation power, the nonlinear change for both the PL peak and the intensity was observed, which is attributed to the excited state transition. The thermal process and activation energy (E(a)) of electron-hole pairs at different excitation powers has also been studied for GaSb QDs. As the excitation power increases, the activation energy decreases, while E(PL) +E(a) keeps nearly constant, which is smaller than the band gap of GaAs. The decrease of E(a) is probably caused by the band bending effect.


Modulation of CD99/MIC2 expression of human AHTO-7 osteoblasts by carcinoma cell line-conditioned media.
Prostate cancer metastases induce a predominantly osteoblastic response in bone tissue, resulting in new bone formation and associated morbidity; however, the mechanisms of these tumor-host responses are not fully understood. Supernatants of prostate (PC3, DU145, LNCaP), breast (BT20, ZR-75-1), colon (SW620, Colo 320DM), pancreatic (ASPC1, Capan-1), renal cell (ACHN) and hepatoma (HepG2) cell lines were tested for their capacity to modulate proliferation, activity of alkaline phosphatase (ALP) and CD99/MIC2 expression in AHTO-7 (large T antigen transfected human trabecular osteoblasts) cells in vitro. Osteoblastic stimulation is not restricted to prostate cancer derived conditioned media CM and high activity is found in CM from Capan-1, HepG2 and ACHN lines. Furthermore these CM down-regulate the expression of the CD99/MIC2 antigen in comparison to medium by AHTO-7 cells as detected by HBA-71 immunofluorescence, with the exception of prostate cancer-derived CM. Induction of the differentiation marker ALP was detected in response to CM derived from Capan-1, BT-20 and Colo320DM. Stimulation of the proliferation of AHTO-7 cells (105-138% of control), induction of ALP (1.17-5.29-fold) and down-regulation of CD99 (13.6-57.5%) exhibited no correlation. CM derived from PC3 and LNCaP metastatic prostate cancer cell lines specifically resulted in the retention/stimulation of the expression of CD99/MIC2 in AHTO-7 cells in contrast to all other cell lines tested. The CD99/MIC2 antigen, which is expressed on human osteoblasts and osteosarcoma cells, seems to constitute a new and independent response marker of osteoblasts in the triggering of osteoblastic reaction by prostate cancer cells.


A balanced autosomal reciprocal translocation in an azoospermic bull.
This appears to be the first reported case of a bull with a balanced autosomal reciprocal translocation associated with azoospermia. The analysis includes somatic chromosome banding, conventional meiotic analysis, and electron microscopy of synaptonemal complexes (SCs). The karyotype of the bull was found to be 60,XY,rcp(8;13)(q11;q24). Electron microscopy of SCs in microspread pachytene spermatocytes revealed a high incidence of terminal asynapsis of the smallest arm of the quadrivalent. Most quadrivalents with such asynapsis and few with nonhomologous synapsis showed associations with the XY sex bivalent, leading to complete meiotic arrest at late pachynema. Except for one diakinetic cell, no diplotene and subsequent stages were encountered in air-dried meiotic preparations. The presence of degenerating primary spermatocytes in SC preparations, as well as in testicular sections, and the absence of spermatozoa in ejaculates confirm the chromosomally derived male sterility of the bull. X-chromosome reactivation, evidenced by the cytomorphological reversal of associated sex bivalents, appeared to be the initial step in the degeneration of spermatocytes. Consequently, the formation of a separate, fully developed XY body, which was previously demonstrated on the periphery of spermatocyte nuclei in fertile bulls, could not be attained in this case. Extensive end-to-end association of autosomal bivalents in meiotically arrested, as well as degenerating, spermatocytes was a consistent and unique observation of this study. Such associations may lead to enhanced reactivation of the X chromosome.


Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain.
P-glycoprotein (P-gp) is one of the best-known mediators of drug efflux-based multidrug resistance in many cancers. This validated therapeutic target is a prototypic, plasma membrane resident ATP-Binding Cassette transporter that pumps xenobiotic compounds out of cells. The large, polyspecific drug-binding pocket of P-gp recognizes a variety of structurally unrelated compounds. The transport of these drugs across the membrane is coincident with changes in the size and shape of this pocket during the course of the transport cycle. Here, we present the crystal structures of three inward-facing conformations of mouse P-gp derived from two different crystal forms. One structure has a nanobody bound to the C-terminal side of the first nucleotide-binding domain. This nanobody strongly inhibits the ATP hydrolysis activity of mouse P-gp by hindering the formation of a dimeric complex between the ATP-binding domains, which is essential for nucleotide hydrolysis. Together, these inward-facing conformational snapshots of P-gp demonstrate a range of flexibility exhibited by this transporter, which is likely an essential feature for the binding and transport of large, diverse substrates. The nanobody-bound structure also reveals a unique epitope on P-gp.


The effect of maternal canthaxanthin supplementation and hen age on breeder performance, early chick traits, and indices of innate immune function.
Hen age and nutrition influence chick innate immunity. The immunomodulatory antioxidant carotenoid canthaxanthin is transferred from the hen diet to the egg. Antioxidants could protect the chick from bactericidal oxidative species produced by the immune system. Broiler breeder hen diets were supplemented with 0 (Control), 6 (Low), or 12 (High) mg/kg canthaxanthin. Chick early growth and ex vivo innate immunity were measured at 31 to 33 (Early), 45 to 47 (Mid), and 57 to 59 (Late) wk of hen age. Escherichia coli (E. coli) bactericidal capacity, phagocyte activation (number of phagocytes containing at least one E. coli), phagocytic capacity (number of phagocytes containing one or more E. coli), and oxidative burst at 1 and 4 d of age were determined. Egg and chick liver canthaxanthin and chick plasma total antioxidant capacity were measured. Differences were considered significant at P ≤ 0.05. Breeder productivity was greatest for the Low hens; diet did not affect egg yolk, albumen, or shell proportions. Egg canthaxanthin increased with maternal supplementation and plateaued after 28 days, but was not affected by hen age. Chick liver canthaxanthin increased with maternal supplementation, but decreased as hens aged. Hen diet did not affect broiler chick performance to 21 days of age. Maternal canthaxanthin at 6 mg/kg increased chick E. coli bactericidal capacity and d 1 oxidative burst; phagocytosis was unaffected. E. coli bactericidal capacity decreased as hens aged, but increased from 1 to 4 d, indicating maturation of chick innate immunity. Plasma total antioxidant capacity at d 1 increased with maternal canthaxanthin in chicks from Mid and Late hens. Canthaxanthin possesses immuno-modulatory and antioxidant properties, and hen age affected chick innate immune development. Single-comb White Leghorn hens were fed the same levels of canthaxanthin to determine the rate of incorporation into eggs. Egg canthaxanthin reached a plateau after 7 d. Canthaxanthin in the hen diet at 6 mg/kg resulted in the greatest positive effect on hen performance, with little effect on the chick.


Can hypoosmotic shock and calcium influx lead to translocation of aquaporin-1 in shrimp muscle cells?
The physiological variations during the crustacean molting cycle have intrigued researchers for many years. Maintaining osmotic homeostasis in the face of hemolymph dilution and dealing with dynamic intracellular and extracellular calcium fluctuations are challenges these animals continuously confront. It has recently been shown that water channels present in the cell membrane (aquaporins) are essential for water uptake during premolt and postmolt. This study aims to investigate whether hypoosmotic shock and intracellular and extracellular calcium variations can lead to translocation of Aquaporin 1 (AQP-1) from the intracellular region to the plasma membrane during premolt and postmolt, thus allowing increased water flow in these stages. For this, we investigate in vitro the rapid change of AQP-1 positions in the abdominal muscle cells in the freshwater shrimp, Palaemon argentinus. Using cell volume analysis and immunohistochemistry, we show that hypoosmotic conditions and an elevation of the intracellular and extracellular calcium concentrations are concurrent with the translocation of AQP-1 to the plasma membrane. These results indicate that calcium flux and hypoosmotic shock may be regulators of AQP 1 in the translocation process.


Efficient models for enhancing the link adaptation performance of LTE/LTE-A networks.
Link adaptation (LA) is the ability to adapt the modulation scheme (MS) and the coding rate of the error correction in accordance with the quality of the radio link. The MS plays an important role in enhancing the performance of LTE/LTE-A, which is typically dependent on the received signal to noise ratio (SNR). However, using the SNR to select the proper MSs is not enough given that adaptive MSs are sensitive to error. Meanwhile, non-optimal MS selection may seriously impair the system performance and hence degrades LA. In LTE/ LTE-A, the LA system must be designed and optimized in accordance with the characteristics of the physical (e.g., MSs) and MAC layers (e.g., Packet loss) to enhance the channel efficiency and throughput. Accordingly, this study proposes using two LA models to overcome the problem. The first model, named the cross-layer link adaptation (CLLA) model, is based on the downward cross-layer approach. This model is designed to overcome the accuracy issue of adaptive modulation in existing systems and improve the channel efficiency and throughput. The second model, named the Markov decision process over the CLLA (MDP-CLLA) model, is designed to improve on the selection of modulation levels. Besides that, our previous contribution, namely the modified alpha-Shannon capacity formula, is adopted as part of the MDP-CLLA model to enhance the link adaptation of LTE/LTE-A. The effectiveness of the proposed models is evaluated in terms of throughput and packet loss for different packet sizes using the MATLAB and Simulink environments for the single input single output (SISO) mode for transmissions over Rayleigh fading channels. In addition, phase productivity, which is defined as the multiplication of the total throughput for a specific modulation with the difference between adjacent modulation SNR threshold values, is used to determine the best model for specific packet sizes in addition to determine the optimal packet size for specific packet sizes among models. Results generally showed that the throughput improved from 87.5 to 89.6% for (QPSK → 16-QAM) and from 0 to 43.3% for (16-QAM → 64-QAM) modulation transitions, respectively, using the CLLA model when compared with the existing system. Moreover, the throughput using the MDP-CLLA model was improved by 87.5-88.6% and by 0-43.2% for the (QPSK → 16-QAM)and (16-QAM → 64-QAM) modulation transitions, respectively, when compared with the CLLA model and the existing system. Results were also validated for each model via the summation of the phase productivity for every modulation at specific packet sizes, followed by the application one-way analysis of variance (ANOVA) statistical analysis with a post hoc test, to prove that the MDP-CLLA model improves with best high efficiency than the CLLA model and the existing system.


Application of iPS cells derived from congenital myelodysplastic syndrome for research of nomal hematopoesis and hematological malignancies.
Induced pluripotent stem cells (iPSCs) are not only a valuable resource for regenerative medicine, but also a promising tool for disease modeling and drug discovery. Patient-specific iPSCs harboring disease-specific mutations are extremely useful for investigating disease mechanisms and novel treatment approaches. In the field of hematology, attempts to establish iPSCs from tumor cells such as those of leukemia or myelodysplastic syndrome (MDS) were largely unsuccessful because proper reprogramming processes were hampered by their extensive genetic alterations. In contrast, congenital disorders caused by a single genetic mutation are ideal candidates for deriving iPSCs. We have been investigating the molecular mechanisms underlying leukemia and MDS by implementing iPSC technology. Familial platelet disorder (FPD) is a rare autosomal dominant disorder characterized by thrombocytopenia and a high propensity for developing acute leukemia, which is caused by heterozygous mutation of RUNX1. We have successfully established iPSCs from three distinct FPD pedigrees and examined the responsible defect during hematopoietic development. This system will serve as a novel unprecedented platform for prospectively studying hematologic disorders using human cells.


Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.
The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.


Accumulation and inactivation of adenosine by fat cells from hypothyroid rats.
It has been suggested that the deficient lipolytic response to catecholamines in hypothyroidism may be due to an increased sensitivity to adenosine and/or increased adenosine levels in this condition. We confirmed that the addition of adenosine deaminase enhanced the lipolytic response of hypothyroid fat cells, but the stimulation was at least as large in euthyroid cells. Adenosine analogs were more potent as antagonists of NA-induced lipolysis in hypothyroid than in euthyroid fat cells, but the difference could be explained by a decreased response to NA. Suspensions of hypothyroid cells accumulated more purine nucleosides (115 +/- 20) than did euthyroid cells (48 +/- 8 pmol/30 min/10(5) cells; p less than 0.01). This difference could not be explained by a lower rate of adenosine elimination, which occurred by three different pathways: uptake followed by phosphorylation, uptake followed by deamination and deamination by the serum albumin preparation. Under certain circumstances the latter pathway is of overwhelming importance. Fat cells from mature rats (460-480 g) behaved similarly as cells from young control rats. Thus, the changes induced by hypothyroidism was not due to a developmental change. The results are discussed in relation to earlier findings on the alterations in catecholamine responsiveness in hypothyroidism. It is concluded that an increased influence of adenosine could possibly explain some aspects of altered catecholamine responsiveness. If it does the mechanism is likely to involve an enhanced amount of adenosine rather than an increased sensitivity to adenosine.


Targeting Ribosome Biogenesis to Combat Tamoxifen Resistance in ER+ve Breast Cancer.
Breast cancer is a heterogeneous disease. Around 70% of breast cancers are estrogen receptor-positive (ER+ve), with tamoxifen being most commonly used as an adjuvant treatment to prevent recurrence and metastasis. However, half of the patients will eventually develop tamoxifen resistance. The overexpression of c-MYC can drive the development of ER+ve breast cancer and confer tamoxifen resistance through multiple pathways. One key mechanism is to enhance ribosome biogenesis, synthesising mature ribosomes. The over-production of ribosomes sustains the demand for proteins necessary to maintain a high cell proliferation rate and combat apoptosis induced by therapeutic agents. c-MYC overexpression can induce the expression of eIF4E that favours the translation of structured mRNA to produce oncogenic factors that promote cell proliferation and confer tamoxifen resistance. Either non-phosphorylated or phosphorylated eIF4E can mediate such an effect. Since ribosomes play an essential role in c-MYC-mediated cancer development, suppressing ribosome biogenesis may help reduce aggressiveness and reverse tamoxifen resistance in breast cancer. CX-5461, CX-3543 and haemanthamine have been shown to repress ribosome biogenesis. Using these chemicals might help reverse tamoxifen resistance in ER+ve breast cancer, provided that c-MYC-mediated ribosome biogenesis is the crucial factor for tamoxifen resistance. To employ these ribosome biogenesis inhibitors to combat tamoxifen resistance in the future, identification of predictive markers will be necessary.


Cystometric, physiological and morphological studies after relief of bladder outflow obstruction in the pig.
Experimental bladder outflow obstruction was relieved in 18 pigs between 2 and 15 months after the creation of partial urethral obstruction. Cystometric, physiological and morphological studies were performed 2 to 6 months after relief of the obstruction. An increase in average voiding flow rates from 2.8 +/- 1.0 ml/s to 6.8 +/- 1.2 ml/s was recorded in the Landrace pigs and from 2.2 +/- 0.9 ml/s to 7.4 +/- 1.4 ml/s in the Göttingen mini-pigs. There was a concomitant decrease in the voiding detrusor pressures from 52 +/- 11 cm H2O to 32 +/- 8 cm H2O and from 78 +/- 12 cm H2O to 33 +/- 6 cm H2O respectively. A return towards control values of the physiological responses to exogenously applied agonists (acetylcholine and potassium) and to electrical field stimulation was observed. There was an increase in neuronal innervation in the morphological studies which was more marked in the animals with a shorter period of obstruction. The implications for patient care are discussed.


Spatial and seasonal patterns in climate change, temperatures, and precipitation across the United States.
Changes in climate during the 20th century differ from region to region across the United States. We provide strong evidence that spatial variations in US temperature trends are linked to the hydrologic cycle, and we also present unique information on the seasonal and latitudinal structure of the linkage. We show that there is a statistically significant inverse relationship between trends in daily temperature and average daily precipitation across regions. This linkage is most pronounced in the southern United States (30-40 degrees N) during the May-June time period and, to a lesser extent, in the northern United States (40-50 degrees N) during the July-August time period. It is strongest in trends in maximum temperatures (T(max)) and 90th percentile exceedance trends (90PET), and less pronounced in the T(max) 10PET and the corresponding T(min) statistics, and it is robust to changes in analysis period. Although previous studies suggest that areas of increased precipitation may have reduced trends in temperature compared with drier regions, a change in sign from positive to negative trends suggests some additional cause. We show that trends in precipitation may account for some, but not likely all, of the cause point to evidence that shows that dynamical patterns (El Niño/Southern Oscillation, North Atlantic Oscillation, etc.) cannot account for the observed effects during May-June. We speculate that changing aerosols, perhaps related to vegetation changes, and increased strength of the aerosol direct and indirect effect may play a role in the observed linkages between these indices of temperature change and the hydrologic cycle.


Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial.
To evaluate the influence of the methylxanthine derivative, pentoxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in prematurely delivered infants with generalized bacterial infections and to assess the effect of this immunomodulating drug on the clinical outcome in newborns with sepsis. A prospective, randomized, double-blind trial. The neonatal intensive therapy units in university teaching hospitals. One hundred patients with sepsis admitted during a 1.5-yr period. Patients were randomly assigned to receive pentoxifylline (pentoxifylline group) in a dose of 5 mg/kg/hr for 6 hrs on 6 successive days or an identically presented placebo (placebo group). Only infants with sepsis confirmed by positive blood culture were recruited into the study. There were no significant differences at randomization between the pentoxifylline and placebo groups with regard to the birth weight, gestational age, gender, Apgar score, hypotension, neutropenia, thrombocytopenia, metabolic acidosis, plasma levels of cytokines, and occurrence of shock. Plasma levels of TNF, IL-1, and IL-6 were evaluated before and after the drug or placebo administration on the first, third, and sixth days of therapy. Cytokines were determined by immunoenzymetric test EASIA (TNF) and Endogen Interleukin-Elisa (IL-1, IL-6). The frequency of gram-negative sepsis was similar in both groups (37.5% and 36.8%). Pentoxifylline significantly diminished plasma TNF levels (p = .009) but had no effect on plasma IL-1 levels. Mean plasma IL-6 levels, which were measured in the pentoxifylline group on the 6th day of the study, were significantly lower compared with respective data obtained in the placebo group. Only 1 of 40 infants with sepsis in the pentoxifylline group died, whereas 6 of 38 infants in the placebo group did not survive (p = .046). An increased incidence of disordered peripheral circulation and metabolic acidosis (p = .048), anuria or oliguria (p = .03), disseminated intravascular coagulation (p = .043), and the occurrence of clinical symptoms of necrotizing enterocolitis (p = .025) was observed in the course of sepsis in infants in the placebo group. Pentoxifylline significantly affects the synthesis of TNF and IL-6 as well as reduces the mortality rate in premature infants with sepsis. The dosage and schedule of drug administration in this study attenuated the severity of the clinical course of sepsis in this group of patients.


In loving memory of 'us': facing grief during the time of COVID-19 through redirecting perception of life's realities.
Recent correspondence highlighted the complicated process of grief in the time of COVID-19 where some family members and the dying person too are undergoing distress. New rituals can lighten the process of coping with grief or death, one may find it difficult to hurdle such situation and move on without first redirecting one's perception on the different realities of life. There are things that we can control but at the same time, things that are beyond our reach. With these realities, acceptance plays a key role to handle the situation. Acceptance is a person's assent to life's realities. Creativity in accepting grief or death is finding ways to lighten the heavy emotion of the 'ones left and the one leaving' through a preservation of memory. This is done through safeguarding and reliving the memories of the dead with various programs and advocacies.


Speciation of ferric phenoxide intermediates during the reduction of iron(III)-μ-oxo dimers by hydroquinone.
The aqueous speciation of iron(III)-tris(pyridylmethyl)amine (TPA) complexes was determined from potentiometric titration data, and the overall formation constants (β) for relevant species were calculated. At pH < 3 the mononuclear complex [Fe(TPA)](+3)(aq) predominates (log β = 10.75(15). Above pH 3 Fe(3+)-OH2 hydrolysis produces the μ-oxo dimer [Fe2(μ-O)(TPA)2(H2O)2](+4) (1a; log β = 19.91(12)). This species is a diprotic acid with the conjugate bases [Fe2(μ-O)(TPA)2(H2O)(OH)](+3) (1b; log β = 15.53(6)) and [Fe2(μ-O)(TPA)2(OH)2](+2) (1c; log β = 10.27(7)). The pKas of 1a are 4.38(14) and 5.26(9). Compounds 1a-c quantitatively oxidize hydroquinone to benzoquinone with concomitant formation of 2 equiv of Fe(II). Kinetic and spectroscopic data at pH 5.6 are consistent with rapid equilibrium formation of a diiron(III)-phenoxide intermediate followed by rate-controlling electron transfer. The equilibrium constant for the formation of the intermediate complex is 25(3) M(-1), and the rate constant for its decomposition is 0.56(9) s(-1). A kinetic isotope effect of kH/kD = 1.5 was determined from proton inventory experiments in mixed H/D media. The μ-oxo-diiron(III) phenoxide intermediate is hydrolyzed in a pH dependent process to form a mononuclear iron(III)-phenoxide, which complicates the kinetics by introducing a fractional dependence on total iron(III) concentration in the pH range 4.1-5.2. The pH-dependent cleavage of μ-oxo-diiron(III)-phenoxides was investigated with phenol, a redox-inert proxy for hydroquinone. The addition of phenol to 1 facilitates acidic cleavage of the μ-oxo dimer to form [Fe(TPA)(OPh)(H2O)](+2), which becomes the dominant iron(III)-phenoxide as the pH decreases to 4. The 2-naphtholate analogue of this intermediate, [Fe(TPA)(2-naphtholate)(OCH3)]ClO4 (6), was characterized by single-crystal X-ray diffraction (C29H28FeN4O2,ClO4; P21; a = 13.2646(2) Å, b = 15.2234(3) Å, c = 13.7942(3) Å; Z = 4).


Obesity and metabolic syndrome during the menopause transition in Serbian women.
Abdominal obesity and metabolic syndrome are known to increase in prevalence from premenopause to postmenopause. Both are well recognized predictors of cardiovascular disease and diabetes in women. Aims The primary objective of this study was to assess the presence of obesity and metabolic syndrome during the menopause transition in Serbian women who attended health-care centers. The secondary objective was to evaluate the prevalence of ischemic heart disease, stroke and diabetes in this group. Our results present a part of the national epidemiological cross-sectional study assessing prevalence of metabolic syndrome and obesity in Serbia. In all, 1076 women attending 20 health-care centers were assessed. Women were divided into five groups: premenopausal, perimenopausal, early and late postmenopausal and geripausal. Medical history, waist circumference, blood glucose, lipids, and blood pressure were recorded. The mean body mass index of all women was 28.5 ± 4.9 kg/m(2). The mean waist circumference of all women was 92 ± 12.5 cm. Both were significantly lower in premenopausal women than in other women. Metabolic syndrome was present in 72% of women, with a significant difference in prevalence between premenopausal women and other groups. High triglyceride levels and hypertension were the most commonly present components of metabolic syndrome. Ischemic heart disease, stroke and diabetes occurred significantly more often in postmenopausal and geripausal women. The majority of Serbian women attending health-care centers have abdominal obesity and metabolic syndrome which significantly increase in prevalence in the perimenopausal years. This indicates that preventive measures should be focused on diabetes and cardiovascular disease in the perimenopause.


Evaluation of health in pregnancy grants in Scotland: a protocol for a natural experiment.
A substantial proportion of low birth weight is attributable to the mother's cultural and socioeconomic circumstances. Early childhood programmes have been widely developed to improve child outcomes. In the UK, the Health in Pregnancy (HiP) grant, a universal conditional cash transfer of £190, was introduced for women reaching the 25th week of pregnancy with a due date on/or after 6 April 2009 and subsequently withdrawn for women reaching the 25th week of pregnancy on/or after 1 January 2011. The current study focuses on the evaluation of the effectiveness and cost-effectiveness of the HiP grant. The population under study will be all singleton births in Scotland over the periods of January 2004 to March 2009 (preintervention), April 2009 to April 2011 (intervention) and May 2011 to December 2013 (postintervention). Data will be extracted from the Scottish maternity and neonatal database. The analysis period 2004-2013 should yield over 585,000 births. The primary outcome will be birth weight among singleton births. Other secondary outcomes will include gestation at booking, booking before 25 weeks; measures of size and stage; gestational age at delivery; weight-for-dates, term at birth; birth outcomes and maternal smoking. The main statistical method we will use is interrupted time series. Outcomes will be measured on individual births nested within mothers, with mothers themselves clustered within data zones. Multilevel regression models will be used to determine whether the outcomes changed during the period in which the HiP grants was in effect. Subgroup analyses will be conducted for those groups most likely to benefit from the payments. Approval for data collection, storage and release for research purpose has been given (6 May 2014, PAC38A/13) by the Privacy Advisory Committee. The results of this study will be disseminated through peer-reviewed publications in journals, national and international conferences.


[Complete resolution of inflammatory myofibroblastic tumor of the bladder after antibiotic therapy].
Inflammatory myofibroblastic tumors (IMT) are rare benign tumors, most commonly arising in the lungs and urinary bladder. Many etiologic factors are suspected in their development, but none have been formally demonstrated. Conventional treatment for bladder IMT is complete surgical resection by partial cystectomy or transurethral resection. We report the case of an 8-year-old girl with documented bladder IMT that resolved completely after antibiotic therapy.


Spinal cord compression in metastatic cervical cancer.
Spinal cord compression secondary to metastatic cervical cancer may not be considered as a possible cause of neurologic symptoms by primary care physicians who do not often treat these patients. Delays in diagnosis and treatment may result in irreversible but potentially preventable neurologic changes. This report describes 5 cases of spinal cord compression in patients with metastatic cervical carcinoma, 2 of whom were previously undiagnosed with cervical cancer. These 2 patients represent 1.6% (2 of 121) of all new cervical cancer cases diagnosed during this time period. Two of 5 patients (40%) with spinal cord compression showed improvement following therapy by regaining the ability to walk, while none of the remaining patients had further acute deterioration of neurologic function. The mean survival of patients presenting with spinal cord compression from cervical cancer in this series was 4 months (maximum 6 months). This series illustrates the relative frequency with which spinal cord compression is seen in patients with a new diagnosis of invasive cancer. This diagnosis should be considered when evaluating neurologic complaints in known cervical cancer patients or any woman with apparent pelvic pathology. Rapid diagnosis and treatment of these lesions, while not likely to improve overall survival significantly, can improve function and alleviate symptoms.


Improving the extensor lag and range of motion following free vascularized joint transfer to the proximal interphalangeal joint: Part 1. An observational and cadaveric study.
Extension lag is a common occurrence following free vascularized joint transfer reconstruction of the proximal interphalangeal joint, thus limiting the range of motion that is achievable. In this Part 1 study, the anatomical and biomechanical arrangements of the toe proximal interphalangeal joint extensor mechanism were investigated. Twelve second toes from 12 fresh cadavers were dissected for examination of the extensor mechanism. Similar observations were performed in nine clinical cases. A total of 21 toes were therefore examined with dynamic and static testing. In 17 toes, the central tendon attenuated before inserting onto the middle phalangeal base (type I). In four toes, a thicker tendinous insertion analogous to a central slip was identified (type II). In type I toes, traction of the extensor digitorum brevis and digitorum longus did not correct the extensor lag. The extension lag decreased when the metatarsophalangeal joint was flexed passively or when both extrinsic and intrinsic tendons were pulled simultaneously. In type II toes, a full extension of the proximal interphalangeal joint was achieved when the extensor tendons were pulled with or without pulling the intrinsic tendons. In both types of toes, there was an increase in the extension lag caused by dorsal bowstringing when separated from the extensor sling. The lesser toe proximal interphalangeal joint adopts a naturally flexed posture for evolutionary reasons, with corresponding adaptations in extensor mechanism arrangements. The most significant limiting factor to full extension could be the presence of an attenuated central slip in the majority of toes.


Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.
Small molecule drugs known as modulators can treat ~90% of people with cystic fibrosis (CF), but do not work for premature termination codon variants such as W1282X (c.3846G>A). Here we evaluated two gene editing strategies, Adenine Base Editing (ABE) to correct W1282X, and Homology-Independent Targeted Integration (HITI) of a CFTR superexon comprising exons 23-27 (SE23-27) to enable expression of a CFTR mRNA without W1282X. In Flp-In-293 cells stably expressing a CFTR expression minigene bearing W1282X, ABE corrected 24% of W1282X alleles, rescued CFTR mRNA from nonsense mediated decay and restored protein expression. However, bystander editing at the adjacent adenine (c.3847A>G), caused an amino acid change (R1283G) that affects CFTR maturation and ablates ion channel activity. In primary human nasal epithelial cells homozygous for W1282X, ABE corrected 27% of alleles, but with a notably lower level of bystander editing, and CFTR channel function was restored to 16% of wild-type levels. Using the HITI approach, correct integration of a SE23-27 in intron 22 of the CFTR locus in 16HBEge W1282X cells was detected in 5.8% of alleles, resulting in 7.8% of CFTR transcripts containing the SE23-27 sequence. Analysis of a clonal line homozygous for the HITI-SE23-27 produced full-length mature protein and restored CFTR anion channel activity to 10% of wild-type levels, which could be increased three-fold upon treatment with the triple combination of CF modulators. Overall, these data demonstrate two different editing strategies can successfully correct W1282X, the second most common class I variant, with a concomitant restoration of CFTR function.


Is There a Need for a Pulmonary Artery Catheter in Cardiac Surgery Today?
Pulmonary artery catheters are a useful tool for hemodynamic monitoring in high-risk patients during surgery and while in intensive care. However, there are major risks inherent to the device, and with modern day technology, their routine use has decreased. We discuss the need for routine insertion of pulmonary artery catheters in cardiac surgery. We also present a case of a left ventricular assist device implantation complicated by serious pulmonary hemorrhage due to pulmonary artery catheter insertion, highlighting the potentially life-threatening risks involved.


Comparison of CEA, MCA, CA 15-3 and CA 27-29 in follow-up and monitoring therapeutic response in breast cancer patients.
In order to define the most useful tumor marker panel in breast cancer patients' follow-up and in monitoring treatment response, serological levels of CEA, MCA, Ca 15-3 and Ca 27-29 were evaluated in 220 patients. 180 patients had no evidence of disease (NED) after primary treatment, and 40 had metastases at first diagnosis time; in a 4 years follow-up, 30 of the NED patients relapsed, and were then included in the group of metastatic patients subjected to anticancer treatment. Overall sensitivity in metastatic patients was: CEA 40%, MCA 35%, Ca 15-3 79%, Ca 27-29 70%, with the highest percentages and mean values in liver and bone localizations. Combination of Ca 15-3 and Ca 27-29 improved sensitivity in bone lesion (85% vs 80%), in locoregional relapses only association with CEA increased sensitivity (60% vs 40%). Ca 15-3 and Ca 27-29 values increased on average 3 months before clinical diagnosis. In treated patients there was a better correlation with a clinical course of disease for Ca 15-3 and Ca 27-29 (both 81%) as compared to the other determined markers.


Children's Perception of Research Participation: Examining Trauma Exposure and Distress.
USING THE REACTIONS TO RESEARCH Participation Questionnaire for Children (RRPQ-C), this study examined perceptions of research participation among 181 school-aged children with and without trauma histories. As part of two larger studies, children completed non-trauma related tasks to assess emotion understanding and cognitive ability. Parents (and not children) reported on children's interpersonal (e.g., sexual abuse, physical abuse, witnessing domestic violence, witnessing community violence) and non-interpersonal (e.g., motor vehicle accidents, medical traumas, natural disasters) trauma exposure. Children's perceptions of costs and benefits of research participation and understanding of informed consent did not vary as a function of trauma exposure. The number of traumatic events experienced was unrelated to children's perceptions. Furthermore, children across trauma-exposure groups generally reported a positive cost-benefit ratio, and understanding of the consent information. Implications of these data are discussed.


Social resources and longevity: findings from the Georgia centenarian study.
As the proportion of adults aged 85 and older increases, investigations of resources essential for adapting to the challenges of aging are required. To comprehensively investigate the social resources of cognitively intact centenarians participating in the Georgia Centenarian Study and the association between these resources and residence status. Two widely used measures of social resources were investigated among participants living in private homes, personal care facilities, and nursing homes. Logistic regression was used to determine significant predictors of nursing home residence. Differences in levels of social resources were found between centenarians and octogenarians, and among centenarians in different living situations. Analyses revealed differential findings between self- and proxy reports. Controlling for education, activities of daily living, and financial ability to meet needs, only one of the two social resources measures significantly reduced the odds of nursing home residence. The findings of this study add to the existing literature on one of the basic adaptive resources (social resources) for centenarians. Whether a more specific assessment of network contact is employed, or a more global assessment is used, differences in these constructs exist between centenarians and octogenarians, among centenarians in differing living conditions, and across types of informants. Researchers examining the different resources that may contribute to extraordinary longevity and positive adaptation may find it essential to differentiate between the oldest old and centenarians, and to account for differences based upon measure, reporter type, and centenarian residence status.


Freeze-thaw approach: A practical sample preparation strategy for residue analysis of multi-class veterinary drugs in chicken muscle.
Seven drugs from different classes, namely, fluoroquinolones (enrofloxacin, ciprofloxacin, sarafloxacin), sulfonamides (sulfadimidine, sulfamonomethoxine), and macrolides (tilmicosin, tylosin), were used as test compounds in chickens by oral administration, a simple extraction step after cryogenic freezing might allow the effective extraction of multi-class veterinary drug residues from minced chicken muscles by mix vortexing. On basis of the optimized freeze-thaw approach, a convenient, selective, and reproducible liquid chromatography with tandem mass spectrometry method was developed. At three spiking levels in blank chicken and medicated chicken muscles, average recoveries of the analytes were in the range of 71-106 and 63-119%, respectively. All the relative standard deviations were <20%. The limits of quantification of analytes were 0.2-5.0 ng/g. Regardless of the chicken levels, there were no significant differences (P > 0.05) in the average contents of almost any of the analytes in medicated chickens between this method and specific methods in the literature for the determination of specific analytes. Finally, the developed method was successfully extended to the monitoring of residues of 55 common veterinary drugs in food animal muscles.


A New Bearing Fault Diagnosis Method Based on Capsule Network and Markov Transition Field/Gramian Angular Field.
Compared to time-consuming and unreliable manual analysis, intelligent fault diagnosis techniques using deep learning models can improve the accuracy of intelligent fault diagnosis with their multi-layer nonlinear mapping capabilities. This paper proposes a model to perform fault diagnosis and classification by using a time series of vibration sensor data as the input. The model encodes the raw vibration signal into a two-dimensional image and performs feature extraction and classification by a deep convolutional neural network or improved capsule network. A fault diagnosis technique based on the Gramian Angular Field (GAF), the Markov Transition Field (MTF), and the Capsule Network is proposed. Experiments conducted on a bearing failure dataset from Case Western Reserve University investigated the impact of two coding methods and different network structures on the diagnosis accuracy. The results show that the GAF technique retains more complete fault characteristics, while the MTF technique contains a small number of fault characteristics but more dynamic characteristics. Therefore, the proposed method incorporates GAF images and MTF images as a dual-channel image input to the capsule network, enabling the network to obtain a more complete fault signature. Multiple sets of experiments were conducted on the bearing fault dataset at Case Western Reserve University, and the Capsule Network in the proposed model has an advantage over other convolutional neural networks and performs well in the comparison of fault diagnosis methods proposed by other researchers.


[Scleritis - Progress in Diagnosis and Therapy].
Inflammation of the sclera includes a wide range of morphological changes, which often occur in association with systemic diseases. While episcleritis is mainly harmless, scleritis often proceeds and is characterised by a destructive course. This may lead to important complications, that present as ulcerative keratitis, uveitis or secondary increases in intraocular pressure. As this form of inflammation is severe and there are often underlying diseases, this contribution focusses on differential diagnosis and current therapeutic approaches.


Relationships between calcium and pH in the regulation of the slow afterhyperpolarization in cultured rat hippocampal neurons.
The Ca(2+)-dependent slow afterhyperpolarization (AHP) is an important determinant of neuronal excitability. Although it is established that modest changes in extracellular pH (pH(o)) modulate the slow AHP, the relative contributions of changes in the priming Ca(2+) signal and intracellular pH (pH(i)) to this effect remain poorly defined. To gain a better understanding of the modulation of the slow AHP by changes in pH(o), we performed simultaneous recordings of intracellular free calcium concentration ([Ca(2+)](i)), pH(i), and the slow AHP in cultured rat hippocampal neurons coloaded with the Ca(2+)- and pH-sensitive fluorophores fura-2 and SNARF-5F, respectively, and whole cell patch-clamped using the perforated patch technique. Decreasing pH(o) from 7.2 to 6.5 lowered pH(i), reduced the magnitude of depolarization-evoked [Ca(2+)](i) transients, and inhibited the subsequent slow AHP; opposite effects were observed when pH(o) was increased from 7.2 to 7.5. Although decreases and increases in pH(i) (at a constant pH(o)) reduced and augmented, respectively, the slow AHP in the absence of marked changes in preceding [Ca(2+)](i) transients, the inhibition of the slow AHP by decreases in pH(o) was correlated with low pH(o)-dependent reductions in [Ca(2+)](i) transients rather than the decreases in pH(i) that accompanied the decreases in pH(o). In contrast, high pH(o)-induced increases in the slow AHP were correlated with the accompanying increases in pH(i) rather than high pH(o)-dependent increases in [Ca(2+)](i) transients. The results indicate that changes in pH(o) modulate the slow AHP in a manner that depends on the direction of the pH(o) change and substantiate a role for changes in pH(i) in modulating the slow AHP during changes in pH(o).


A molecular genetic dissection of the evolutionarily conserved N terminus of yeast Rad52.
Rad52 is a DNA-binding protein that stimulates the annealing of complementary single-stranded DNA. Only the N terminus of Rad52 is evolutionarily conserved; it contains the core activity of the protein, including its DNA-binding activity. To identify amino acid residues that are important for Rad52 function(s), we systematically replaced 76 of 165 amino acid residues in the N terminus with alanine. These substitutions were examined for their effects on the repair of gamma-ray-induced DNA damage and on both interchromosomal and direct repeat heteroallelic recombination. This analysis identified five regions that are required for efficient gamma-ray damage repair or mitotic recombination. Two regions, I and II, also contain the classic mutations, rad52-2 and rad52-1, respectively. Interestingly, four of the five regions contain mutations that impair the ability to repair gamma-ray-induced DNA damage yet still allow mitotic recombinants to be produced at rates that are similar to or higher than those obtained with wild-type strains. In addition, a new class of separation-of-function mutation that is only partially deficient in the repair of gamma-ray damage, but exhibits decreased mitotic recombination similar to rad52 null strains, was identified. These results suggest that Rad52 protein acts differently on lesions that occur spontaneously during the cell cycle than on those induced by gamma-irradiation.


[Magnesium content of serum in pregnancy-induced hypertension].
Magnesium concentrations were measured in the serum of 159 pregnant women, 19 patients with severe, 64 with mild gestational hypertension and 76 with a normal pregnancy. Our data do not support the conclusion that magnesium deficiency is the primary cause of gestational hypertension.


Clinical comparison of sevoflurane and isoflurane in healthy patients.
We compared blood pressure and heart rate changes in healthy patients during anesthesia with sevoflurane (n = 50) versus isoflurane (n = 25) and the rate of recovery after such anesthesia. After premedication with intravenous administration of midazolam, induction of anesthesia with thiopental, and intubation of the trachea facilitated with succinylcholine or vecuronium, anesthesia was maintained with approximately 1 MAC (sevoflurane, 2.05%; isoflurane, 1.15%) of the volatile anesthetic in oxygen for the duration of the operation. Anesthetic concentration was varied as indicated to maintain arterial blood pressure at +/- 20% of baseline values. Sevoflurane and isoflurane produced similar systolic and diastolic arterial blood pressures, but heart rate after incision was faster in patients given isoflurane. Recovery of response to command was shorter in patients given sevoflurane than that in patients given isoflurane (7.5 +/- 0.5 min versus 18.6 +/- 2.0 min). Consistent with this finding, venous blood drawn after anesthesia showed a more rapid initial decay with sevoflurane. Nausea and vomiting were comparable in both groups. We conclude that sevoflurane anesthesia, as compared with isoflurane, is associated with possible advantageous effects on heart rate and recovery.


Expression and significance of Musashi-1 in gastric cancer and precancerous lesions.
To investigate expression of stem cell marker Musashi-1 (Msi-1) in relationship to tumorigenesis and progression of intestinal-type gastric cancer (GC). Endoscopic biopsy specimens and surgical specimens were obtained, including 54 cases of intestinal-type GC, 41 high-grade intraepithelial neoplasia, 57 low-grade intraepithelial neoplasia, 31 intestinal metaplasia, and 36 normal gastric mucosa. Specimens were fixed in 10% paraformaldehyde, conventionally dehydrated, embedded in paraffin, and sliced in 4-μm-thick serial sections. Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen (PCNA) expression. Correlation analysis was conducted between Msi-1 and PCNA expression. The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically. There were significant differences in Msi-1 and PCNA expression in different pathological tissues (χ² = 15.37, P < 0.01; χ² = 115.36, P < 0.01). Msi-1 and PCNA-positive cells were restricted to the isthmus of normal gastric glands. Expression levels of Msi-1 and PCNA in intestinal metaplasia were significantly higher than in normal mucosa (U = 392.0, P < 0.05; U = 40.50, P < 0.01), whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia. Msi-1 and PCNA expression in intestinal-type GC was higher than in high-grade intraepithelial neoplasia (U = 798.0, P < 0.05; U = 688.0, P < 0.01). There was a significantly positive correlation between Msi-1 and PCNA expression (r(s) = 0.20, P < 0.01). Msi-1 expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage (χ² = 12.62, P < 0.01; χ² = 11.24, P < 0.05), but not with depth of invasion and the presence of distant metastasis. Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.


Hemophilia: A Review of Perioperative Management for Cardiac Surgery.
Hemophilia is an X-linked, recessive bleeding disorder. Improvements in factor replacement therapy and overall approach to hemophilia management have increased the lifespan and quality of life for patients with hemophilia. Thus, they are presenting for cardiac surgery related to age-related atherosclerosis, vascular disorders, and degenerative valvular disease. Although challenging, cardiac surgery can be performed safely with appropriate planning, using a multidisciplinary approach. This article provides a narrative review and framework for the perioperative management of patients with hemophilia A and B undergoing cardiac surgery.


[Pure red cell aplasia complicated with polyarthritis, angitis, and acute renal failure].
A case of pure red cell aplasia (PRCA) with various complications polyarthritis, angitis, acute renal failure and DIC was successfully treated with steroid pulse therapy was described. A 55-year-old woman was hospitalized with a 9-month of intermittent but progressive joint pain, morning stiffness, general fatigue, and fever. Her initial laboratory evaluation revealed a hemoglobin of 4.4 g/dl and absence of reticulocyte. Her bone marrow aspirate showed no erythroblast which was compatible with a diagnosis of PRCA. Marked leukocytosis and thrombocytosis, positive antinuclear antigen, elevation of gammaglobulin and C-reactive protein and the presence of polyarthritis and angitis which was confirmed by renal angiography, indicated an underlying autoimmune disorders. Steroid pulse therapy was administered at 500 mg/day for 3 days, resulting in the complete response in both red cell aplasia and above findings. PRCA is known to be associated with systemic lupus erythematosus and rheumatoid arthritis very rarely, but this case did not fulfill the criteria of known collagen diseases, and there is no previous report representing PRCA with various complications such as polyarthritis, angitis and acute renal failure. This case may help us to understand more about the relationship between PRCA and autoimmune disorders.


Evidence for simultaneous sound production in the bowhead whale (Balaena mysticetus).
Simultaneous production of two harmonically independent sounds, the two-voice phenomenon, is a well-known feature in bird song. Some toothed whales can click and whistle simultaneously, and a few studies have also reported simultaneous sound production by baleen whales. The mechanism for sound production in toothed whales has been largely uncovered within the last three decades, whereas mechanism for sound production in baleen whales remains poorly understood. This study provides three lines of evidence from recordings made in 2008 and 2009 in Disko Bay, Western Greenland, strongly indicating that bowhead whales are capable of simultaneous dual frequency sound production. This capability may function to enable more complex singing in an acoustically mediated reproductive advertisement display, as has been suggested for songbirds, and/or have significance in individual recognition.


Post-transcriptional regulation of cystic fibrosis transmembrane conductance regulator expression and function by microRNAs.
MicroRNAs (miRNAs) are increasingly recognized as important posttranscriptional regulators of gene expression, and changes in their actions can contribute to disease states. Little is understood regarding miRNA functions in the airway epithelium under normal or diseased conditions. We profiled miRNA expression in well-differentiated primary cultures of human cystic fibrosis (CF) and non-CF airway epithelia, and discovered that miR-509-3p and miR-494 concentrations were increased in CF epithelia. Human non-CF airway epithelia, transfected with the mimics of miR-509-3p or miR-494, showed decreased cystic fibrosis transmembrane conductance regulator (CFTR) expression, whereas their respective anti-miRs exerted the opposite effect. Interestingly, the two miRNAs acted cooperatively in regulating CFTR expression. Upon infecting non-CF airway epithelial cells with Staphylococcus aureus, or upon stimulating them with the proinflammatory cytokines TNF-α or IL-1β, we observed an increased expression of both miRNAs and a concurrent decrease in CFTR expression and function, suggesting that inflammatory mediators may regulate these miRNAs. Transfecting epithelia with anti-miRs for miR-509-3p and miR-494, or inhibiting NF-κB signaling before stimulating cells with TNFα or IL-1β, suppressed these responses, suggesting that the expression of both miRNAs was responsive to NF-κB signaling. Thus, miR-509-3p and miR-494 are dynamic regulators of CFTR abundance and function in normal, non-CF airway epithelia.


The effect of health education interventions on child malaria treatment-seeking practices among mothers in rural refugee villages in Belize, Central America.
This paper reports on a study conducted to examine the effect of health education interventions on mothers' treatment-seeking behaviors for their children's malaria fevers. The study used a quasi-experimental post-test community-based design with an intervention and control group. A post-intervention survey was conducted to assess knowledge, attitudes and child fever and malaria treatment-seeking behaviors and access and exposure to health messages. Survey results indicated that some health education interventions, especially interpersonal communication, appeared to have a positive impact on fever and malaria beliefs and attitudes and on positive treatment-seeking behaviors. While some interventions appeared to have a positive impact on fever and malaria beliefs and attitudes and on positive treatment-seeking behaviors, limitations in the study design made assigning specific effects to the interventions difficult. However, health education interventions remain a valuable tool in addressing malaria in children.


Outcomes of salvage procedures for occluded autogenous radiocephalic arteriovenous fistula.
The outcomes of surgical and endovascular treatments for thrombosed access fistulas are variable and provide no definitive indications for treatment choice. We purposed to review our experience in treating thrombosed radiocephalic arteriovenous fistulas (AVFs) and to evaluate the outcome of procedures, including proximal neo-anastomosis (NEO), replacement of the stenosed segment with a polytetrafluoroethylene graft (GI), patch angioplasty (PA), and endovascular procedures (such as percutaneous transluminal angioplasty [PTA]). A total of 117 occluded radiocephalic AVFs were treated by surgery or an endovascular procedure from January 2002 to December 2007. We evaluated the rates of initial success, re-thrombosis, the post-interventional five-year patency rate, and temporary catheter requirement. Forty-five patients (38.5%) underwent NEO, 32 patients (27.4%) GI, 10 patients (8.5%) PA, and 30 patients (25.6%) PTA. The overall initial procedural success rate was 98.3% (surgery 98.9% and PTA 96.7%), and the post-interventional patency rates at five years were 92.2% (97.1% for NEO, 82.7% for GI, 90.0% for PA, and 96.7% for PTA). Twenty-four patients (20.5%) required a temporary catheter during healing of the functioning segment after treatment: four patients for NEO, 18 patients for GI, two patients for PA, and no patients for PTA (P < 0.001). Both surgery and endovascular treatment gave high rates of initial success and low re-thrombosis rates as salvage treatments for occlusion of radiocephalic AVFs, if treatments were selected according to the length, and location of the stenosis to be corrected. When stenosis of a long segment is suspected, endovascular treatment should be attempted first in order to maintain the functional segment and thereby avoid use of a temporary catheter.


Detection and characterization of tick-borne encephalitis virus in Baltic countries and eastern Poland.
Ticks were collected from the vegetation in the Baltic countries Estonia, Latvia, Lithuania and eastern Poland and analyzed for the presence of tick-borne encephalitis virus (TBEV) by amplification of the partial E and NS3 genes. In Estonia we found statistically significant differences in the TBEV prevalence between I. persulcatus and I. ricinus ticks (4.23% and 0.42%, respectively). In Latvia, the difference in TBEV prevalence between the two species was not statistically significant (1.02% for I. persulcatus and 1.51% for I. ricinus, respectively). In Lithuania and Poland TBEV was detected in 0.24% and 0.11% of I. ricinus ticks, respectively. Genetic characterization of the partial E and NS3 sequences demonstrated that the TBEV strains belonged to the European subtype in all countries, as well as to the Siberian subtype in Estonia. We also found that in areas where ranges of two tick species overlap, the TBEV subtypes may be detected not only in their natural vector, but also in sympatric tick species.


The response of the anterior pituitary and testes to synthetic luteinizing hormone-releasing hormone (LHRH) and the effect of castration on pituitary responsiveness in the maturing chicken fed aflatoxin.
The responsiveness of the anterior pituitary to exogenous luteinizing hormone-releasing hormone (LHRH; 20 micrograms/kg body weight) and the subsequent stimulation of testosterone secretion by the testes was studied after administration of dietary aflatoxin (10 ppm) to 9-wk-old male chickens. In both control and aflatoxin-treated males, there were significant (p less than 0.05) increases in plasma luteinizing hormone (LH) concentrations following LHRH administration, which peaked at 5 min post injection and declined thereafter. Plasma testosterone levels increased soon after the LHRH injection in control males, secondary to elevated LH levels in the peripheral circulation, and continued to increase throughout the experimental period. In contrast, this LH-induced elevation in plasma testosterone was delayed in aflatoxin-treated males, with no substantial increase until 20 min post-LHRH injection. In a subsequent experiment, castration of aflatoxin-fed males resulted in an altered response to exogenous LHRH, as compared to their intact counterparts. Based on these data, it appeared that while the LH-secretory capacity of the anterior pituitary was not diminished in birds receiving aflatoxin, the testicular response to exogenous LHRH was altered during aflatoxicosis. Additionally, the effect of castration on plasma LH profiles after LHRH administration provides preliminary evidence for extra-testicular effects of dietary aflatoxin on reproduction in the avian male.


Immunoprophylaxis against rabies.
Rabies is responsible for a large extent of morbidity and mortality in human beings. However, the long incubation period of the disease allows the effective utilization of post exposure immunization. Till recently neural tissue vaccines were the mainstay of antirabic immunoprophylaxis. These vaccines are, associated with severe neuroparalytic complications. The recent introduction of human diploid cell vaccine and chick embro fibroblast vaccines have heralded a new era in antirabic vaccination because of their high immunogenicity and lack of major side effects.


Becoming an effective learner.
The teaching of medicine and the expectations of trainees has changed enormously over the past two decades in parallel to changes in medical technology, advances in information technology and the provision of healthcare. With a shortened time in medical training efficient learning is ever more crucial and the skills with which to optimise and enhance our learning opportunities are discussed.


The genetics of idiopathic hypogonadotropic hypogonadism:unraveling the biology of human sexual development.
Idiopathic Hypogonadotropic Hypogonadism (IHH), a syndrome of GnRH deficiency, is characterized by varying degrees of sexual development disruption. When associated with anosmia, it is termed Kallmann Syndrome (KS). Although it was identified as a hereditary disorder over half a century ago, only during the last two decades have specific putative IHH genes been revealed, including: KAL1, GnRHR, FGFR1, GPR54, PROK2, PROKR2, FGF8, CHD7, TAC3 and TAC3R. Human mutations have shed light on the molecular control of GnRH neuronal embryogenesis and have elucidated elements critical in sexual development. Furthermore, the newly proposed oligogenic model has challenged the dogma of IHH being a single gene disorder and has heightened appreciation for the functional overlap of distinct signaling systems. This review offers an historical perspective to gene discoveries in IHH, genotype-phenotype correlations, and finally, discussion of the evolving complexity of the new IHH genetic model, no longer simply characterized by Mendelian inheritance.


CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease.
CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia. However, it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction, and in other non-hepato-pancreatico-biliary conditions. This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease. All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included. For malignant disease, a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate. The patients were divided into 4 categories: pancreatic adenocarcinoma (PCa); cholangiocarcinoma (CCa); chronic pancreatitis (CP) and biliary calculous disease (Calc). Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted. Final diagnoses were made of pancreatic adenocarcinoma (PCa, n=73), cholangiocarcinoma (CCa, n=19), ampullary carcinoma (Amp, n=7), neuroendocrine carcinoma (Neu, n=4), duodenal carcinoma (Duo, n=3), chronic pancreatitis (CP, n=115), and biliary calculous disease (Calc, n=27). Median CA19-9 levels (U/ml) were: PCa, 653; CCa, 408; Duo, 403; Calc, 27; CP, 19; Neu, 10.5; Amp, 8 (reference range: 0-37). The CA19-9 levels were significantly greater for malignant than for benign disease, could differentiate PCa from CCa/Duo, and were significantly higher in unresectable than in resectable PCa. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for CA19-9 were 84.9%, 69.7%, 67.7% and 86.1%, respectively. A ROC analysis provided an area under the curve for CA19-9 of 0.871 (0.820-0.922), giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology. Using this cut-off, the sensitivity was 82.1%, while specificity, PPV and NPV improved to 85.9%, 81.3% and 86.5%, respectively. When standard radiology was included (US/CT/MRCP) in the decision process, the results improved to 97.2%, 88.7%, 86.6%, and 97.7%. For benign disease, the CA19-9 correlated directly with the serum bilirubin, but for malignant disease, CA19-9 levels were elevated independent of the bilirubin level. CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology, the diagnostic yield is improved significantly, thus stressing the importance of a multi-disciplinary approach to pancreatobiliary disease.


Tricarboxylic acid cycle activity regulates tomato root growth via effects on secondary cell wall production.
Transgenic tomato (Solanum lycopersicum 'Moneymaker') plants independently expressing fragments of various genes encoding enzymes of the tricarboxylic acid cycle in antisense orientation have previously been characterized as exhibiting altered root growth. In this study, we evaluate the rates of respiration of roots from these lines in addition to determining their total dry weight accumulation. Given that these features were highly correlated, we decided to carry out an evaluation of the cell wall composition in the transformants that revealed a substantial reduction in cellulose. Since the bulk of cellulose is associated with the secondary cell walls in roots, we reasoned that the transformants most likely were deficient in secondary wall cellulose production. Consistent with these findings, cross-sections of the root collar (approximately 15 mm from the junction between root and stem) displayed reduced lignified secondary cell walls for the transformants. In contrast, cell and cell wall patterning displayed no differences in elongating cells close to the root tip. To further characterize the modified cell wall metabolism, we performed feeding experiments in which we incubated excised root tips in [U-(14)C]glucose in the presence or absence of phosphonate inhibitors of the reaction catalyzed by 2-oxoglutarate dehydrogenase. Taken together, the combined results suggest that restriction of root respiration leads to a deficit in secondary cell wall synthesis. These data are discussed in the context of current models of biomass partitioning and plant growth.


[A case of ligation of the left pulmonary artery during total arch replacement for aortic arch aneurysm].
Pulmonary artery embolism is one of the most severe complications that can occur in the perioperative period. We report a case of left pulmonary artery obstruction during total arch replacement, which occurred during cardiopulmonary bypass (CPB) for severely invasive procedures. A 59-year-old male was anesthetized for total arch replacement using a double-lumen endobronchial tube (Bronco-Cath 39 F left) in the supine position. The surgery was performed under deep hypothermic circulatory arrest and CPB. When the CPB was finished and mechanical ventilation was started, PaCO2 was unusually elevated. Furthermore, end-tidal CO2 was decreased and no CO2 was expired from the left side of the double-lumen tube. Left pulmonary embolism was highly suspected and pulmonary artery angiography was performed. As the complete obstruction of the left pulmonary artery was demonstrated, pulmonary artery reconstruction was performed. The reason for the obstruction was the surgical ligation during CPB. The wall of the aneurysm was attached to the left pulmonary artery and when it was removed, the left pulmonary artery was injured. The systemic circulation remained stable, however, despite reports that pulmonary embolism was very dangerous and often caused the patient's death.


A hydrodynamics approach to the evolution of multicellularity: flagellar motility and germ-soma differentiation in volvocalean green algae.
During the unicellular-multicellular transition, there are opportunities and costs associated with larger size. We argue that germ-soma separation evolved to counteract the increasing costs and requirements of larger multicellular colonies. Volvocalean green algae are uniquely suited for studying this transition because they range from unicells to multicellular individuals with germ-soma separation. Because Volvocales need flagellar beating for movement and to avoid sinking, their motility is modeled and analyzed experimentally using standard hydrodynamics. We provide comparative hydrodynamic data of an algal lineage composed of organisms of different sizes and degrees of complexity. In agreement with and extending the insights of Koufopanou, we show that the increase in cell specialization as colony size increases can be explained in terms of increased motility requirements. First, as colony size increases, soma must evolve, the somatic-to-reproductive cell ratio increasing to keep colonies buoyant and motile. Second, increased germ-soma specialization in larger colonies increases motility capabilities because internalization of nonflagellated germ cells decreases colony drag. Third, our analysis yields a limiting maximum size of the volvocalean spheroid that agrees with the sizes of the largest species known. Finally, the different colony designs in Volvocales reflect the trade-offs between reproduction, colony size, and motility.


Glycosphingolipid composition of primary cultured human brain microvascular endothelial cells.
Glycosphingolipid (GSL) antigens have been considered to be involved in the pathogenesis of autoimmune neurologic disorders including multiple sclerosis. To establish the GSL pattern specific for endothelial cells forming blood-brain barrier (BBB), we established a method to yield sufficient quantities of highly purified human brain microvascular endothelial cells (HBMECs) and compared their GSL composition to that of human umbilical cord vein endothelial cells (HUVECs), as the representative of endothelial cells not forming BBB. The major gangliosides were GM3 and sialyl paragloboside (LM1), and the major neutral GSLs were lactosylceramide (LacCer), globotriaosylceramide (Gb3), and globoside (Gb4). Trace amounts of GM1, GD1a, GD1b, GT1b, and sulfoglucuronosyl paragloboside (SGPG) could be detected by the high performance thin layer chromatography-overlay method. SGPG was detected only at a nonconfluent state in an amount almost 1/30 that of in nonconfluent HUVECs. Conversely, GM3 and LM1 increased significantly after confluency. The amount of Gb3 in HBMECs was almost as twice that in HUVECs. The significance of these differences in GSL content between HBMECs and HUVECs and between confluent and nonconfluent states is obscure. It might be related, however, to the defense mechanism at the BBB and to the susceptibility of the central nervous system in some disorders that target cell surface GSL, such as hemolytic uremic syndrome.


Minute level smartphone derived exposure to greenness and consumer wearable derived physical activity in a cohort of US women.
Inconsistent results have been found in the literature on associations of greenness, or vegetation quantity, and physical activity. However, few studies have assessed associations between mobility-based greenness and physical activity from mobile health data from smartphone and wearable devices with fine spatial and temporal resolution. We assessed mobility-based greenness exposure and wearable accelerometer data from participants in the US-based prospective Nurses' Health Study 3 cohort Mobile Health (mHealth) Substudy (2018-2020). We recruited 500 female participants with instructions to wear devices over four 7-day sampling periods equally spaced throughout the year. After restriction criteria there were 337 participants (mean age 36 years) with n = 639,364 unique observations. Normalized Difference Vegetation Index (NDVI) data were derived from 30 m x 30 m Landsat-8 imagery and spatially joined to GPS points recorded every 10 min. Fitbit proprietary algorithms provided physical activity summarized as mean number of steps per minute, which we averaged during the 10-min period following a GPS-based greenness exposure assessment. We utilized Generalized Additive Mixed Models to examine associations (every 10 min) between greenness and physical activity adjusting for neighborhood and individual socioeconomic status, Census region, season, neighborhood walkability, daily mean temperature and precipitation. We assessed effect modification through stratification and interaction models and conducted sensitivity analyses. Mean 10-min step count averaged 7.0 steps (SD 14.9) and greenness (NDVI) averaged 0.3 (SD 0.2). Contrary to our hypotheses, higher greenness exposure was associated non-linearly with lower mean steps per minute after adjusting for confounders. We observed statistically significant effect modification by Census region and season. We utilized objective physical activity data at fine temporal and spatial scales to present novel estimates of the association between mobility-based greenness and step count. We found higher levels of greenness were inversely associated with steps per minute.


On the internal representation of numerical magnitude and physical size.
A nascent idea in the numerical cognition literature--the analogical hypothesis (Pinel, Piazza, Bihan, & Dehaene, 2004)--assumes a common noisy code for the representation of symbolic (e.g., numerals) and nonsymbolic (e.g., numerosity, physical size, luminance) magnitudes. The present work subjected this assumption to various tests from the perspective of General Recognition Theory (GRT; Ashby &Townsend, 1986)--a multidimensional extension of Signal Detection Theory (Green & Swets, 1966). The GRT was applied to the dimensions of numerical magnitude and physical size with the following goals: (a) characterizing the internal representation of these dimensions in the psychological space, and (b) assessing various types of (in)dependence and separability governing the perception of these dimensions. The results revealed various violations of independence and separability with Stroop incongruent, but not with Stroop congruent stimuli. The outcome suggests that there are deep differences in architecture between Stroop congruent and incongruent stimuli that reach well beyond the semantic relationship involved.


The determination of Q192R polymorphism of paraoxonase 1 by using non-toxic substrate p-nitrophenylacetate.
The human serum paraoxonase 1 (PON1) is calcium-dependent esterase and associates with the high density serum lipoproteins. PON1 plays a major role in oxidation of high density lipoprotein and low density lipoprotein and prevention of atherogenesis in coronary heart disease. PON1Q and R allele hydrolyses number of substrates like paraoxon (PO) (diethyl p-nitrophenyl phosphate) and phenylacetate. The aim of the study is to the determination of Q192R polymorphism of PON1 by using non-toxic substrate p-nitrophenylacetate and compares it with the phenotype determined by using PO as substrate. The study group consists of 60 healthy normal patients. Paraoxonase activity was measured using the procedure described by Eckerson (Reference method) and for phenotyping; the ratio of hydrolysis of PO in the presence of 1 M NaCl (salt-stimulated PON1, SALT) to the hydrolysis of phenylacetate (PA) is calculated. In new method (Haagen et al.) arylesterase activity measured using p-nitrophenylacetate and for phenotyping arylesterase, the ratio of inhibition of enzymatic hydrolysis of p-nitrophenylacetate (substrate) by phenyl acetate to non-inhibited hydrolysis of p-nitrophenylacetate (inhibited arylesterase activity (IA-IA0)/non-inhibited arylesterase activity (NIA). It was found that paraoxonase activity is trimodally distributed in both the methods. There is no significant difference in the distribution of PON1 phenotypes of both reference method and new method being frequencies 0.946 and 0.376 respectively and there was no significant difference for phenotypic polymorphism for an individual by both methods (χ(2)= 0.15 and P = 0.9262). The Q192R polymorphism of PON1 by using non-toxic substrate p-nitrophenylacetate showed trimodal distribution of QQ (homozygous), QR (heterozygous), and RR (homozygous) phenotype and it is comparable with reference method. This method can be used for PON1 phenotype in different pathological and complex disease conditions.


Nurses' ethical reasoning and behaviour: a literature review.
Today's healthcare system requires that nurses have strong medical-technical competences and the ability to focus on the ethical dimension of care. For nurses, coping with the ethical dimension of care in practise is very difficult. Often nurses cannot act according to their own personal values and norms. This generates internal moral distress, which has a negative impact on both nurses and patients. The objective of this review is a thorough analysis of the literature about nurses' ethical practise particularly with regard to their processes of ethical reasoning and decision making and implementation of those decisions in practise. We conducted an extensive search of the electronic databases Medline, Embase, Cinahl, and PsycInfo for papers published between January 1988 and September 2008. A broad range of search keywords was used. The 39 selected articles had a quantitative, qualitative, or mixed-method design. Despite the conceptual difficulties that the literature on the ethical practise of nurses suffers, in this review we understand nurses' ethical practise a complex process of reasoning, decision making, and implementation of the decision in practise. The process of decision making is more than a pure cognitive process; it is influenced by personal and contextual factors. The difficulties nurses encounter in their ethical conduct are linked to their difficult work environment. As a result, nurses often capitulate to the decisions made by others, which results in a conformist way of acting and less individually adapted care. This review provides us with a more nuanced understanding of the way nurses reason and act in ethically difficult situations than emerged previously. If we want to support nurses in their ethical care and if we want to help them to change their conformist practises, more research is needed. Especially needed are in-depth qualitative studies that explore the experiences of nurses. Such studies could help us better understand not only how nurses reason and behave in practise but also the relationship between these two processes.


[Severe hyponatremia associated with anorexia nervosa: role of inappropriate antidiuretic hormone secretion?].
Anorexia nervosa may be revealed by hyponatremia or associated with it. This hyponatremia can be due to diuretics or laxatives abuse, potomania or inappropriate secretion of antidiuretic hormone as in the case reported here. A 15 year-old girl was admitted for anorexia nervosa. She had secondary amenorrhea and asthenia and had lost 14 kg during the preceding 4 months. Her natremia ranged from 112 to 130 mEq/l with normal urinary sodium excretion, serum hypoosmolality (252 mosm/kg) and inappropriately elevated urinary osmolality (698 mosm/kg). Renal, adrenal and thyroid functions were normal. After water loading, patient remained euvolemic, with a negative free water clearance and an increased plasma ADH level with concomitant hyposmolality. A diagnosis of inappropriate secretion of antidiuretic hormone was made, after excluding other conditions such as potomania, drug abuse, vomiting, tumor and chronic lung disease. Hyponatremia sometimes seen in anorexia nervosa must lead to the search of inappropriate antidiuretic hormone secretion.


Nighttime foraging by deep diving echolocating odontocetes off the Hawaiian islands of Kauai and Ni'ihau as determined by passive acoustic monitors.
Remote autonomous ecological acoustic recorders (EARs) were deployed in deep waters at five locations around the island of Kauai and one in waters off Ni'ihau in the main Hawaiian island chain. The EARs were moored to the bottom at depths between 400 and 800 m. The data acquisition sampling rate was 80 kHz and acoustic signals were recorded for 30 s every 5 min to conserve battery power and disk space. The acoustic data were analyzed with the M3R (Marine Mammal Monitoring on Navy Ranges) software, an energy-ratio-mapping algorithm developed at Oregon State University and custom MATLAB programs. A variety of deep diving odontocetes, including pilot whales, Risso's dolphins, sperm whales, spinner and pan-tropical spotted dolphins, and beaked whales were detected at all sites. Foraging activity typically began to increase after dusk, peaked in the middle of the night and began to decrease toward dawn. Between 70% and 84% of biosonar clicks were detected at night. At present it is not clear why some of the known deep diving species, such as sperm whales and beaked whales, concentrate their foraging efforts at night.


Influence of Epstein-Barr virus infection in adult T-cell leukemia.
The involvement of adult T-cell leukemia (ATL) cells in organs such as the skin and lymph nodes is observed in about 50% of cases of ATL. Epstein-Barr virus (EBV) infection has often been observed in the clinical course of ATL. In this study, we established two B-cell lines from peripheral blood of patients with ATL. EBV DNA, proviral DNA for HTLV-1 and Tax mRNA were detected in both lines. As part of the characterization of these cells, an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) (CD54) or ICAM-3 (ICAM-3) (CD50), lymphocyte function-1 (LFA-1) (CD11a/CD18), and Mac-1 (CD11b/CD18) was observed. To investigate the role of the interaction of these viruses, we transfected EBV and/or HTLV-1 into a healthy donor's lymphocytes, an EBV-infected B cell line, Raji, and a HTLV-1 negative T-cell line, Jurkat. Enhanced expression of adhesion molecules was also observed in double transfectants (EBV and HTLV-1). In the clinical course of ATL, LMP-1, EBNA-2, CD50 and CD54 were detected in lymph nodes and skin specimens by immunohistochemical staining. Furthermore, high levels of interleukin-4 (IL-4) were detected in these cell lines and transfectants. The results indicated that coinfection with HTLV-1 and EBV may induce aggressive organ involvement through the enhanced expression of adhesion molecules via IL-4 signaling. A new mechanism of ATL involvement is discussed.


Migrant workers in the Arab Gulf: the impact of declining oil revenues.
"This article explores the relationship between government expenditure and labor immigration in the Arab Gulf states. This relationship was close and positive during the rapid growth of the 1970s. Using Kuwait as a case study, trends in immigrant labor movements over the period 1981-85 are considered in detail. This analysis shows that the current economic downturn, reflecting the collapse of the world oil prices, has not resulted in the large scale re-export of foreign labor which was envisaged. The reasons for this foreign labor retention are considered and the authors speculate on future migration trends in the region."


MDP25, a novel calcium regulatory protein, mediates hypocotyl cell elongation by destabilizing cortical microtubules in Arabidopsis.
The regulation of hypocotyl elongation is important for plant growth. Microtubules play a crucial role during hypocotyl cell elongation. However, the molecular mechanism underlying this process is not well understood. In this study, we describe a novel Arabidopsis thaliana microtubule-destabilizing protein 25 (MDP25) as a negative regulator of hypocotyl cell elongation. We found that MDP25 directly bound to and destabilized microtubules to enhance microtubule depolymerization in vitro. The seedlings of mdp25 mutant Arabidopsis lines had longer etiolated hypocotyls. In addition, MDP25 overexpression resulted in significant overall shortening of hypocotyl cells, which exhibited destabilized cortical microtubules and abnormal cortical microtubule orientation, suggesting that MDP25 plays a crucial role in the negative regulation of hypocotyl cell elongation. Although MDP25 localized to the plasma membrane under normal conditions, increased calcium levels in cells caused MDP25 to partially dissociate from the plasma membrane and move into the cytosol. Cellular MDP25 bound to and destabilized cortical microtubules, resulting in their reorientation, and subsequently inhibited hypocotyl cell elongation. Our results suggest that MDP25 exerts its function on cortical microtubules by responding to cytoplasmic calcium levels to mediate hypocotyl cell elongation.


Role of BNST CRFR1 Receptors in Incubation of Fentanyl Seeking.
The time-dependent increase in cue-triggered opioid seeking, termed "incubation of opioid craving," is modeled in rodents by examining responding for opioid-associated cues after a period of forced abstinence. With opioid drugs, withdrawal symptoms may heighten cue reactivity by recruiting brain systems involved in both reward seeking and stress responses. Corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) is a critical driver of stress-induced relapse to drug seeking. Here, we sought to determine whether BNST CRF receptor 1 (CRFR1) signaling drives incubation of opioid craving in opioid dependent and non-dependent rats. First, we tested whether BNST CRFR1 signaling drives incubation of opioid craving in rats with short-access fentanyl self-administration experience (2.5 μg/kg/infusion, 3 h/day for 10 days). On Day 1 of forced abstinence, we gave bilateral intra-BNST vehicle injections to all rats and measured lever responding for opioid cues in the absence of fentanyl infusions. On Day 30 of forced abstinence, we gave an identical test after bilateral intra-BNST injections of vehicle or CRFR1 receptor antagonist, R121919 (1 μg/0.3 μL/hemisphere). Vehicle treated rats showed greater responding for opioid associated cues on Day 30 relative to Day 1, and this incubation effect was prevented by intra-BNST R121919 on Day 30. Next, we incorporated an opioid-dependence procedure to investigate whether BNST CRFR1 signaling drives opioid cue-reactivity to a greater extent in opioid-dependent relative to non-dependent rats. We trained rats to self-administer fentanyl for 5 days before initiating the dependence phase and resuming daily fentanyl self-administration sessions for 10 days. We gave intra-BNST R121919 or vehicle injections before testing during acute (Day 5) or protracted (Day 30) withdrawal. During acute withdrawal, antagonizing BNST CRFR1 decreased the number of press bouts without affecting bout size or duration. These patterns of responding with R121919 treatment resulted in less fentanyl-associated conditioned reinforcement during test. Together, these findings suggest a role for BNST CRFR1 signaling in driving cue-reinforced opioid seeking after periods of forced abstinence.