Effects of confinement on anomalies and phase transitions of core-softened fluids.

We use molecular dynamics simulations to study how the confinement affects the dynamic, thermodynamic, and structural properties of a confined anomalous fluid. The fluid is modeled using an effective pair potential derived from the ST4 atomistic model for water. This system exhibits density, structural, and dynamical anomalies, and the vapor-liquid and liquid-liquid critical points similar to the quantities observed in bulk water. The confinement is modeled both by smooth and structured walls. The temperatures of extreme density and diffusion for the confined fluid show a shift to lower values while the pressures move to higher amounts for both smooth and structured confinements. In the case of smooth walls, the critical points and the limit between fluid and amorphous phases show a non-monotonic change in the temperatures and pressures when the nanopore size is increase. In the case of structured walls, the pressures and temperatures of the critical points varies monotonically with the pore size. Our results are explained on basis of the competition between the different length scales of the fluid and the wall-fluid interaction.

[Bisphosphonate-associated osteonecrosis of the jaw]. / Bisphosphonat-assoziierte Kiefernekrosen.

BACKGROUND: Bisphosphonates (BP) are used in the treatment of severe osteoporosis and metastasis of malignant diseases. A possible relationship between the occurrence of osteonecrosis of the jaw and BP therapy was first described in 2003. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is difficult to treat. In some cases the condition of the patients is so compromised that only minimally invasive surgery is possible. Histopathologically, osteonecrosis shows the features of chronic sequestered osteomyelitis, which can be found in different areas of the upper and lower jaw. Sometimes extensive resections of the jaw are necessary. Thus, BRONJ can cause mutilation, impairment of function and esthetics in the orofacial system and, thereby, compromise the life quality of the patients. Triggering factors are often tooth extraction without surgical plastic wound closure of the alveoli, but can also be associated with bruises from denture or other minor wounds. OBJECTIVES: The purpose of this article is to present results from our own patient collective, including therapy regime, success rate, and therapy recommendations. METHODS: The patient populations at three German hospitals were analyzed using a standard questionnaire. The patients in the study group, entered into a follow-up system for early detection of possible BRONJ, were evaluated for treatement outcome. RESULTS: The success rate for prophylactic surgery in asymptomatic patients was very high at 96 %. In the group with symptomatic BRONJ, the outcome was significantly lower (76.4 %). CONCLUSIONS: Because of the complex symptoms, close cooperation between oncologists, dentists, and maxillofacial surgeons is required in the treatment of BRONJ. Before starting therapy with bisphosphonates and during the therapy, dental treatment and monitoring of the patient' oral health is necessary.

Relation between occupation in the first coordination shells and Widom line in core-softened potentials.

Three core-softened families of potentials are checked for the presence of density and diffusion anomalies. These potentials exhibit a repulsive core with a softening region and at larger distances an attractive well. We found that the region in the pressure-temperature phase diagram in which the anomalies are present increases if the slope between the core-softened scale and the attractive part of the potential decreases. The anomalous region also increases if the range of the core-softened or of the attractive part of the potential decreases. We also show that the presence of the density anomaly is consistent with the non-monotonic changes of the radial distribution function at each one of the two scales when temperature and density are varied. Then, using this anomalous behavior of the structure we show that the pressure and the temperature at which the radial distribution function of one of the two length scales equals the radial distribution function of the other length scales identify the Widom line.

Thermodynamic, dynamic, structural, and excess entropy anomalies for core-softened potentials.

Using molecular dynamic simulations, we study three families of continuous core-softened potentials consisting of two length scales: a shoulder scale and an attractive scale. All the families have the same slope between the two length scales but exhibit different potential energy gap between them. For each family three shoulder depths are analyzed. We show that all these systems exhibit a liquid-liquid phase transition between a high density liquid phase and a low density liquid phase ending at a critical point. The critical temperature is the same for all cases suggesting that the critical temperature is only dependent on the slope between the two scales. The critical pressure decreases with the decrease of the potential energy gap between the two scales suggesting that the pressure is responsible for forming the high density liquid. We also show, using the radial distribution function and the excess entropy analysis, that the density, the diffusion, and the structural anomalies are present if particles move from the attractive scale to the shoulder scale with the increase of the temperature indicating that the anomalous behavior depends only in what happens up to the second coordination shell.

Core-softened fluids, water-like anomalies, and the liquid-liquid critical points.

Molecular dynamics simulations are used to examine the relationship between water-like anomalies and the liquid-liquid critical point in a family of model fluids with multi-Gaussian, core-softened pair interactions. The core-softened pair interactions have two length scales, such that the longer length scale associated with a shallow, attractive well is kept constant while the shorter length scale associated with the repulsive shoulder is varied from an inflection point to a minimum of progressively increasing depth. The maximum depth of the shoulder well is chosen so that the resulting potential reproduces the oxygen-oxygen radial distribution function of the ST4 model of water. As the shoulder well depth increases, the pressure required to form the high density liquid decreases and the temperature up to which the high-density liquid is stable increases, resulting in the shift of the liquid-liquid critical point to much lower pressures and higher temperatures. To understand the entropic effects associated with the changes in the interaction potential, the pair correlation entropy is computed to show that the excess entropy anomaly diminishes when the shoulder well depth increases. Excess entropy scaling of diffusivity in this class of fluids is demonstrated, showing that decreasing strength of the excess entropy anomaly with increasing shoulder depth results in the progressive loss of water-like thermodynamic, structural and transport anomalies. Instantaneous normal mode analysis was used to index the overall curvature distribution of the fluid and the fraction of imaginary frequency modes was shown to correlate well with the anomalous behavior of the diffusivity and the pair correlation entropy. The results suggest in the case of core-softened potentials, in addition to the presence of two length scales, energetic, and entropic effects associated with local minima and curvatures of the pair interaction play an important role in determining the presence of water-like anomalies and the liquid-liquid phase transition.

Thermodynamic, dynamic, and structural anomalies for shoulderlike potentials.

Using molecular dynamic simulations we study a family of continuous core-softened potentials consisting of a hard core, a shoulder at closest distances, and an attractive well at further distance. The repulsive shoulder and the well distances represent two length scales. We show that if the first scale, the shoulder, is repulsive or has a small well, the potential has a region in the pressure-temperature phase diagram with density, diffusion, and structural anomalies. However, if the closest scale becomes a deep well, the regions in the pressure-temperature phase diagram where the three anomalies are present shrink and disappear. This result helps in defining two length scales potentials that exhibit anomalies.

[Evaluation of the follow-up of women aged 50-74 years after cervical cytological Ascus abnormalities in cancer screening: adherence to clinical practice guidelines in Isere, France; 1991-2000]. / Evaluation de la prise en charge des femmes de 50 à 74 ans après frottis du col de l'utérus répondu Ascus dans un dépistage organisé en Isère 1991-2000 : application de la conduite à tenir de l'Agence nationale d'accréditation et d'évaluation en santé.

OBJECTIVES: The aim of this study is to compare to the guideline (1998 and 2001) the follow-up of Ascus cytological abnormalities among women aged 50-74 years who have participated at the combined breast, cervical and colorectal cancer screening programme from 1991 to 2000 in Isère, France. PATIENTS AND METHODS: The follow-up of 1154 women with Ascus smear was analysed. A woman was defined according follow-up if she have made a colposcopy or biopsy less than four months after one positive smear or if she has repeated three smears: 3-7 months and 10-14 months after the positive smear and 1 year after the last negative smear. RESULTS: The follow-up was according to guidelines for 28.4% of the 1154 women (150 women are unknowns), 58.6% had a follow-up with too long delay and 17.2% had an uncompleted follow-up. The follow-up did not differ before 1998. It did not differ from women age. Women who were treated by gynaecologist (548) had a better follow-up (according: 35.4%) than the women who were treated by a general practitioner (595). DISCUSSION AND CONCLUSION: The follow-up of Ascus cytological abnormalities is not according to guideline. The follow-up in the screening program will be intensified.

Beta-casein gene promoter activity is regulated by the hormone-mediated relief of transcriptional repression and a mammary-gland-specific nuclear factor.

Transcription from the beta-casein milk protein gene promoter is induced by the synergistic action of glucocorticoid and prolactin hormones in the murine mammary epithelial cell line, HC11. We analyzed the binding of nuclear proteins to the promoter and determined their binding sites. Site-directed mutagenesis was used to determine the function of nuclear factor binding. During lactogenic hormone induction of HC11 cells, the binding of two nuclear factors increased. The binding of two other nuclear factors, present in uninduced cells, decreased. The basal activity of the promoter could be increased to and above the level of the induced wild-type promoter when the recognition sequences of the negatively regulated factors were mutated. This suggests that the beta-casein promoter is regulated by the relief of the repression of transcription. An essential tissue-specific factor was also found in nuclear extracts from the mammary glands of mice. Mutation of its recognition sequence in the beta-casein promoter led to the abolition of the induction of transcription by lactogenic hormones. The DNA sequences recognized by all five of these nuclear factors are conserved in the promoters of different casein genes from several species, confirming their importance in the regulation of milk protein gene transcription.

Systematic review: pre- and post-operative prognostic value of cardiopulmonary exercise testing in liver transplant candidates.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is the gold standard for the objective assessment of functional status. In many conditions, CPET outperforms the traditional variables in predicting mortality. AIM: In patients with cirrhosis listed for liver transplantation, our primary aim was to determine the prognostic value of CPET for pre-and post-transplant mortality and, in particular, whether CPET remained predictive after adjustment for liver disease severity. METHODS: A systematic literature review was conducted in databases Medline, Scopus, Embase and PubMed. Where possible, data were pooled for meta-analyses using a DerSimonian and Laird random effects model. RESULTS: A total of seven studies were retrieved, including 1107 patients with a mean MELD of 14.2 (standard deviation 1.6) and peak baseline VO2 of 17.4 mL/kg/min. In all of the studies in which multivariable analysis was performed, CPET variables were independent predictors of pre-transplant mortality (three studies) and post-transplant mortality (four studies). In the three studies where we could aggregate post-transplant mortality data, post-transplant mortality was predicted by AT with a mean difference of 2.0 (95% confidence interval, CI: 0.42-3.59; Z = 2.48, P = 0.01) between survivors and nonsurvivors. The peak VO2 was not significant (0.77 95% CI: -1.36 to 2.90; Z = 0.71, P = 0.48). CONCLUSIONS: Patient's listed for liver transplant have significant functional limitations, with a weighted mean VO2 below the threshold level required for independent living. Although heterogeneity in study designs with respect to timing, CPET variables, and cut-off values precluded the determination of CPET mortality thresholds, the studies support CPET as an objective and independent predictor of pre- and post-transplant mortality.

Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis.

The mammary gland-specific nuclear factor (MGF) is a crucial contributor to the regulation of transcription from the beta-casein gene promoter. The beta-casein gene encodes a major milk protein, which is expressed in mammary epithelial cells during lactation and can be induced by lactogenic hormones in the clonal mammary epithelial cell line HC11. We have investigated the specific DNA-binding activity of MGF in mammary epithelial cells in vivo and in vitro. Comparison of MGF in HC11 cells and mammary gland cells from lactating mice revealed molecules with identical DNA-binding properties. Bandshift and UV cross-linking experiments indicated that MGF in HC11 cells has a higher mol wt than MGF found in mice. Little MGF activity was detected in nuclear extracts from HC11 cells cultured in the absence of lactogenic hormones. Lactogenic hormone treatment of HC11 cells led to a strong induction of MGF activity. The induction of MGF activity as well as utilization of the beta-casein promoter were suppressed when epidermal growth factor was present in the tissue culture medium simultaneously with the lactogenic hormones. In lactating animals, MGF activity is regulated by suckling, milk stasis, and systemic hormone signals. The mammary glands from maximally lactating animals, 16 days postpartum, contain drastically reduced MGF activity after removal of the pups for only 8 h. The down-regulation of MGF by pup withdrawal was slower in early lactation, 6 days postpartum. We also investigated the relative contributions of local signals, generated by milk stasis, and systemic hormone signals to the regulation of MGF activity. The access to one row of mammary glands of lactating mothers was denied to the pups for 24 h. High levels of MGF were found in the accessible mammary glands, and intermediate levels of MGF were found in the inaccessible glands of the same mouse. Very low MGF levels were detected when the pups were removed from the dams for 24 h. We conclude that systemic as well as local signals cooperate in the in vitro regulation of MGF activity.

[Effect of tamoxifen on plasma proteins in diabetes mellitus type 1]. / Efeito do tamoxifeno no perfil das proteínas plasmáticas em condição de diabetes mellitus tipo 1.

PURPOSE: Considering that important scientific advances have been obtained through studies based on experimental Diabetes mellitus, and that tamoxifen action in humans remains unknown, the aim of the present work is to follow the modifications promoted by diabetes and tamoxifen in the electrophoretic profile of plasmatic proteins. METHODS: It was used 27 Wistar female rats (180-250 body weight), randomicaly divided into five groups: C1 (n = 3, received vehicle), C2 (n = 3, no treatment), T (n =5, treated with tamoxifen, 0.3mg/Kg/day), D (n = 8, experimental diabetes by estreptozotocin, 45mg/Kg and DT (n = 8, diabetic treated with tamoxifen). The electrophoresis was accomplished in cellulose acetate. pH 8.6-8.8, TECNOW chamber, and the strains were stained by Ponceau S. The total proteins were determined by the Biuret method (Labtest). Proteinograms were obtained in densitometer BioSystems BTS-235. RESULTS: Albumin decreased progressively in the groups T, D and DT; a1 fraction increased in groups T and DT; a2 fraction increased in groups T and D, including a synergic effect in group DT; a fraction increased in groups T and D; a fraction increased in groups T, D and DT. CONCLUSIONS: The results indicate an acute phase resposta, with synergic effect of tamoxifen and diabetes, suggesting a probable hepatic lesion.

A solution of electromagnetic imaging using pseudoinverse transformation.

A new reconstruction algorithm as applied to electromagnetic imaging is proposed. It is aimed at reconstructing constitutive parameter distributions of infinitely long dielectric cylinders with arbitrary cross section, from the scattered fields they produce. Computer simulations show that the implementation of the pseudoinverse transformation in this algorithm yields excellent results for thin cylinders irradiated by transverse magnetic (TM) waves, even in the presence of realistic uncertainties in the scattered field measurements.

Meta-analysis: oral or enteral nutritional supplementation in cirrhosis.

BACKGROUND: Malnutrition is a common and clinically significant problem in patients with cirrhosis. The impact of nutritional therapy remains unclear. AIM: To provide an up-to-date systematic review and meta-analysis of RCTs of oral or enteral nutritional supplementation (ONS or ENS) on nutritional and clinical outcomes in adult patients with cirrhosis. METHODS: The primary outcome measure was survival. Included: full-text English language RCTs investigating ONS or ENS vs. a standard nonsupplemented diet in patients with cirrhosis. Excluded: parenteral or branched chain amino acids intervention; treatment duration ≤7 days, exclusive evaluation of posttransplant, postsurgical or quality of life outcomes. RESULTS: Six trials (4 ONS/2 ENS) and 470 patients were included with 71% males and median age 53 years. When all studies were combined, there was no reduction in mortality [Relative risk (RR): 0.75 (0.42, 1.32), P = 0.31]. Subgroup analysis of 3 of the 4 ONS studies did demonstrate a mortality reduction [RR: 0.40 (0.18, 0.90), P = 0.03]. Of the 2 ENS studies, one included the sickest patients in the meta-analysis (82% Child Pugh C) and the other had the shortest mean intervention duration (8.6 days), possibly impacting the potential for benefit. Study quality was suboptimal (median Jadad = 2). CONCLUSIONS: Although there is insufficient evidence to definitively state that oro-enteral nutritional supplementation impacts clinical outcomes, on the basis of this analysis, one can be cautiously optimistic that there is the potential for benefit without an increase in adverse events. Adequately powered, Child Pugh stratified studies of at least 1 month in duration are needed to clarify the impact on relevant clinical outcomes.

CHOP/GADD153 gene expression response to cellular stresses inhibited by prior exposure to ultraviolet light wavelength band C (UVC). Inhibitory sequence mediating the UVC response localized to exon 1.

CHOP/GADD153 is both an activating and repressing transcription factor that is markedly induced in response to a variety of cellular stresses. The CHOP/GADD153 gene was originally cloned because of its inducibility by ultraviolet light wavelength band C (UVC) and has since been found to be activated in response to many different cellular stresses. Some of the recent studies have questioned the UVC responsiveness of the CHOP gene. Contradiction in our own data led us to reexamine the UVC effects on CHOP expression. UVC is capable of strongly activating the mouse CHOP promoter in stably transfected NIH 3T3 cells but has only a modest and transient effect on the level of the CHOP messenger RNA. In addition to its positive effect on CHOP promoter activity, we show that UVC negatively affects CHOP mRNA and protein expression. Pretreatment of NIH 3T3 cells with UVC markedly attenuates the subsequent induction of CHOP mRNA by the cellular stress activators methylmethane sulfate, tunicamycin, glucose deprivation, and methionine deprivation for as long as at least 16 h. This inhibitory effect of UVC on CHOP expression in response to stress is independent of the presence or absence of p53 and does not involve mRNA degradation as opposed to the UVC effect that inhibits p21 expression seen only in the absence of p53. The target of the inhibitory effect of UVC on CHOP expression is located in the first exon of the gene, a 5'-untranslated region that is unusually conserved between different species. These findings suggest that an unknown function encoded by the 5'-untranslated region somehow modifies the response of CHOP gene transcription to UVC.