International multidisciplinary expert panel consensus on breast reconstruction and radiotherapy.

BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.

ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.

Open-Label Clinical Trials of Oral Pulse Dexamethasone for Adults with Idiopathic Nephrotic Syndrome.

BACKGROUND: In adults with primary focal segmental glomerulosclerosis (FSGS), daily prednisone may induce complete remissions (CR) and partial remissions (PR), but relapses are frequent and adverse events are common. METHODS: We carried out 2 open-label, uncontrolled trials to explore the efficacy and tolerability of pulse oral dexamethasone as an alternative to daily prednisone. We enrolled adult patients with proteinuria > 3.5 g/day despite the use of renin-angiotensin-aldosterone blockade. In the first trial, we enrolled 14 subjects with FSGS and administered 4 dexamethasone doses (25 mg/m2) daily for 4 days, repeated every 28 days over 32 weeks. The second trial involved a more intensive regimen. Eight subjects received 4 dexamethasone doses of 50 mg/m2 every 4 weeks for 12 weeks, followed by 4 doses of 25 mg/m2 every 4 weeks for 36 weeks; subjects were randomized to 2 doses every 2 weeks or 4 doses every 4 weeks. RESULTS: In the first trial, we enrolled 13 subjects with FSGS and 1 with minimal change disease and found a combined CR and PR rate of 36%. In the second trial, we enrolled 8 subjects. The combined CR and PR rate was 29%. Analysis combining both trials showed a combined CR and PR rate of 33%. Adverse events were observed in 32% of subjects, with mood symptoms being most common. There were no serious adverse events related to the study. CONCLUSION: We conclude that high dose oral dexamethasone is well tolerated by adults with idiopathic nephrotic syndrome and may have some efficacy.

Implementing dimer metadynamics using gromacs.

We develop a Gromacs implementation of dimer metadynamics (DM) (JCTC 13, 425 [2017]) for enhanced sampling through artificial delocalization effects. This implementation is based entirely on a Plumed collective variable developed for this purpose, the fine tuning of Gromacs input parameters, modified forcefields and custom nonbonded interactions. We demonstrate this implementation on alanine dipeptide in vacuum and in water, and on the 12-residue alanine polypeptide in water and compare the results with a standard multiple-replica technique such as parallel tempering. In all the considered cases, this comparison is consistent and the results with DM are smoother and require shorter simulations, thus proving the consistency and effectiveness of this Gromacs implementation. © 2018 Wiley Periodicals, Inc.

Chemical elemental analysis of single acoustic-levitated water droplets by laser-induced breakdown spectroscopy.

Laser-induced breakdown spectroscopy is presented for trace element detection of liquid samples by analyzing a single droplet levitated by ultrasonic waves. A single liquid droplet is placed in the node of a standing acoustic wave produced by a uniaxial levitator for further chemical analysis. The acoustic levitator consists of a commercial Langevin-type transducer, attached to a concave mechanical amplifier, and a concave reflector. A micro-syringe was used to manually place individual liquid droplet samples in the acoustic levitation system. For chemical analysis, a laser-induced plasma is produced by focusing a single laser pulse on the levitated water droplet after it partially dries. The performance of the acoustic levitator on micron-sized droplets is discussed, and the detection of Ba, Cd, Hg, and Pb at parts per million (milligrams/liter) and sub-parts per million levels is reported. The process, starting from placing the sample in the acoustic levitator and ending on the chemical identification of the traces, takes a few minutes. The approach is particularly interesting in applications demanding limited volumes of liquid samples and relative simple and inexpensive techniques.

Quantum Symmetry from Enhanced Sampling Methods.

We address the problem of the minus sign sampling for two-electron systems using the path integral approach. We show that this problem can be reexpressed as one of computing free energy differences and sampling the tails of statistical distributions. Using metadynamics, a realistic problem like that of two electrons confined in a quantum dot can be solved. We believe that this is a strategy that can possibly be extended to more complex systems.

Dietary Habits and Risk of Kidney Function Decline in an Urban Population.

OBJECTIVE: Explore the association between following a Dietary Approaches to Stop Hypertension (DASH)-accordant diet and kidney end points among urban adults. DESIGN: Prospective cohort study. SETTING: Healthy Aging in Neighborhoods of Diversity across the Life Span study. SUBJECTS: A total of 1,534 urban dwelling participants of the Healthy Aging in Neighborhoods of Diversity across the Life Span study with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/minute/1.73 m2. INTERVENTION: DASH diet accordance determined via a score based on nine target nutrients. MAIN OUTCOME MEASURE: Rapid kidney function decline (eGFR decline >3 mL/minute/1.73 m2 per year), incident chronic kidney disease (CKD) (follow-up eGFR <60 mL/minute/1.73 m2), and eGFR decline >25%. RESULTS: Participants' mean age was 48 years, and 59% were African-American. Median DASH score was 1.5 (range, 0-8). Over a median of 5 years, 13.4% experienced rapid eGFR decline, including 15.2% among participants not following a DASH-accordant diet (score ≤1) and 12.0% with higher accordance (score >1) (P = .08). Outcomes varied by hypertension status. In multinomial logistic regression models, following adjustment for sociodemographic and clinical factors, including total energy intake, low DASH diet accordance was associated with rapid eGFR decline among participants with hypertension (risk ratio, 1.68; 95% confidence interval: 1.17-2.42) but not among those without hypertension (risk ratio, 0.83; 95% confidence interval: 0.56-1.24; P interaction .001). There was no statistically significant association between DASH diet accordance and incident CKD or eGFR decline >25%. Results were similar when DASH diet accordance was analyzed in tertiles. CONCLUSIONS: Among urban adults, low accordance to a DASH-type diet was not associated with incident CKD, but was associated with higher risk of rapid eGFR decline among those with hypertension, yet not among those without hypertension. Further study of dietary patterns as a potential target for improving kidney outcomes among high-risk populations is warranted.

Enhanced decolorization of dyes by an iron modified clay and thermodynamic parameters.

The sorption processes of red 5 (R5) and yellow 5 (Y5) dyes by iron modified and sodium bentonite in aqueous solutions was evaluated. The modified clay was prepared, conditioned and characterized. The sodium clay did not remove any of either dye. The sorption kinetics and isotherms of R5 and Y5 dyes by iron modified clay were determined. The maximum removal percentages achieved were 97% and 98% for R5 and Y5, respectively, and a contact time of 72 h; the experimental data were best adjusted to Ho model. The isotherms of both dyes were best adjusted to the Langmuir model and the maximum adsorption capacities of the modified clay were 11.26 mg/g and 5.28 mg/g for R5 and Y5, respectively. These results indicate that adsorption processes have a high probability to be described as chemisorption on a homogeneous material. Temperature range between 283 and 213 K does not affect the adsorption of Y5 by the iron modified clay, but the adsorption process of R5 was affected, and the thermodynamic parameters could be calculated, which indicate a chemisorption mechanism.

Mixing effects in the crystallization of supercooled quantum binary liquids.

By means of Raman spectroscopy of liquid microjets, we have investigated the crystallization process of supercooled quantum liquid mixtures composed of parahydrogen (pH2) or orthodeuterium (oD2) diluted with small amounts of neon. We show that the introduction of the Ne impurities affects the crystallization kinetics in terms of a significant reduction of the measured pH2 and oD2 crystal growth rates, similarly to what found in our previous work on supercooled pH2-oD2 liquid mixtures [Kühnel et al., Phys. Rev. B 89, 180201(R) (2014)]. Our experimental results, in combination with path-integral simulations of the supercooled liquid mixtures, suggest in particular a correlation between the measured growth rates and the ratio of the effective particle sizes originating from quantum delocalization effects. We further show that the crystalline structure of the mixtures is also affected to a large extent by the presence of the Ne impurities, which likely initiate the freezing process through the formation of Ne-rich crystallites.

Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

BACKGROUND: Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items. METHODS: The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed. RESULTS: Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26. CONCLUSION: The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR.

Serum IL-12 is increased in Mexican obese subjects and associated with low-grade inflammation and obesity-related parameters.

Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF- α ), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF- α (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans.

Double-pulse and calibration-free laser-induced breakdown spectroscopy at low-ablative energies.

The use of double-pulse laser-induced breakdown spectroscopy (DP-LIBS) in quantitative analysis generally depends on standards and calibration curves. To our knowledge, in this Letter, we report the first quantitative analysis based on DP-LIBS at low ablative energies with a self-calibrated method. We compare the effects of plasmas on the calibration-free LIBS technique, generated by DP-LIBS, and the traditional single-pulse (SP) LIBS on a steel sample. Our analyses reveal that when SP-LIBS and DP-LIBS reach comparable emission line intensities, plasma parameters and quantitative analysis are practically the same for both experiments. Additionally, we report the behavior of the emission enhancement of some elements (Fe and Cr) at low ablative pulse energies (0.2-8 mJ) using the orthogonal reheating DP-LIBS configuration.

Text mining and word embedding for classification of decision making variables in breast cancer surgery.

INTRODUCTION: Decision making in surgical oncology of the breast has increased its complexity over the last twenty years. This Delphi survey investigates the opinion of an expert panel about the decision making process in surgical procedures on the breast for oncological purposes. METHODS: Twenty-seven experts were invited to partake into a Delphi Survey. At the first round they have been asked to provide a list of features involved in the decision making process (patient's characteristics; disease characteristics; surgical techniques, outcomes) and comment on it. Using text-mining techniques we extracted a list of mono-bi-trigrams potentially representative of decision drivers. A technique of "natural language processing" called Word2vec was used to validate changes to texts using synonyms and plesionyms. Word2Vec was also used to test the semantic relevance of n-grams within a corpus of knowledge made up of books edited by panel members. The final list of variables extracted was submitted to the judgement of the panel for final validation at the second round of the Delphi using closed ended questions. RESULTS: 52 features out of 59 have been approved by the panel. The overall consensus was 87.1% CONCLUSIONS: Text mining and natural language processing allowed the extraction of a number of decision drivers and outcomes as part of the decision making process in surgical oncology on the breast. This result was obtained transforming narrative texts into structured data. The high level of consensus among experts provided validation to this process.

[Pathogenic mechanisms of SARS-CoV-2 infection and kidney disease: a clinical and molecular perspective].

The SARS-CoV-2 infection has become as a worldwide public health emergency. It exhibits a variety of clinical presentations, ranging from benign to acute respiratory distress syndrome, systemic involvement, and multiorganic failure. The severity of the clinical picture depends on host and virus biological features and the presence of comorbidities such as chronic kidney disease. In addition, the interaction between the virus, angiotensin-converting enzyme 2, and the exacerbated immune response could lead to the development of acute kidney injury. However, the implications of SARS-CoV-2 infection on renal cells, the prognosis of patients with chronic kidney disease, and the long-term behavior of renal function are not entirely understood. This review aims to explore the role of SARS-CoV-2 in acute and chronic kidney disease and the possible pathogenic mechanisms of renal involvement.

Effect of Bacillus-direct-fed microbial on leaky gut, serum peptide YY concentration, bone mineralization, and ammonia excretion in neonatal female turkey poults fed with a rye-based diet.

Rye is high in nonstarch polysaccharides (NSP), a complex carbohydrate which cannot be digested by poultry as they lack the endogenous enzymes to do so. Exogenous carbohydrases must therefore be supplemented to avoid the antinutritional effects associated with a high NSP diet. The objectives of the present study were to evaluate the effects of a rye-based diet with and without supplementation of a Bacillus direct-fed microbial (DFM) on body weight, bone mineralization, and leaky gut, as well as its role on influencing serum concentrations of peptide YY (PPY) and the ammonia concentration in turkey manure. Two independent trials were conducted. In each experiment, day-of-hatch female turkey poults were neck tagged and randomly assigned to either a control rye-based diet or a rye-based diet supplemented with the DFM (n = 25 birds/group). At 10 days-of-age, poults in both groups were administered with an appropriate dose of fluorescein isothiocyanate-dextran (FITC-d) by oral gavage. One hour later, all poults were euthanized. Blood was collected to evaluate serum FITC-d and PPY concentrations. Furthermore, in Trial 2 only, both tibias were removed for assessment of bone parameters, and turkey manure was collected to evaluate physicochemical analysis. In both trials, poults treated with the DFM showed a significant increase (P < 0.05) in body weight and body weight gain as compared with control nontreated poults. Poults that received the DFM also had a significant reduction in serum levels of PPY and FITC-d when compared with control nontreated poults. In Trial 2, turkeys treated with the DFM had a substantial increase in tibia strength, tibia diameter, total ash, calcium, and phosphorus when compared with control nontreated turkeys. Their manure was also shown to have a significant reduction in the concentration of ammonia. This is the first report of a commercial DFM reducing the concentration of this compound in turkey manure. In summary, the results of the present study confirm that turkeys fed with a rye-based diet have a significant increase in gut permeability, a reduced body weight, and decreased bone mineralization when compared with turkeys fed with the DFM. Turkeys that received the rye-based diet supplemented with the Bacillus-DFM also had a significant reduction in the serum concentration of PPY when compared with control turkeys. This finding suggests a possible prebiotic effect of rye, warranting future studies to test this effect. Further studies to evaluate the microbiota diversity, as well as the concentration of ceca short-chain fatty acids, are also necessary to confirm the reliability of PPY as a potential metabolomic biomarker in poultry.

Exact ground state Monte Carlo method for Bosons without importance sampling.

Generally "exact" quantum Monte Carlo computations for the ground state of many bosons make use of importance sampling. The importance sampling is based either on a guiding function or on an initial variational wave function. Here we investigate the need of importance sampling in the case of path integral ground state (PIGS) Monte Carlo. PIGS is based on a discrete imaginary time evolution of an initial wave function with a nonzero overlap with the ground state, which gives rise to a discrete path which is sampled via a Metropolis-like algorithm. In principle the exact ground state is reached in the limit of an infinite imaginary time evolution, but actual computations are based on finite time evolutions and the question is whether such computations give unbiased exact results. We have studied bulk liquid and solid (4)He with PIGS by considering as initial wave function a constant, i.e., the ground state of an ideal Bose gas. This implies that the evolution toward the ground state is driven only by the imaginary time propagator, i.e., there is no importance sampling. For both phases we obtain results converging to those obtained by considering the best available variational wave function (the shadow wave function) as initial wave function. Moreover we obtain the same results even by considering wave functions with the wrong correlations, for instance, a wave function of a strongly localized Einstein crystal for the liquid phase. This convergence is true not only for diagonal properties such as the energy, the radial distribution function, and the static structure factor, but also for off-diagonal ones, such as the one-body density matrix. This robustness of PIGS can be traced back to the fact that the chosen initial wave function acts only at the beginning of the path without affecting the imaginary time propagator. From this analysis we conclude that zero temperature PIGS calculations can be as unbiased as those of finite temperature path integral Monte Carlo. On the other hand, a judicious choice of the initial wave function greatly improves the rate of convergence to the exact results.

De-escalation of complexity in oncoplastic breast surgery: Case series from a specialized breast center.

INTRODUCTION: Oncoplastic breast surgery has evolved the surgical treatment of breast cancer over the past two decades. This practice still lacks validation and poses several dilemmas in terms of safety, local and systemic control, timing of adjuvant treatments and cost-effectiveness. Our case series investigates the effects of a reduced surgical complexity on cosmetic results and quality of life. METHODS: We treated 76 consecutive patients affected by early stage breast cancer from January 2016 to April 2017. We employed a decision support system to assist the final shared decision making. The communication process before surgery included new specific information on recent evidence about local control of disease and outcomes after multimodality treatment. In order to estimate the oncoplastic complexity, we created a new score based on scars, bilateral procedures and type and timing of reconstructions. We compared the outcomes of this series to that of a previous one from the same institution. RESULTS: The medium complexity score (CS) in the current series was significantly lower compared to that of the previous series (medium CS cohort 1 = 3.1 vs medium CS cohort 2 = 1.51; p = 0.001). Complications according to Clavien-Dindo classification did not vary significantly between the two series (p = 0.7). The increased use of primary systemic treatment did not translate into a significantly lower mastectomy rate (cohort 1 = 20% vs cohort 2 = 16%; p = n.s.). There was no significant difference in breast deformities after breast conserving surgery (p = 0.2). The BCCT.Core demonstrated a 67.1% occurrence of "good" results. Quality of life in patients who underwent breast-conserving surgery measured using the Breast-Q demonstrated similar results in the pre-post-op assessment. CONCLUSIONS: This study hypothesizes that a proper information may impact on patient's decisions and may reduce surgical complexity. This reduction likely has no effects on the main surgical outcomes estimated using standard tools. More investigations should be performed on a larger multi-institutional scale to confirm these conclusions.

Evaluation of in ovo Bacillus spp. based probiotic administration on horizontal transmission of virulent Escherichia coli in neonatal broiler chickens.

This study evaluated the effect of in ovo Bacillus spp. base probiotic (BBP) administration on hatchability, Gram-negative bacteria (GNB) recovery, performance, and microbiota composition in 2 independent trials using a virulent E. coli seeder challenge model. In each trial, one hundred and eighty 18-day-old embryos were allocated into 1 of 2 groups: Control and treated group (inoculated with 107 BBP). On day 19 of embryogenesis, seeder embryos (n = 18) were inoculated with 4.5 × 104E. coli/mL+272 µg/mL tetracycline and segregated into mesh hatching bags. Twelve chicks per group were euthanized at hatch and at day 7 to evaluate the gastrointestinal composition of total GNB or total aerobic pasteurized bacteria. Also, in trial 2, ceca content from five chickens at day 7 were collected to evaluate microbiota composition. Embryos inoculated with BBP showed a significant (P < 0.05) reduction in the total number of GNB at day-of-hatch (DOH) and day 7. Probiotic treatment increased BW at DOH and day 7, and BW gain (days 0 to 7) when compared with Control chickens. Proteobacteria phylum was significantly reduced, while the Firmicutes was significantly increased by the BBP as compared to the Control (P < 0.05). At family level, Enterobacteriaceae was significantly decreased, while the Lachnospiraceae was significantly elevated in the BBP as compared to the Control group (P < 0.05). The genus Oscillospira was significantly enriched in the BBP group, whereas the unidentified genus of family Enterobacteriaceae in the Control group (P < 0.05). The BBP group increased the bacterial species richness, although there was no significant difference between treatments (P > 0.05). Interestingly, beta diversity showed a significant difference in bacterial community structure between Control and BBP groups (P < 0.05). The results of the present study suggest that in ovo administration of a BBP can reduce the severity of virulent E. coli horizontal transmission and infection of broiler chickens during hatch. The reduction in the severity of the transmission and infection by the BPP might be achieved through alterations of microbiota composition and its community structure.

Enhanced levels of oxidized low-density lipoprotein prime monocytes to cytokine overproduction via upregulation of CD14 and toll-like receptor 4 in unstable angina.

OBJECTIVES: The purpose of this study was to establish whether oxidized low-density lipoprotein (oxLDL) contributes to cytokine overproduction via upregulation of CD14 and toll-like receptor-4 (TLR-4) expression on circulating monocytes of unstable angina (UA) patients. METHODS AND RESULTS: Expression of CD14 and TLR-4 on circulating monocytes, and the concentration of plasma oxLDL, (interleukin [IL])-6, IL-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1) were measured in 27 control (C) subjects, 29 patients with stable angina (SA), and 27 with UA. CD14 and TLR-4 expression on monocytes and circulating IL-6, IL-1 beta, and oxLDL were higher in UA than in SA and C subjects (P<0.001). In in vitro experiments, oxLDL increased CD14 and TLR-4 expression (P<0.001) in control monocytes as well as IL-6, IL-1 beta, and at a lower extent TNF-alpha and MCP-1 levels in the supernatant (P from <0.05 to <0.001). The preincubation of sera derived from UA patients but with control monocytes also induced a significant increase of CD14 and TLR-4 expression (P<0.001) and of IL-6 and IL-1 beta production (P<0.001) in the supernatant. CONCLUSIONS: In UA patients oxLDL may contribute to monocyte overproduction of some cytokines by upregulating CD14 and TLR-4 expression.

Reduction of capsular thickness around silicone breast implants by zafirlukast in rats.

Capsular contracture is a very disappointing complication, with an overall incidence between 0.5 and 30% of breast implant operations and, if severe, requiring a further surgical procedure (capsulotomy or capsulectomy). Many frustrating attempts have been made to prevent the fibrotic reaction, mainly with steroids or antibiotics. More recently leukotriene antagonists clinically used in the asthma and lung diseases have been suggested to be potentially useful in counteracting the inflammatory pathway leading to a dense collagen membrane around the prosthesis and thus preventing contracture of the capsule. In this study we evaluated the effectiveness of zafirlukast with the following protocol. Disks of textured implant material were placed dorsally into each of the subcutaneous tissues of 40 rats that were subdivided in 2 groups: 20 rats treated with zafirlukast and 20 controls. At autopsy 77 days after, each implant with its surrounding collagenic tissue was excised, and the macroscopic measure of the membrane thickness was compared with the pathology reports, to definitely assess the foreign body reaction. The mean total thickness of the capsule around the implants was 161.97 microm in the zafirlukast-treated group compared with 345.98 microm in the control group (p < 0.001). Outstandingly, the collagen fibers and fibroblast layer were reduced in the zafirlukast-treated group compared to the controls. Our study confirms the effectiveness of this compound in preventing fibrosis and putatively also in reducing the extent of collagen reaction when a capsule has been formed.

Synthesis of fluorescent dendrimers with an oligo(phenylenevinylene) core.

Novel fluorescent dendrimers of first, second, and third generation bearing a conjugated oligo(phenylenevinylene) (OPV) core and peripherial allyl chains as dendrons have been synthesized by a convergent method. The compounds have been fully characterized by 1H, 13C NMR, FTIR, UV-vis, and fluorescence spectroscopy, MALDI-TOF or FAB+ mass spectroscopy and elemental analysis. All dendrimers showed in solution a blue fluorescence with a maximum wavelength at 444-446 nm and can be deposited as thin films emitting in the blue-green region. The most homogeneous films were obtained for the second generation dendrimer which also exhibits the higher quantum yield in solution. These properties make it a possible candidate for application in organic light emitting diodes (OLEDs).