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1.
Actas Dermosifiliogr ; 2024 Sep 11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39271008

RESUMO

INTRODUCTION: Clinical trials have validated the use of nivolumab and pembrolizumab as adjuvant therapies regarding relapse-free survival in patients with resected stage III and IV melanoma. Evidence in real-world patients is currently limited. MATERIAL AND METHOD: The CADIM trial (Characterization of adjuvant immunotherapy in melanoma patients) recruited a total of 81 patients with resected stage III and IV melanoma on nivolumab or pembrolizumab as adjuvant therapy from February 2018 through December 2022. RESULTS: The stage distribution rate was 81.5% (n=71) for stage III, while 15 patients (18.5%) had resected stage IV. Among stage III patients, 38 were stage IIIC (46.9%). With a median follow-up of 22.8 months, the relapse-free survival in the intention-to-treat population was 84% at one year and 81.5% at 2 years. The overall survival rate was 99% at one year and 91.4% at 2 years. Grade 3-4 treatment-related adverse events were reported in 12.3% of the patients. CONCLUSIONS: This study shows the results of resected stage III and IV melanoma patients on adjuvant therapy with anti-PD-1, and eventually confirmed the safety and efficacy profile described by clinical trials. Comparing clinical trial data with real-world evidence is necessary for a more practical, reliable, and accessible use of these drugs.

2.
Analyst ; 145(17): 5905-5914, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32830828

RESUMO

Lateral flow assays may be used by minimally trained personnel for fast and inexpensive bioanalyses in decentralized non-exigent environments. Their extension to a broader catalog of applications depends on improvements in their quantification and their sensitivity. We report a strategy that combines nanomagnetic tagging of the analyte of interest with radiofrequency inductive sensing, easy to achieve in friendly and portable format. To optimize nanotag performance, we investigated the influences of their magnetic core size and agglomeration. Iron oxide nanoparticles, with sizes from 5 to 23 nm, were synthesized by thermal decomposition and then coated with dimercaptosuccinic acid and functionalized with neutravidin protein. We tested the system by immobilizing biotin in lateral flow membrane strips. When a sample containing the particles flows along the membrane, the biotin captures the neutravidin together with the magnetic nanotags, which are detected by the inductive sensor. The optimal nanotag core size is the critical threshold for superparamagnetic behavior, which maximizes both the initial magnetic permeability and the saturation magnetization. Controlled agglomeration of the nanotags increases the magnetic mass captured in the test line and further amplifies the signal.

3.
J Exp Bot ; 67(9): 2565-72, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27025221

RESUMO

Differentiation and morphogenetic processes during plant development are particularly robust. At the cellular level, however, plants also show great plasticity in response to environmental conditions, and can even reverse apparently terminal differentiated states with remarkable ease. Can we understand and predict both robust and plastic systemic responses as a general consequence of the non-trivial interplay between intracellular regulatory networks, extrinsic environmental signalling, and tissue-level mechanical constraints? Flower development has become an ideal model system to study these general questions of developmental biology, which are especially relevant to understanding stem cell patterning in plants, animals, and human disease. Decades of detailed study of molecular developmental genetics, as well as novel experimental techniques for in vivo assays in both wild-type and mutant plants, enable the postulation and testing of experimentally grounded mathematical and computational network dynamical models. Research in our group aims to explain the emergence of robust transitions that occur at the shoot apical meristem, as well as flower development, as the result of the collective action of key molecular components in regulatory networks subjected to intra-organismal signalling and extracellular constraints. Here we present a brief overview of recent work from our group, and that of others, focusing on the use of simple dynamical models to address cell-fate specification and cell-state stochastic dynamics during flowering transition and cell-state transitions at the shoot apical meristem of Arabidopsis thaliana. We also focus on how our work fits within the general field of plant developmental modelling, which is being developed by many others.


Assuntos
Flores/crescimento & desenvolvimento , Flores/anatomia & histologia , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Meristema/anatomia & histologia , Meristema/crescimento & desenvolvimento , Meristema/fisiologia , Modelos Biológicos , Brotos de Planta/anatomia & histologia , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/fisiologia
4.
Nanotechnology ; 24(24): 245501, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23680874

RESUMO

A novel method for superparamagnetic nanoparticle detection using copper impedance as the sensing property is presented. The increase of impedance produced by the proximity of the nanoparticles in the copper is comparable to that of classical magnetoimpeditive materials. A physical interpretation of the detection in terms of the induction of eddy currents in the copper element by the oscillating magnetic moments of the particles is proposed. Experimental research has been done to support this hypothesis, namely, analyses of the influence of the driving current frequency and amplitude, and of the geometry and size of the sensing conductor. The ability of copper to quantify the number of nanoparticles was successfully verified, evidencing the great potential of this new method.

5.
J Chem Phys ; 137(3): 034502, 2012 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-22830706

RESUMO

Broadband dielectric spectroscopy spanning frequencies from 10(-2) to 1.9 × 10(9) Hz has been used to study the molecular orientational dynamics of the glass-forming liquid crystal 1",7"-bis (4-cyanobiphenyl-4'-yl)heptane (CB7CB) over a wide temperature range of the twist-bend nematic phase. In such a mesophase two different relaxation processes have been observed, as expected theoretically, to contribute to the imaginary part of the complex dielectric permittivity. For measurements on aligned samples, the processes contribute to the dielectric response to different extents depending on the orientation of the alignment axis (parallel or perpendicular) with respect to the probing electric field direction. The low-frequency relaxation mode (denoted by µ(1)) is attributed to a flip-flop motion of the dipolar groups parallel to the director. The high-frequency relaxation mode (denoted by µ(2)) is associated with precessional motions of the dipolar groups about the director. The µ(1)-and µ(2)-modes are predominant in the parallel and perpendicular alignments, respectively. Relaxation times for both modes in the different alignments have been obtained over a wide temperature range down to near the glass transition temperature. Different analytic functions used to characterize the temperature dependence of the relaxation times of the two modes are considered. Among them, the critical-like description via the dynamic scaling model seems to give not only quite good numerical fittings, but also provides a consistent physical picture of the orientational dynamics on approaching the glass transition.

6.
J Chem Phys ; 134(14): 144505, 2011 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-21495762

RESUMO

Recently, Nielsen et al. [J. Chem. Phys. 130, 154508 (2009); Philos. Mag. 88, 4101 (2008)] demonstrated a universal pattern for the high frequency wing of the loss curve for primary relaxation time on approaching the glass transition for organic liquids. In this contribution it is presented that a similar universality occurs for glass-forming liquid crystals and orientationally disordered crystals (plastic crystals). Empirical correlations of the found behavior are also briefly discussed.

7.
J Chem Phys ; 134(2): 024512, 2011 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-21241125

RESUMO

For decades the Vogel-Fulcher-Tammann equation has dominated the description of dynamics of the non-Arrhenius behavior in glass forming systems. Recently, this dominance has been questioned. Hecksher et al. [Nat. Phys. 4, 737 (2008)], Elmatad et al. [J. Phys. Chem. B 113, 5563 (2009)], and Mauro et al. [Proc. Natl. Acad. Sci. U.S.A. 106, 19780 (2009)] indicated superiority of several equations showing no divergence at a finite (nonzero) temperature. This paper shows distortion-sensitive and derivative based empirical analysis of the validity of leading equations for portraying the previtreous evolution of primary relaxation time.

8.
Clin Transl Oncol ; 23(5): 961-968, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33515422

RESUMO

Despite remarkable advances in the knowledge of molecular biology and treatment, ovarian cancer remains the leading cause of death from gynecologic cancer. In the last decade, there have been important advances both in systemic and surgical treatment. However, there is no doubt that the incorporation of PARP inhibitors as maintenance after the response to platinum-based chemotherapy, first in recurrent disease and recently also in first line, will change the natural history of the disease.The objective of this guide is to summarize the current evidence for the diagnosis, treatment, and follow-up of ovarian cancer, and to provide evidence-based recommendations for clinical practice.


Assuntos
Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante/métodos , Ensaios Clínicos Fase III como Assunto , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Oncologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sociedades Médicas , Espanha
9.
Surg Oncol ; 36: 115-119, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33341606

RESUMO

PURPOSE: The objective of this work was to analyze the long-term prevalence of urinary and fecal incontinence and their impact on quality of life in patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (CRS + HIPEC). METHODS: This cross-sectional study included a series of patients with advanced and recurrent ovarian cancer treated by CRS + HIPEC, with a disease-free period of at least 12 months after the procedure. Urinary incontinence was evaluated using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), fecal incontinence using the Wexner test and the Fecal Incontinence Quality of Life (FIQL) questionnaire and global quality of life using the Short Form 36 (SF-36) survey. RESULTS: A total of 64 patients were included in the study, with a median age of 55 years (range 28-78). The urinary incontinence rate was 45% and the fecal incontinence rate was 20%. Up to 14% of the patients presented both types of incontinence. The presence of urinary or fecal incontinence generated a significant negative impact on quality of life in relation to patients without incontinence. DISCUSSION: Urinary and fecal incontinence is frequent in the follow-up of ovarian cancer patients treated with CRS + HIPEC. Reconsidering the approach to the pelvis without peritoneal metastases in the peritoneum could modify the incidence of these pelvic floor dysfunctions.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Incontinência Fecal/patologia , Hipertermia Induzida/efeitos adversos , Neoplasias Ovarianas/terapia , Qualidade de Vida , Incontinência Urinária de Urgência/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Estudos Transversais , Incontinência Fecal/etiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Prognóstico , Incontinência Urinária de Urgência/etiologia
10.
J Chem Phys ; 132(16): 164516, 2010 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-20441297

RESUMO

The alpha-relaxation dynamics of 1-cyano-adamantane (CNA) and its mixtures with 1-chloro-adamantane (ClA) has been studied by means of broadband dielectric spectroscopy. The existence of orientationally disordered (OD) face centered cubic mixed crystals (ClA(1-X)CNA(X)) for 0.5 < or = X < or = 1 has been put in evidence by thermodynamics and structural analyses. In addition to the OD phase of CNA, mixed crystals with compositions higher than the equimolar one exhibit a freezing of the orientational degrees of freedom into a glassy state, which involves also a strong increase of the antiferroelectric order at temperatures higher than the dielectric glass transition temperature. This experimental evidence is revealed by a stairlike effect in the variation of the Kirkwood factor with the temperature as a consequence of a twin effect in the dielectric strength without any anomaly in the temperature-density curves. The characteristic relaxation times are analyzed as a function of temperature and mole fraction. By setting a common temporal origin ("isochronal origin") at tau(T(g)) = 100 s for each mole fraction, it emerges that the substitution of ClA molecules by those of CNA (diminution of X) gives rise to a slow down in the dynamics, despite that the molecular volume of ClA molecules are smaller than those of CNA. This fact goes along and is accompanied by a diminution of the lattice packing with the decrease of composition. It is also shown that the heterogeneities produced by the concentration fluctuations due to the chemical disorder are the main contribution to the non-exponential character of the alpha-relaxation peaks.

11.
Hernia ; 24(2): 257-263, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31069579

RESUMO

BACKGROUND: The incidence of incisional hernia in patients with peritoneal surface malignancies treated by cytoreduction plus hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear, and the criteria commonly used to indicate their repair cannot be applied in these patients. The objective of this work was to analyze the incidence of incisional hernias in these patients, identify the risk factors associated with their appearance, and propose an algorithm for their management. METHODS: We analyzed a series of patients with malignant pathologies of the peritoneal surface treated by cytoreduction with peritonectomy and HIPEC procedures between January 2008 and June 2017. Only patients with a minimum postoperative follow-up period of 12 months were included. RESULTS: Our series included 282 patients, 28 (10%) of whom developed an incisional hernia during the follow-up period. Fifty-one patients, all with ovarian cancer with peritoneal dissemination, did not receive HIPEC after cytoreduction as they were part of the control arm of the CARCINOHIPEC clinical trial (NCT02328716) or because they did not provide specific informed consent. In the multivariate analysis, treatment with HIPEC (OR 2.56, 95% CI [1.57, 4.31], p = 0.032) and the administration of preoperative systemic chemotherapy (OR = 1.59, 95% CI [1.26, 3.58], p = 0.041) were found to be independent factors related to the appearance of an incisional hernia. CONCLUSIONS: The incidence of incisional hernia after cytoreduction and HIPEC is within the ranges described in the literature for other abdominal surgery procedures. The use of systemic chemotherapy and treatment with HIPEC, in particular, were identified as factors related to their occurrence.


Assuntos
Antineoplásicos/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Hérnia Incisional/epidemiologia , Neoplasias Peritoneais/cirurgia , Adolescente , Adulto , Idoso , Algoritmos , Antineoplásicos/administração & dosagem , Feminino , Herniorrafia , Humanos , Incidência , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Peritônio/patologia , Peritônio/cirurgia , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Adulto Jovem
12.
Science ; 288(5467): 859-63, 2000 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-10797009

RESUMO

Light signals perceived by the phytochrome family of sensory photoreceptors are transduced to photoresponsive genes by an unknown mechanism. Here, we show that the basic helix-loop-helix transcription factor PIF3 binds specifically to a G-box DNA-sequence motif present in various light-regulated gene promoters, and that phytochrome B binds reversibly to G-box-bound PIF3 specifically upon light-triggered conversion of the photoreceptor to its biologically active conformer. We suggest that the phytochromes may function as integral light-switchable components of transcriptional regulator complexes, permitting continuous and immediate sensing of changes in this environmental signal directly at target gene promoters.


Assuntos
Proteínas de Arabidopsis , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Luz , Células Fotorreceptoras , Fitocromo/metabolismo , Proteínas de Plantas , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proteínas de Ciclo Celular/genética , DNA de Plantas/genética , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Genes de Plantas , Sequências Hélice-Alça-Hélice , Modelos Genéticos , Oligodesoxirribonucleotídeos/genética , Oligodesoxirribonucleotídeos/metabolismo , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Fitocromo B , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética
13.
J Chem Phys ; 131(18): 184504, 2009 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-19916609

RESUMO

The evolution of the primary relaxation time of orientationally disordered (OD) mixed crystals [(CH(3))(2)C(CH(2)OH)(2)](1-X)[(CH(3))C(CH(2)OH)(3)](X), with 0 < X < or = 0.5, on approaching the glass temperature (T(g)) is discussed. The application of the distortion-sensitive, derivative-based procedure revealed a limited adequacy of the Vogel-Fulcher-Tammann parametrization and a superiority of the critical-like description tau proportional to (T - T(C))(-phi(') ), phi(') = 9-11.5, and T(C) approximately T(g) - 10 K. Basing on these results as well as that of Drozd-Rzoska et al. [J. Chem. Phys. 129, 184509 (2008)] the question arises whether such behavior may be suggested as the optimal universal pattern for dynamics in vitrifying OD crystals (plastic crystals). The obtained behavior is in fair agreement with the dynamic scaling model (DSM) [R. H. Colby, Phys. Rev. E 61, 1783 (2000)], originally proposed for vitrifying molecular liquids and polymers. The application of DSM made it possible to estimate the size of the cooperatively rearranging regions ("heterogeneities") in OD phases near T(g).

14.
Anim Reprod Sci ; 98(3-4): 225-32, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16621353

RESUMO

An experiment was conducted to ascertain if follicles could reach ovulatory size after the largest follicle (dominant) has been removed at different times during a progestin treatment in anestrous ewes, and secondly to determine if these new follicles could respond to an hCG-induced ovulation and have similar function as corpora lutea. Mature crossbred sheep (n=44) in anestrous were treated with an intravaginal sponge containing 40 mg of FGA (day 0=sponge insertion) for 9 days. Treatments consisted of cauterization of the largest follicle on the experimental day 3 (T1), day 6 (T2) and day 9 (T3); day 12 to ascertain the size of the largest follicle in control ewes. During laparotomies, the diameters of the largest follicle (DF), and those of the second and third largest follicles (SF1 and SF2, respectively) were determined. On day 12, a second laparotomy was performed for those ewes which had their DF cauterized on days 3, 6 and 9, a fourth group was left intact and only laparotomized on day 12. At this time, the size of the new DF, SF1 and SF2 were determined. Immediately after the laparotomy on day 12, all the ewes were treated with 1000 i.u. of hCG to induce ovulation. Blood samples were collected daily from day 0 to 50 and samples were analyzed for progesterone concentrations. The size of the DF at the time of sponge removal was smaller that those observed on day 3 or 6 of sponge suggesting that follicles in ewes treated with this progestin regress and a new wave of follicular development ensues between day 6 and the time of sponge removal. The size of the DF on day 12 was also smaller in ewes that have the largest follicle removed at the time of sponge removal reflecting that these follicles had a shorter period of growth; however, the rate of growth was greater for these follicles than for follicles arising after cauterization on day 3 or 6 after sponge insertion. There were no differences among treatments, in the number of ewes that formed a corpus luteum (CL) in response to hCG. Life span of the corpora lutea did not differ among ewes having their DF removed on day 6 or 9 or those that served as controls, however, ewes that had their DF removed on day 3 developed longer lived CL in a larger proportion of animals. Average progesterone concentration during the life span of the induced corpora lutea was greater in control ewes than in any other experimental group. These observations allow us to conclude that, (a) the follicular dynamics observed in anestrous ewes treated with a progestin intravaginal sponge resembles that observed during the normal estrous cycle in the ewe; (b) the effects of progesterone on life span of the corpus luteum could not be only related to direct effects at the follicle but also involve changes in other components of the uterine-ovarian-hypothalamic axis; (c) the mechanisms controlling luteal life span seem to be different to those mechanisms controlling the function of the induced corpus luteum.


Assuntos
Anestro/efeitos dos fármacos , Cauterização/veterinária , Folículo Ovariano/fisiologia , Ovinos/fisiologia , Animais , Corpo Lúteo/fisiologia , Feminino , Acetato de Fluorogestona/farmacologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/cirurgia , Ovário/efeitos dos fármacos , Ovário/fisiologia
15.
Clin Transl Oncol ; 19(3): 386-395, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27525978

RESUMO

PURPOSE: The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. METHODS: We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. RESULTS: 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. CONCLUSION: Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.


Assuntos
Neutropenia Febril/etiologia , Neutropenia Febril/patologia , Infecções/complicações , Neoplasias/complicações , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
16.
Nanoscale ; 8(27): 13321-32, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27341001

RESUMO

We propose a new methodology based on lock-in thermography to study and quantify the heating power of magnetic nanoparticles. Superparamagnetic iron oxide nanoparticles exposed to a modulated alternating magnetic field were used as model materials to demonstrate the potency of the system. Both quantitative and qualitative information on their respective heating power was extracted at high thermal resolutions under increasingly complex conditions, including nanoparticles in the liquid, solid and aggregated states. Compared to conventional techniques, this approach offers a fast, sensitive and non-intrusive alternative to investigate multiple and dilute specimens simultaneously, which is essential for optimizing and accelerating screening procedures and comparative studies.

17.
Methods Mol Biol ; 1284: 455-79, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25757787

RESUMO

Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.


Assuntos
Redes Reguladoras de Genes , Genômica , Modelos Teóricos , Desenvolvimento Vegetal/genética , Arabidopsis/genética , Biologia Computacional/métodos , Genômica/métodos , Raízes de Plantas/genética , Software
18.
Front Microbiol ; 6: 221, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25852677

RESUMO

Between September and October of 2004, more than 1230 cases of gastroenteritis due to pandemic O3:K6 strains of Vibrio parahaemolyticus (V. parahaemolyticus) were reported in the relatively small geographical area of Southern Sinaloa, a state located in Northwest Mexico. Since then, V. parahaemolyticus-associated gastroenteritis cases have gradually increased in prevalence spreading from south to north. The present study conducted an epidemiological surveillance of V. parahaemolyticus strains in both environmental and clinical samples along the Pacific coast of Sinaloa from 2011 to 2013. The genetic relatedness, serotype dominance and antibiotic resistance of isolates were investigated. A total of 46 strains were isolated from environmental samples (e.g., sediment, seawater and shrimp), whereas 249 strains were obtained from stools of patients with gastroenteritis. Nine different O serogroups and 16 serovars were identified. Serovars O3:K6 and O6:K46 were identified in both environmental and clinical strains. Whereas most environmental isolates carried the tdh gene (71.74%, 33/46), only three (6.52%) belonged to pandemic clones (O3:K6, O3:KUT and OUT:KUT). In contrast, 81.1% (202/249) of clinical isolates belonged to pandemic serotypes, with O3:K6 (tdh, toxRS/new, and/or orf8) representing the predominant serovar (97%, 196/202). This prevalence of pathogenic (tdh and/or trh positive) and O3:K6 pandemic V. parahaemolyticus isolates in this study were similar to those found from 2004 to 2010. As investigated by REP-PCR, genetic lineages of selected O3:K6 strains isolated in this study and some isolated earlier were nearly identical. Antimicrobial susceptibility testing showed that most strains (93.8%) were resistant to ampicillin but sensitive to chloramphenicol (98.8%). Multidrug resistance significantly increased from 8.6% (2004-2010) to 22.93% (2011-2013; p < 0.05). Our data indicate that pandemic O3:K6 clone has endemically established in the Pacific Coast of Mexico.

19.
Orthopedics ; 22(11): 1049-53, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10580823

RESUMO

This study evaluated the hydroxyapatite-coated femoral stem of the Bihapro hip prosthesis (Biomet Ltd, Bridgend, United Kingdom) using radiography, TC-99 scintigraphy, and bone densitometry. Thirty stems with >2 years of follow-up (mean: 31 months) were evaluated. No loosening or changes in the position of the implant were seen, and the mean subsidence was 2.2 mm. Radiography revealed a densification in the metaphyseal zone with reconstruction of the trabecular lines in 21 cases, while in 22 patients, radiolucent lines in the distal area of the femoral component were observed. Scintigraphy showed a diaphyseal normo-captation in 19 cases and a hypercaptation <1.4 with a mean index of 1.1 in 10 patients. Metaphyseal hypercaptation >1.4 was seen in 24 patients. Bone densitometry revealed increased density in the metaphyseal zones in 29 patients with a periprosthetic/normal bone quotient of 1.4.


Assuntos
Densidade Óssea , Prótese de Quadril , Densitometria , Estudos de Avaliação como Assunto , Comportamentos Relacionados com a Saúde , Articulação do Quadril/diagnóstico por imagem , Humanos , Estudos Prospectivos , Desenho de Prótese , Radiografia , Cintilografia , Tecnécio
20.
An Med Interna ; 20(6): 287-91, 2003 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-12848598

RESUMO

OBJECTIVE: To value the grade of anxiety and psychosomatic semiology in hypertensive patients treated with lercanidipine and to analyse their evolution. A secondary objective is to carry out a pharmacovigilance study with lercanidipine. MATERIAL AND METHODS: Prospective multicentre observational 6 month study in primary hypertensive patients with SBP between 140-180 mm Hg and/or 90-110 mm Hg DBP. After a washout period of 10 days, treatment with 10 mg (1-0-0) lercanidipine is initiated. If BP is not controlled treatment with ramipril 2.5 mg/day is instaured. Clinical check-ups are carried periodically with measurements of BP, Heart Rate, objective valuation of tolerance to the drug and observance. At the initiation and end of the study biochemical check-ups are carried out, the level of anxiety is measured using the STAI questionnaire (Trait subscale) (Evaluation in decatipes 0-4 without ansiety 4-7 moderate ansiety, 7-10 high ansiety) and the psychosomatic profile with a questionnaire designed by this group. (Scale 0-18; 0 large semiology, 18 without semiology). Clinical tolerance to the drug is valued both subjectively and objectively. RESULTS: On included 538 patients. On registred 54 drop out, with side effects (3.75/). Completed the study 484 (237 M, 247 F), 429 of them with Lercanidipine in monotherapy (88.6/). Mean age 60.9 +/- 10.7. Mean BMI 29.1 +/- 5. The grade of anxiety did not alter during the study passing from 4.6 +/- 1.7 at the beginning of the study to 4.5 +/- 1.7 at the end of the study (valuation in decatypes) (ns). The psychosomatic semiology changed favourably from 10.7 +/-4.2 to 12.5 +/- 3.7 (p<0.00005). The evolution according to sex is similar. The mean SBP decreased from 165.6 +/- 12.2 mm Hg to 137.9 +/- 10.4 mm Hg (p<0.00005) and the mean DBP decreased from 96.5 +/- 8.1 mm Hg to 81.0 +/- 6.1 mm Hg (p<0.00005). Clinical tolerance was very good. Biochemical parameters were modified substantially: initial cholesterolemia 227.7 mg/dl and final cholesterolemia 213.6 mg/dl (p<0.00005); initial glucose 108.4 mg/dl and final glucose 105.7 mg/dl (p<0.00005). CONCLUSIONS: The mean level of anxiety in the group studied is confirmed not to vary during the length of the study. Psychosomatic semiology is reduced being statistically significant. Lercanidipine is shown to be very effective as antihypertensive and well tolerated. 164


Assuntos
Anti-Hipertensivos/uso terapêutico , Ansiedade/etiologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/efeitos dos fármacos , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Transtornos Psicofisiológicos/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Ansiedade/tratamento farmacológico , Glicemia/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Colesterol/sangue , Complicações do Diabetes , Diabetes Mellitus/sangue , Di-Hidropiridinas/farmacologia , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/complicações , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transtornos Psicofisiológicos/tratamento farmacológico , Resultado do Tratamento
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