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1.
Nat Commun ; 12(1): 1638, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712576

RESUMO

Key insights in materials at extreme temperatures and pressures can be gained by accurate measurements that determine the electrical conductivity. Free-electron laser pulses can ionize and excite matter out of equilibrium on femtosecond time scales, modifying the electronic and ionic structures and enhancing electronic scattering properties. The transient evolution of the conductivity manifests the energy coupling from high temperature electrons to low temperature ions. Here we combine accelerator-based, high-brightness multi-cycle terahertz radiation with a single-shot electro-optic sampling technique to probe the evolution of DC electrical conductivity using terahertz transmission measurements on sub-picosecond time scales with a multi-undulator free electron laser. Our results allow the direct determination of the electron-electron and electron-ion scattering frequencies that are the major contributors of the electrical resistivity.

2.
J Synchrotron Radiat ; 27(Pt 3): 796-798, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381783

RESUMO

The electron linear accelerators driving modern X-ray free-electron lasers can emit intense, tunable, quasi-monochromatic terahertz (THz) transients with peak electric fields of V Å-1 and peak magnetic fields in excess of 10 T when a purpose-built, compact, superconducting THz undulator is implemented. New research avenues such as X-ray movies of THz-driven mode-selective chemistry come into reach by making dual use of the ultra-short GeV electron bunches, possible by a rather minor extension of the infrastructure.

3.
J Synchrotron Radiat ; 27(Pt 1): 11-16, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31868730

RESUMO

A simple and robust tool for spatio-temporal overlap of THz and XUV pulses in in-vacuum pump-probe experiments is presented. The technique exploits ultrafast changes of the optical properties in semiconductors (i.e. silicon) driven by ultrashort XUV pulses that are probed by THz pulses. This work demonstrates that this tool can be used for a large range of XUV fluences that are significantly lower than when probing by visible and near-infrared pulses. This tool is mainly targeted at emerging X-ray free-electron laser facilities, but can be utilized also at table-top high-harmonics sources.

4.
Struct Dyn ; 6(3): 034301, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31123698

RESUMO

The ultrafast electronic decay of HCl molecules in the time domain after resonant core excitation was measured. Here, a Cl-2p core electron was promoted to the antibonding σ* orbital initiating molecular dissociation, and simultaneously, the electronic excitation relaxes via an Auger decay. For HCl, both processes compete on similar ultrashort femtosecond time scales. In order to measure the lifetime of the core hole excitation, we collinearly superimposed 40 fs soft x-ray pulses with intense terahertz (THz) radiation from the free-electron laser in Hamburg (FLASH). Electrons emitted from the molecules are accelerated (streaked) by the THz electric field where the resulting momentum change depends on the field's phase at the instant of ionization. Evaluation of a time-shift between the delay-dependent streaking spectra of photo- and Auger electrons yields a decay constant of (11 ± 2) fs for LMM Auger electrons. For further validation, the method was also applied to the MNN Auger decay of krypton. Reproduction of the value already published in the literature confirms that a temporal resolution much below the duration of the exciting x-ray pulses can be reached.

5.
J Mycol Med ; 28(4): 623-627, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30166063

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of an alternative treatment in a form of recommended diet modification during and after conventional treatment with antifungals in patients with a chronic form of intestinal Candida overgrowth (ICOG). METHODS: The study included patients with ICOG divided in two subgroups: patients treated with nystatin and recommended diet regime (study group-SG) and the patients treated only with nystatin (control group-CG). After treatment, the mycological control examination and follow-up were performed two times: the first one within ten days after the completion of antifungal treatment, and the second one three months after the treatment initialization. RESULTS: A total of 120 patients finished the study: 80 from the SG and 40 from the CG. At the first mycological control examination of SG patients stools, we noted satisfactory antifungal and symptomatic effect in 56 out of 80 (70.0%) patients and 29 out of 40 (72.5%) in CG, with no statistically significant difference. However, at the second control stool examination, significantly higher percent (85%) of cured patients was recorded after three months of the recommended diet comparing with CG-17 out of 40 (42.5%). CONCLUSION: Results of this pilot study showed that patients who adhered to diet modification during and after treatment with nystatin had better outcomes of ICOG and strongly suggest the need for diet modification in these patients which recommendation could reduce excessive prescription of antifungals.


Assuntos
Candida/crescimento & desenvolvimento , Candidíase/dietoterapia , Enteropatias/dietoterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Candida/classificação , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/patologia , Fezes/microbiologia , Feminino , Seguimentos , Humanos , Enteropatias/tratamento farmacológico , Enteropatias/microbiologia , Enteropatias/patologia , Masculino , Pessoa de Meia-Idade , Nistatina/uso terapêutico , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
6.
Hum Reprod ; 33(6): 1141-1148, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688494

RESUMO

STUDY QUESTION: Do patient-specific features contribute to the differences between measured serum anti-Müllerian hormone (AMH) concentrations and AMH values expected from the corresponding antral follicle count (AFC)? SUMMARY ANSWER: Patient-specific features contribute to the differences between measured AMH values and AMH values expected from the corresponding AFC (AMHp), potentially through their effect on follicular AMH production. WHAT IS KNOWN ALREADY: Both patient counselling and patient management could be hampered by finding of disagreement between AFC and AMH if both are used for the prediction of ovarian response. The difference between measured AMH concentrations and AMH values expected according to the corresponding AFC cannot be entirely explained by the technical limitations of counting of antral follicles and analytical variability of the AMH assay used. STUDY DESIGN, SIZE, DURATION: This retrospective study analysed medical records of 1097 IVF patients collected between March 2011 and July 2013. PARTICIPANT/MATERIALS, SETTING, METHODS: The study population (N = 1097) included 705 (64.3%) women with normal ovarian morphology and 392 (35.7%) women with polycystic ovarian morphology, aged 20-44 years, who underwent their first IVF cycle in a single clinical centre. AMH was measured by a routine laboratory method and predicted AMH (AMHp) values were calculated using the linear regression equation (AMHp = -4.4 + 1.5 × AFC). The absolute value of the difference between AMH and AMHp was considered to be the measure of the degree of AMH-AFC agreement. The association of the difference between AMH and AMHp with clinical and biochemical parameters was investigated in both the higher-than-predicted (HTP) group comprising patients with AMH higher than AMHp (N = 466) and the lower-than-predicted (LTP) group comprising patients with AMH lower than AMHp (N = 631). MAIN RESULTS AND THE ROLE OF CHANCE: Patients in the HTP group had significantly longer menstrual cycle length and higher AMH and LH concentrations but lower AFC and FSH concentration than their counterparts in the LTP group. There was a significant association of absolute value of the difference between AMH and AMHp with age, menstrual cycle length, AFC, FSH and testosterone in both groups (P < 0.001). The difference between AMH and AMHp was exclusively correlated to LH in the HTP group (r = 0.159, P < 0.001) and to BMI in the LTP group (r = 0.231, P < 0.001), respectively. Multiple regression analysis revealed that only LH was significantly related to the difference between AMH and AMHp in the HTP group, independently from AFC. In the LTP group, BMI, menstrual cycle length, FSH and testosterone were found associated with the difference between AMH and AMHp, independently from AFC. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study is selection bias. Data analysed in this study were collected from medical records of patients undergoing IVF treatment in a single department of human reproduction which precludes generalization of the results to women of different geographic origin, ethnicity, race and reproductive status. WIDER IMPLICATION OF THE FINDINGS: AMH higher than expected for a given AFC could suggest up-regulated AMH secretion (a typical feature of polycystic ovary syndrome) while AMH lower than expected from the corresponding AFC suggest down-regulated AMH secretion that could be seen as an early symptom of diminished ovarian reserve and premature ovarian insufficiency. In other words, when challenged against AFC, the serum AMH level is not only a quantitative but also a qualitative follicle marker, in relation with clinical and endocrine parameters. STUDY FUNDING/COMPETING INTEREST(S): No study funding was obtained for this study. The authors have no conflict of interest(s) to declare. TRIAL REGISTRATION NUMBER: Non-applicable.


Assuntos
Hormônio Antimülleriano/sangue , Reserva Ovariana , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Modelos Lineares , Hormônio Luteinizante/sangue , Variações Dependentes do Observador , Folículo Ovariano/diagnóstico por imagem , Folículo Ovariano/patologia , Síndrome do Ovário Policístico/sangue , Valor Preditivo dos Testes , Estudos Retrospectivos , Ultrassonografia
7.
J Mycol Med ; 28(2): 236-248, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29605542

RESUMO

Traditional, culture based methods for the diagnosis of fungal infections are still considered as gold standard, but they are time consuming and low sensitive. Therefore, in order to overcome the limitations, many researchers have focused on the development of new immunological and molecular based rapid assays that could enable early diagnosis of infection and accurate identification of fungal pathogens causing superficial and invasive infection. In this brief review, we highlighted the advantages and disadvantages of conventional diagnostic methods and possibility of non-culture based assays in diagnosis of superficial fungal infections and presented the overview on currently available immunochromatographic assays as well as availability of biomarkers detection by immunodiagnostic procedures in prompt and accurate diagnosis of invasive fungal infections. In addition, we presented diagnostic efficiency of currently available molecular panels and researches in this area.


Assuntos
Fungos/isolamento & purificação , Imunoensaio , Técnicas de Diagnóstico Molecular/métodos , Micoses/diagnóstico , Bioensaio , Dermatomicoses/diagnóstico , Fungos/patogenicidade , Humanos , Testes Imunológicos , Infecções Fúngicas Invasivas/diagnóstico , Reação em Cadeia da Polimerase
8.
Braz J Med Biol Res ; 50(8): e6185, 2017 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-28746468

RESUMO

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.


Assuntos
Adenosina/uso terapêutico , Alprostadil/uso terapêutico , Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Chinchila , Modelos Animais de Doenças , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino
9.
Struct Dyn ; 4(2): 024301, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28382317

RESUMO

Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession.

10.
Oncogene ; 36(13): 1804-1815, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-27721407

RESUMO

Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes p53 , Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Animais , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Humanos , Camundongos , Camundongos Knockout , Mutação , Neoplasias Pancreáticas/patologia , Regiões Promotoras Genéticas , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/genética
11.
Braz. j. med. biol. res ; 50(8): e6185, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-888975

RESUMO

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.


Assuntos
Animais , Masculino , Feminino , Adenosina/uso terapêutico , Alprostadil/uso terapêutico , Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Chinchila , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/patologia
12.
Cell Mol Biol (Noisy-le-grand) ; 62(9): 27-33, 2016 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-27585258

RESUMO

Biofilms are complex communities of microorganisms, responsible for more than 60% of the chronic human infections and they represent one of the leading concerns in medicine. Pseudomonas aeruginosa is human pathogenic bacteria which causes numerous diseases and is known for its ability to produce biofilm. Ocimum basilicum L. (basil) and Salvia officinalis L. (sage) are widely used plants in traditional medicine for the treatment of different conditions. Therefore, the aim of this study was to investigate the potential of basil and sage essential oils against P. aeruginosa biofilm producing strains. The efficacy of two essential oils on P. aeruginosa biofilm forming ability was determined using crystal violet method. Out of 15 strains isolated from different clinical biological samples, two were strong, 11 moderate and one weak biofilm producer. Good efficacy of sage essential oil towards strong and weak biofilm producers, but not of basil essential oil, was observed. In the case of moderate biofilm producers, 81.8% showed lower biofilm production after incubation with the sage oil, while 63.6% showed the reduction of biofilm production after basil essential oil treatment. The obtained results showed high potential of both oils for the treatment of persistent infections caused by Pseudomonas aeruginosa biofilms.


Assuntos
Biofilmes/efeitos dos fármacos , Ocimum basilicum/química , Óleos Voláteis/farmacologia , Pseudomonas aeruginosa/fisiologia , Salvia officinalis/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Orelha/microbiologia , Olho/microbiologia , Humanos , Ocimum basilicum/metabolismo , Óleos Voláteis/química , Faringe/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Salvia officinalis/metabolismo , Pele/microbiologia
13.
Sci Rep ; 6: 22256, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26924651

RESUMO

Ultrashort flashes of THz light with low photon energies of a few meV, but strong electric or magnetic field transients have recently been employed to prepare various fascinating nonequilibrium states in matter. Here we present a new class of sources based on superradiant enhancement of radiation from relativistic electron bunches in a compact electron accelerator that we believe will revolutionize experiments in this field. Our prototype source generates high-field THz pulses at unprecedented quasi-continuous-wave repetition rates up to the MHz regime. We demonstrate parameters that exceed state-of-the-art laser-based sources by more than 2 orders of magnitude. The peak fields and the repetition rates are highly scalable and once fully operational this type of sources will routinely provide 1 MV/cm electric fields and 0.3 T magnetic fields at repetition rates of few 100 kHz. We benchmark the unique properties by performing a resonant coherent THz control experiment with few 10 fs resolution.

14.
Case Rep Ophthalmol Med ; 2015: 230801, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26171265

RESUMO

Purpose. To present a case of cataract surgery performed in a patient with a refractive corneal inlay in place. Methods. A 48-year-old female patient presented to our institute with bilateral cataract. The patient had undergone refractive corneal inlay implantation three years ago in her right, nondominant eye for presbyopia correction. Biometry and intraocular lens (IOL) power calculation were performed without removing the inlay. Phacoemulsification and IOL insertion were carried out in both eyes in a usual manner. Results. On day one postoperatively, the patient achieved binocular uncorrected distance visual acuity 20/20 and uncorrected near visual acuity J1. The vision remained stable during the one-year follow-up period. Conclusion. Cataract surgery was performed in a standard manner in a patient with Presbia Microlens corneal inlay in place. Visual outcomes for both near and distance vision were satisfactory.

15.
Hum Reprod ; 30(8): 1927-33, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26048913

RESUMO

STUDY QUESTION: Is intrinsic dysregulation of granulosa cells (GC) and consequent increases in the per-follicle production of anti-Müllerian hormone (AMH), correlated with the phenotypic presentation of women with polycystic ovaries? SUMMARY ANSWER: Involvement of intrinsic GC dysregulation in oligo-anovulation associated with polycystic ovary syndrome (PCOS) is likely because among women with PCOS, those with oligo-amenorrhea have higher per-follicle AMH production than those who ovulate normally, irrespective of their androgen and/or metabolic status. WHAT IS KNOWN ALREADY: Women with PCOS have higher serum AMH level than non-PCOS women due to an increased follicle number and excessive AMH production per follicle, the latter reflecting a putative GC dysfunction that may vary between PCOS phenotypes. STUDY DESIGN, SIZE, DURATION: This is a retrospective analysis of data collected from 1021 women undergoing infertility evaluation from March 2011 to October 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with polycystic ovarian morphology (PCOM) who met the Rotterdam criteria for PCOS (n = 272), women with PCOM only (n = 168) and controls (n = 581). MAIN RESULTS AND THE ROLE OF CHANCE: We used serum AMH to antral follicle count (AFC) ratio (AMH/AFC) as a marker of per-follicle AMH production and checked whether this ratio was associated with the PCOS phenotype and to the menstrual, androgen and metabolic status in women with PCOS, women with PCOM only and in controls. AMH/AFC was significantly higher in oligo-amenorrheic women with PCOS than in eumenorrheic women with PCOS or PCOM (P < 0.001) but also in the latter group compared with controls (P < 0.001) regardless of androgen status. Stepwise discriminant analysis yielded a significant score for the menstrual status with a discriminant power of 26.5% (P < 0.001). This score included AFC, AMH/AFC, waist circumference and LH with partial R(2) of 0.172, 0.042, 0.024 and 0.023, respectively. LIMITATIONS, REASONS FOR CAUTION: The AMH to AFC ratio as a surrogate marker for average AMH may be subject to error because follicles below the sensitivity limit of the ultrasonography used may also contribute to serum AMH concentration and secondly, AFC can be subjective. WIDER IMPLICATIONS OF THE FINDINGS: The higher AMH/AFC in women with PCOM only than in controls suggests that isolated PCOM may represent a PCOS-like phenotype in which an inherent dysfunction of GC exists but is too mild to affect the ovulatory process. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER: Non-applicable.


Assuntos
Hormônio Antimülleriano/sangue , Células da Granulosa/metabolismo , Folículo Ovariano/metabolismo , Síndrome do Ovário Policístico/metabolismo , Adulto , Feminino , Humanos , Ciclo Menstrual/metabolismo , Estudos Retrospectivos , Adulto Jovem
16.
Hum Reprod ; 29(11): 2536-43, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25267785

RESUMO

STUDY QUESTION: Can cluster analysis can be used to identify a homogeneous subpopulation of women with polycystic ovarian morphology (PCOM) within a very large population of control women in a non-subjective way? SUMMARY ANSWER: Identification and exclusion of the cluster corresponding to women with PCOM from controls improved the diagnostic power of serum anti-Müllerian hormone (AMH) level and follicle number per ovary (FNPO) in discriminating between women with or without polycystic ovary syndrome (PCOS). WHAT IS KNOWN ALREADY: There is disagreement as to whether women with PCOM should be excluded from the control population when establishing FNPO and AMH diagnostic thresholds for the definition of PCOS and how to identify such women. It has been demonstrated that cluster analysis can detect women with PCOM within the control population through a set of classifying variables among which the most relevant was AMH. The adequacy of this approach has not been confirmed in other clinical settings. STUDY DESIGN, SIZE, DURATION: This was a retrospective study using clinical and laboratory data derived from the computerized database. The data were collected from March 2011 to May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included 893 patients referred for routine infertility evaluation and treatment. The patients were divided into three groups: (i) the control group (n = 621) included women with regular menstrual cycles and no signs of hyperandrogenism (HA), (ii) the full-blown PCOS group (n = 95) consisted of women who were diagnosed as having PCOS based on the presence of both HA and oligo/amenorrhoea (OA), (iii) the mild PCOS group included women with only two items of the Rotterdam classification, i.e. PCOM at ultrasonography according to the FNPO threshold of 12 or more and either OA (n = 110) or HA (n = 67). MAIN RESULTS AND THE ROLE OF CHANCE: After exclusion of women with PCOM from the controls, the AMH threshold of 28 pmol/l with specificity 97.5% and sensitivity 84.2% [area under the curve (AUC) 0.948 (95% confidence interval (CI) 0.915-0.982)] and FNPO threshold of 12 with specificity 92.5% and sensitivity 83.2% [AUC 0.940 (95% CI 0.909-0.971)] for identifying PCOS were derived from the receiver operating characteristic curve analysis. The AMH threshold of 28 pmol/l had the same specificity for discriminating the mild and the full-blown PCOS phenotypes from controls. LIMITATIONS, REASONS FOR CAUTION: There was no selection bias other than being evaluated for infertility treatment, however, this could also be considered as a limitation of the study as these women may not necessarily be a representative sample of the general population. The study demonstrated that serum AMH has intrinsically a very high potency to detect women with PCOM within a control group. However, the AMH threshold is specific for this method and clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: AMH threshold value for the definition of PCOM is method specific and cannot be universally applied. This study confirmed the results of previous studies that cluster analysis can identify women with PCOM within the very large control population without using a predefined diagnostic threshold for FNPO, and that AMH can detect women with PCOM with a high specificity. The exclusion of PCOM women from the controls by using a cluster analysis should be considered when establishing reference intervals and decision threshold values for various parameters used to characterize PCOS. STUDY FUNDING/COMPETING INTERESTS: The authors have no funding/competing interest(s) to declare.


Assuntos
Hormônio Antimülleriano/sangue , Ciclo Menstrual/sangue , Ovário/patologia , Síndrome do Ovário Policístico/diagnóstico , Adulto , Glicemia , Análise por Conglomerados , Bases de Dados Factuais , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Nat Commun ; 4: 1731, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23591898

RESUMO

The resolution of ultrafast studies performed at extreme ultraviolet and X-ray free-electron lasers is still limited by shot-to-shot variations of the temporal pulse characteristics. Here we show a versatile single-shot temporal diagnostic tool that allows the determination of the extreme ultraviolet pulse duration and the relative arrival time with respect to an external pump-probe laser pulse. This method is based on time-resolved optical probing of the transient reflectivity change due to linear absorption of the extreme ultraviolet pulse within a solid material. In this work, we present measurements performed at the FLASH free-electron laser. We determine the pulse duration at two distinct wavelengths, yielding (184±14) fs at 41.5 nm and (21±19) fs at 5.5 nm. Furthermore, we demonstrate the feasibility to operate the tool as an online diagnostic by using a 20-nm-thin Si3N4 membrane as target. Our results are supported by detailed numerical and analytical investigations.

18.
Curr Med Chem ; 20(7): 932-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23210781

RESUMO

Microbial infectious diseases continue to be one of the leading causes of morbidity and mortality. It has been estimated that microbial species comprise about 60% of the Earth's biomass. This, together with the fact that their genetic, metabolic and physiological diversity is extraordinary, makes them a major threat to the health and development of populations across the world. Widespread antibiotic resistance, the emergence of new pathogens in addition to the resurgence of old ones, and the lack of effective new therapeutics exacerbate the problems. Thus, the need to discover and develop new antimicrobial agents is critical to improve mankind's future health. Plant secondary metabolites (PSMs) offer particular promise in this sense. Plant Kingdom could be considered a rich source of the most diverse structures (e.g. there are more than 12,000 known alkaloids, more than 8,000 phenolic compounds and over 25,000 different terpenoids), many of which were proven to possess strong antimicrobial properties (e.g. thymol, eurabienol, etc.). In many instances, PSMs can be easily isolated from the plant matrix, either in pure state or in the form of mixtures of chemically related compounds. What is also important is that the development of bacterial resistance toward natural plant products (that are generally regarded as eco-friendly) has been thus far documented in a very limited number of cases (e.g. for reserpine). Having all of the mentioned advantages of PSMs as potential antimicrobials in mind, a major question arises: why is it that there are still no commercially available or commonly used antibiotics of plant origin? This review tries to give a critical answer to this question by considering potential mechanisms of antimicrobial action of PSMs (inhibition of cell wall or protein synthesis, inducing leakage from the cells by tampering with the function of the membranes, interfering with intermediary metabolisms or DNA/RNA synthesis/function), as well as their physical and chemical properties (e.g. hydrophilicity/lipophilicity, chemical stability). To address the possible synergistic/antagonistic effects between PSMs and with standard antibiotics, special attention has been given to the antimicrobial activity of PSM-mixtures (e.g. essential oils, plant extracts). Moreover, possible ways of overcoming some of PSMs molecular limitations in respect to their usage as potential antibiotics were also discussed (e.g. derivatization that would enable fine tuning of certain molecular characteristics).


Assuntos
Anti-Infecciosos/química , Plantas/metabolismo , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas/química , Plasmodium/efeitos dos fármacos
20.
Phys Rev Lett ; 106(21): 217401, 2011 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-21699341

RESUMO

We used ultrafast resonant soft x-ray diffraction to probe the picosecond dynamics of spin and orbital order in La(0.5)Sr(1.5)MnO(4) after photoexcitation with a femtosecond pulse of 1.5 eV radiation. Complete melting of antiferromagnetic spin order is evidenced by the disappearance of a (1/4,1/4,1/2) diffraction peak. On the other hand, the (1/4,1/4,0) diffraction peak, reflecting orbital order, is only partially reduced. We interpret the results as evidence of destabilization in the short-range exchange pattern with no significant relaxation of the long-range Jahn-Teller distortions. Cluster calculations are used to analyze different possible magnetically ordered states in the long-lived metastable phase. Nonthermal coupling between light and magnetism emerges as a primary aspect of photoinduced phase transitions in manganites.

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