Fluorescence Liquid Biopsy for Cancer Detection Is Improved by Using Cationic Dendronized Hyperbranched Polymer.

(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FSscore), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.

Three-dimensional evaluation of accommodating intraocular lens shift and alignment in vivo.

OBJECTIVE: To quantify 3-dimensionally the anterior segment geometry, biometry, and lens position and alignment in patients before and after implantation of the Crystalens-AO (Bausch & Lomb, Rochester, NY) accommodating intraocular lens (A-IOL). DESIGN: Prospective, observational study. PARTICIPANTS: Ten patients (20 eyes) with cataract before and after implantation of the Crystalens-AO A-IOL. METHODS: Custom full anterior segment 3-dimensional (3-D) spectral optical coherence tomography (OCT) provided with quantification tools was used to image the cornea, iris, and natural lens preoperatively and intraocular lens postoperatively. Measurements were obtained under phenylephrine preoperatively and under natural viewing conditions and phenylephrine (for accommodative efforts ranging from 0 to 2.5 diopters [D]) and pilocarpine postoperatively. MAIN OUTCOME MEASURES: Three-dimensional quantitative anterior segment images, corneal geometry and power, anterior chamber depth (ACD), lens thickness, pupil diameter, A-IOL shift with accommodative effort or drug-induced accommodation, and A-IOL alignment. RESULTS: Crystalline lens and IOLs were visualized and quantified 3-dimensionally. The average ACD were 2.64±0.24 and 3.65±0.35 mm preoperatively and postoperatively (relaxed state), respectively, and they were statistically significantly correlated (although their difference was not statistically correlated with lens thickness). The A-IOL did not shift systematically with accommodative effort, with 9 lenses moving forward and 11 lenses moving backward (under natural conditions). The average A-IOL shift under stimulated accommodation with pilocarpine was -0.02±0.20 mm. The greatest forward shift occurred bilaterally in 1 patient (-0.49 mm in the right eye and -0.52 mm in the left eye, under pilocarpine). The high right/left symmetry in the horizontal tilt of the crystalline lens is disrupted on IOL implantation. Accommodative IOLs tend to be slightly more vertically tilted than the crystalline lens, with increasing tendency with accommodative effort. Two subjects showed postoperative IOL tilts >9 degrees. Changes in pupillary diameter correlated with pilocarpine-induced A-IOL axial shift. Intermediate accommodative demands (1.25 D) elicited the greater shifts in axial A-IOL location and tilt and pupil diameter. CONCLUSIONS: Quantitative 3-D anterior segment OCT allows full evaluation of the geometry of eyes implanted with A-IOLs preoperatively and postoperatively. High-resolution OCT measurements of the Crystalens 3-D positioning revealed small (and in many patients backward) A-IOL axial shifts with both natural or drug-induced accommodation, as well as tilt changes with respect to natural lens and accommodative effort.

Bowel Preparation for Colonoscopy Changes Serum Composition as Detected by Thermal Liquid Biopsy and Fluorescence Spectroscopy.

(1) Background: About 50% of prescribed colonoscopies report no pathological findings. A secondary screening test after fecal immunochemical test positivity (FIT+) would be required. Considering thermal liquid biopsy (TLB) as a potential secondary test, the aim of this work was to study possible interferences of colonoscopy bowel preparation on TLB outcome on a retrospective study; (2) Methods: Three groups were studied: 1/514 FIT(+) patients enrolled in a colorectal screening program (CN and CP with normal and pathological colonoscopy, respectively), with blood samples obtained just before colonoscopy and after bowel preparation; 2/55 patients from the CN group with blood sample redrawn after only standard 8-10 h fasting and no bowel preparation (CNR); and 3/55 blood donors from the biobank considered as a healthy control group; (3) Results: The results showed that from the 514 patients undergoing colonoscopy, 247 had CN and 267 had CP. TLB parameters in these two groups were similar but different from those of the blood donors. The resampled patients (with normal colonoscopy and no bowel preparation) had similar TLB parameters to those of the blood donors. TLB parameters together with fluorescence spectra and other serum indicators (albumin and C-reactive protein) confirmed the statistically significant differences between normal colonoscopy patients with and without bowel preparation; (4) Conclusions: Bowel preparation seemed to alter serum protein levels and altered TLB parameters (different from a healthy subject). The diagnostic capability of other liquid-biopsy-based methods might also be compromised. Blood extraction after bowel preparation for colonoscopy should be avoided.

Thermal Liquid Biopsy (TLB) of Blood Plasma as a Potential Tool to Help in the Early Diagnosis of Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is frequently characterized by a variety of clinical signs, often exhibiting little specificity. The diagnosis requires a combination of medical observations and instrumental tests, and any support for its objective assessment is helpful. OBJECTIVE: Herein, we describe the application of thermal liquid biopsy (TLB) of blood plasma samples, a methodology for predicting the occurrence of MS with a noninvasive, quick blood test. METHODS: TLB allows one to define an index (TLB score), which provides information about overall real-time alterations in plasma proteome that may be indicative of MS. RESULTS: This pilot study, based on 85 subjects (45 MS patients and 40 controls), showed good performance indexes (sensitivity and specificity both around 70%). The diagnostic methods better discriminate between early stage and low-burden MS patients, and it is not influenced by gender, age, or assumption of therapeutic drugs. TLB is more accurate for patients having low disability level (≤ 3.0, measured by the expanded disability status scale, EDSS) and a relapsing-remitting diagnosis. CONCLUSION: Our results suggest that TLB can be applied to MS, especially in an initial phase of the disease when diagnosis is difficult and yet more important (in such cases, accuracy of prediction is close to 80%), as well as in personalized patient periodic monitoring. The next step will be determining its utility in differentiating between MS and other disorders, in particular in inflammatory diseases.

Thermal Liquid Biopsy (TLB) Focused on Benign and Premalignant Pancreatic Cyst Diagnosis.

BACKGROUND: Current efforts in the identification of new biomarkers are directed towards an accurate differentiation between benign and premalignant cysts. Thermal Liquid Biopsy (TLB) has been previously applied to inflammatory and tumor diseases and could offer an interesting point of view in this type of pathology. METHODS: In this work, twenty patients (12 males and 8 females, average ages 62) diagnosed with a pancreatic cyst benign (10) and premalignant (10) cyst lesions were recruited, and biological samples were obtained during the endoscopic ultrasonography procedure. RESULTS: Proteomic content of cyst liquid samples was studied and several common proteins in the different groups were identified. TLB cyst liquid profiles reflected protein content. Also, TLB serum score was able to discriminate between healthy and cysts patients (71% sensitivity and 98% specificity) and between benign and premalignant cysts (75% sensitivity and 67% specificity). CONCLUSIONS: TLB analysis of plasmatic serum sample, a quick, simple and non-invasive technique that can be easily implemented, reports valuable information on the observed pancreatic lesion. These preliminary results set the basis for a larger study to refine TLB serum score and move closer to the clinical application of TLB providing useful information to the gastroenterologist during patient diagnosis.

A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides.

Alpha-fetoprotein (AFP) is a self protein expressed by fetal liver at high levels, but is transcriptionally repressed at birth. AFP is up-regulated in hepatocellular carcinomas, and patients with active disease could have plasma levels as high as 1 mg/mL. We previously identified four immunodominant HLA-A*0201-restricted peptides [hAFP(137-145) (PLFQVPEPV), hAFP(158-166) (FMNKFIYEI), hAFP(325-334) (GLSPNLNRFL), and hAFP(542-550) (GVALQTMKQ)] derived from human AFP that could stimulate specific T cell responses in healthy donor peripheral blood lymphocytes in vitro. We conducted a phase I/II clinical trial in which HLA-A*0201 patients with AFP-positive hepatocellular carcinoma were immunized with three biweekly intradermal vaccinations of the four AFP peptides pulsed onto autologous dendritic cells (DC). DCs were prepared from adherent peripheral blood mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. Sixteen subjects were enrolled and 10 were treated. Peripheral blood lymphocytes were isolated from these patients before, during, and after AFP peptide/DC immunization and were tested ex vivo with MHC tetramer and IFNgamma ELISPOT analysis. Six of 10 subjects expanded statistically significant levels of AFP-specific T cells postvaccine to at least one peptide by MHC tetramer. Also, 6 of 10 subjects increased IFNgamma producing AFP-specific T cell responses to at least one of the peptides postvaccination, by ELISPOT. We conclude that the human T cell repertoire is capable of responding to the AFP self antigen after the administration of AFP peptide-pulsed DC even in an environment of high circulating levels of this oncofetal antigen.

Quantitative EEG abnormalities in recently abstinent methamphetamine dependent individuals.

OBJECTIVE: Methamphetamine exposure is associated with long-lasting reductions in markers for dopaminergic neurons in preclinical models and probably in humans. Quantitative electroencephalography (EEG) has been used to characterize abnormalities in brain function in a number of disorders, including cocaine dependence, but this technique has not been used to characterize abnormalities associated with methamphetamine dependence. METHODS: The sample included 11 methamphetamine dependent subjects and 11 non-drug using volunteers. Methamphetamine dependent subjects were hospitalized for 4 days to document abstinence; non-drug using volunteers were studied as outpatients. EEGs were recorded in the eyes-closed resting state, and absolute EEG power in each frequency band (0.5-4, 4-8, 8-12, and 12-20 Hz) was quantitated using a fast Fourier transform. EEG power was log-transformed prior to analysis. Conventional, EEG tracings were interpreted by a qualified electroencephalographer who was blinded to the subjects' identity. RESULTS: Methamphetamine dependent volunteers with 4 days of abstinence had increased EEG power in the delta and theta bands. Power in the alpha and beta bands did not differ between the groups. Within the methamphetamine dependent group, a majority of the conventional EEGs were abnormal (64%), compared to 18% in the non-methamphetamine using group. CONCLUSIONS: Recently abstinent methamphetamine dependent subjects demonstrate QEEG abnormalities that are consistent with a generalized encephalopathy. SIGNIFICANCE: Encephalopathic changes in brain electrical activity, as found here in methamphetamine dependence, are frequently associated with a range of cognitive and psychiatric abnormalities, suggesting further avenues of investigation.

Calidad de la comunicación y actitud de los empleados ante procesos de cambio organizacional / Quality of the communcation and attitude of the employees in organizational change processes

El objetivo de la investigación fue determinar la relación entre la calidad de la comunicación y la actitud de los empleados ante procesos de cambio organizacional, en virtud de que algunas organizaciones tratan todos los cambios como algo que ocurre de manera accidental y que involucra las actividades de cambio que son proactivas y con propósito. El hombre es un ser productivo vinculado en el ambiente empresarial, que considera las actitudes como un proceso en el cual se obtiene más de lo esperado, ajustando el trabajo a los objetivos, propósitos y metas establecidas en la empresa. Bajo este contexto, el éxito o fracaso de una organización está causado por las cosas que los empleados hacen o dejan de hacer, de las actitudes que éstos asuman. El cambio planeado también se ocupa del comportamiento de los individuos y grupos dentro de la organización. La realización de este articulo reviste ser pertinente y actualizada, puesto que contribuye con el aporte de conocimientos en el área estratégica de cambio organizacional. El estudio se realizó bajo un diseño experimental aplicando la escala de resistencia al cambio de Oreg (2006) en una muestra recolectada en línea (n = 174) y compuesta por dos grupos aleatorios. Los resultados confirman que el grupo de participantes expuestos a una comunicación con argumentos de alta calidad mostró menos resistencia al cambio organizacional que el grupo de participantes expuestos a una comunicación con argumentos de baja calidad. Finalmente, se discute la importancia de los hallazgos para futuras investigaciones e implicaciones prácticas para la gestión de cambios organizacionales.

It has been confirmed that the organizations have faced various changes and challenges generated in the market, which have originated a new focus of study focused on people to execute the processes, emphasizing the creation of work methodologies that support the efforts of the employees to generate the changes, in such a way that the organizations can become global, flexible, productive, in addition to generate strategies oriented to the employee and the strategy to the client. In this sense, it is necessary to apply methods or techniques that allow optimizing the development of production processes, as well as the administration of organizations, by virtue of improving work activities and production processes. In this context, for the execution of organizational processes, a human talent is required that is committed and identified with the culture of the company, which is why the role played by the individual within any organization is highlighted. generate attitudes that promote communication, as a promoter of the functioning of the activities inherent to organizational change. The main of this research was to determine the relationship between the quality of the communication and the attitude of the employees towards processes of organizational chang. This objetive is proposed because some organizations treat all the changes as nonplanned change; that involves organizational change product of proactive and purposeful activities; inside in the business environment the human being define the attitudes as a process in which more is obtained than expected; adjusting the work, the objectives, purposes and goals established in the company. In this context, the organizational successor failure is caused by the employees do at the organization, the attitudes that they assume, the planned change that employees propose, also how they deal with the individuals and groups behavior. According to what has been said, make this research in relevant because it contributes to the scientific knowledge in the organizational change area. The study was carried out under an experimental design applying the resistance to change scale of Oreg (2006) in a sample collected online (n = 174) and composed of two random groups. To carry out this research, it was necessary to establish the sample criterion: we worked from an integrated sample with a total of 174 people, which were randomly selected, through social networks and the virtual campus of a distance university in Germany. The stratification of the sample was made up of women (53%) and men (47%), employees with ages mainly between 21 and 40 years of age (60%), between 40 and 60 years of age (36%) and others (4%). Regarding the level of education, we found that 70% of the participants had a bachelor's degree, 26% had a university degree and 4% others. The majority of the participants (68%) had a time of belonging to the company from 1 to 5 years and 32% had more than 10 years. In this research, a scale was used that differentiates three dimensions of resistance to change (affective, cognitive and behavioral). To investigate the possible links between the quality of the arguments (strong or weak) and the three dimensions of resistance to change, a Student's ttest was carried out for each of the dimensions. Because multiple comparisons were made, the likelihood of committing type I error increased. In order to adjust the statistical results, the Bonferroni correction was applied (Bühner & Ziegler, 2009). The results confirm that the group of participants exposed to a communication with high quality arguments showed less resistance to organizational change than the group of participants exposed to a communication with low quality arguments. Finally, the importance of the findings for future research and practical implications for the management of organizational changes are discussed.

Aberrometry in patients implanted with accommodative intraocular lenses.

PURPOSE: To evaluate the objective accommodative response, change of aberrations, and depth of focus in eyes implanted with the Crystalens accommodative intraocular lens (IOL) at different accommodative demands. DESIGN: Prospective, observational study. METHODS: Eleven cataract patients (22 eyes) who underwent implantation of a Crystalens accommodative IOL, and control groups of 9 normal subjects (17 eyes) and 17 pseudophakic patients (17 eyes) implanted with monofocal IOLs were evaluated. A custom-developed laser ray tracing aberrometer was used to measure the optical aberrations. The monochromatic wave aberrations were described using a sixth-order Zernike polynomial expansion. Measurements were obtained under dilated and natural viewing conditions (for accommodative efforts ranging from 0 to 2.5 diopters [D]). The accommodative response was obtained by analyzing changes in paraxial defocus (associated to changes in defocus) and by evaluating the differences in the effective defocus (associated with defocus, spherical aberrations, and pupil diameter) with the accommodative demand. Depth of focus was estimated from through-focus objective optical quality. RESULTS: Wave aberration measurements were highly reproducible. Vertical trefoil (Z3(-3)) was the predominant higher-order aberration in the Crystalens group and significantly higher (P < .0001) than in the young group, but similar to the monofocal IOL group. The coma root mean square also was higher (P < .005) in the Crystalens group than in the young group. On average, the defocus term (Z2(0)), astigmatism, or higher-order aberrations did not change systematically with accommodative demand in Crystalens eyes. As found for paraxial defocus, the effective defocus in Crystalens eyes did not show significant differences between conditions: 0.34 ± 0.48 D (far), 0.32 ± 0.50 D (intermediate), and 0.34 ± 0.44 D (near). Depth of focus was statistically significantly higher in the Crystalens eyes than in the control groups. CONCLUSIONS: The accommodative response of eyes implanted with the Crystalens accommodative IOLs, measured objectively using laser ray tracing aberrometry, was lower than 0.4 D in all eyes. Several subjects showed changes in astigmatism, spherical aberration, trefoil, and coma with accommodation, which must arise from geometrical and alignment changes in the lens with accommodative demand. Pseudoaccommodation from increased depth of focus may contribute to near vision functionality in Crystalens-implanted patients.

In vivo chromatic aberration in eyes implanted with intraocular lenses.

PURPOSE: To measure in vivo and objectively the monochromatic aberrations at different wavelengths, and the chromatic difference of focus between green and infrared wavelengths in eyes implanted with two models of intraocular lenses (IOL). METHODS: EIGHTEEN EYES PARTICIPATED IN THIS STUDY: nine implanted with Tecnis ZB99 1-Piece acrylic IOL and nine implanted with AcrySof SN60WF IOL. A custom-developed laser ray tracing (LRT) aberrometer was used to measure the optical aberrations, at 532 nm and 785 nm wavelengths. The monochromatic wave aberrations were described using a fifth-order Zernike polynomial expansion. The chromatic difference of focus was estimated as the difference between the equivalent spherical errors corresponding to each wavelength. RESULTS: Wave aberration measurements were highly reproducible. Except for the defocus term, no significant differences in high order aberrations (HOA) were found between wavelengths. The average chromatic difference of focus was 0.46 ± 0.15 diopters (D) in the Tecnis group, and 0.75 ± 0.12 D in the AcrySof group, and the difference was statistically significant (P < 0.05). Chromatic difference of focus in the AcrySof group was not statistically significantly different from the Longitudinal chromatic aberration (LCA) previously reported in a phakic population (0.78 ± 0.16 D). The impact of LCA on retinal image quality (measured in terms of Strehl ratio) was drastically reduced when considering HOA and astigmatism in comparison with a diffraction-limited eye, yielding the differences in retinal image quality between Tecnis and AcrySof IOLs not significant. CONCLUSIONS: LRT aberrometry at different wavelengths is a reproducible technique to evaluate the chromatic difference of focus objectively in eyes implanted with IOLs. Replacement of the crystalline lens by the IOL did not increase chromatic difference of focus above that of phakic eyes in any of the groups. The AcrySof group showed chromatic difference of focus values very similar to physiological values in young eyes.

Full OCT anterior segment biometry: an application in cataract surgery.

In vivo three-dimensional (3-D) anterior segment biometry before and after cataract surgery was analyzed by using custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT). The system was provided with custom algorithms for denoising, segmentation, full distortion correction (fan and optical) and merging of the anterior segment volumes (cornea, iris, and crystalline lens or IOL), to provide fully quantitative data of the anterior segment of the eye. The method was tested on an in vitro artificial eye with known surfaces geometry at different orientations and demonstrated on an aging cataract patient in vivo. Biometric parameters CCT, ACD/ILP, CLT/ILT Tilt and decentration are retrieved with a very high degree of accuracy. IOL was placed 400 µm behind the natural crystalline lens, The IOL was aligned with a similar orientation of the natural lens (2.47 deg superiorly), but slightly lower amounts (0.77 deg superiorly). The IOL was decentered superiorly (0.39 mm) and nasally (0.26 mm).

Exploring factors in the decision to choose sterilization vs alternatives in rural El Salvador.

CONTEXT: To explore the factors that influence rural Salvadoran women to undergo tubal sterilization versus opting for alternative methods of family planning. EVIDENCE ACQUISITION: A moderator fluent in English and Spanish conducted eleven 90-minute focus groups consisting of 5-10 women each. Eligible women in the municipality of San Pedro Perulapan, El Salvador, were identified and recruited by local health workers. Participant demographics and information about family planning decisions were collected through detailed notes and tape-recorded sessions. The tapes were transcribed verbatim, and all data were analyzed using grounded theory procedures to identify common themes. EVIDENCE SYNTHESIS: Eighty women aged 24-45 years who had previously been sterilized participated in the study. Three major themes influenced a woman's decision to undergo sterilization instead of opting for alternative forms of family planning: (1) availability: tubal sterilization is readily available, (2) fears about side effects of other methods: these women associated negative side effects with other forms of family planning, (3) effectiveness: the women in these focus groups thought sterilization was more effective than other forms of family planning. CONCLUSIONS: This study shows that there is a lack of information, and misinformation, about other effective methods of contraception, especially the intrauterine device and oral contraceptives. Reproductive health education projects, especially those providing services in locations similar to rural El Salvador, should focus on providing accurate information about all forms of contraception, including tubal sterilization.

Methamphetamine abstinence syndrome: preliminary findings.

Retrospective reports suggest that chronic use of methamphetamine is associated with a prolonged abstinence syndrome; however, there are no prospective studies confirming this. Nineteen non-treatment-seeking methamphetamine-dependent volunteers participated in a study of mood during initial abstinence. Moderate levels of depression were reported during the first several days of abstinence, with minimal levels reported thereafter. The most prominent symptoms were anhedonia, irritability, and poor concentration. The abstinence syndrome associated with methamphetamine dependence varied considerably in intensity and duration but generally was mild and resolved quickly for most individuals.