Population dynamics of potentially harmful haplotypes: a pedigree analysis.

BACKGROUND: The identification of low-frequency haplotypes, never observed in homozygous state in a population, is considered informative on the presence of potentially harmful alleles (candidate alleles), putatively involved in inbreeding depression. Although identification of candidate alleles is challenging, studies analyzing the dynamics of potentially harmful alleles are lacking. A pedigree of the highly endangered Gochu Asturcelta pig breed, including 471 individuals belonging to 51 different families with at least 5 offspring each, was genotyped using the Axiom PigHDv1 Array (658,692 SNPs). Analyses were carried out on four different cohorts defined according to pedigree depth and at the whole population (WP) level. RESULTS: The 4,470 Linkage Blocks (LB) identified in the Base Population (10 individuals), gathered a total of 16,981 alleles in the WP. Up to 5,466 (32%) haplotypes were statistically considered candidate alleles, 3,995 of them (73%) having one copy only. The number of alleles and candidate alleles varied across cohorts according to sample size. Up to 4,610 of the alleles identified in the WP (27% of the total) were present in one cohort only. Parentage analysis identified a total of 67,742 parent-offspring incompatibilities. The number of mismatches varied according to family size. Parent-offspring inconsistencies were identified in 98.2% of the candidate alleles and 100% of the LB in which they were located. Segregation analyses informed that most potential candidate alleles appeared de novo in the pedigree. Only 17 candidate alleles were identified in the boar, sow, and paternal and maternal grandparents and were considered segregants. CONCLUSIONS: Our results suggest that neither mutation nor recombination are the major forces causing the apparition of candidate alleles. Their occurrence is more likely caused by Allele-Drop-In events due to SNP calling errors. New alleles appear when wrongly called SNPs are used to construct haplotypes. The presence of candidate alleles in either parents or grandparents of the carrier individuals does not ensure that they are true alleles. Minimum Allele Frequency thresholds may remove informative alleles. Only fully segregant candidate alleles should be considered potentially harmful alleles. A set of 16 candidate genes, potentially involved in inbreeding depression, is described.

Bond Selective Photochemistry at Metal Nanoparticle Surfaces: CO Desorption from Pt and Pd.

The use of visible photon fluxes to influence catalytic reactions on metal nanoparticle surfaces has attracted attention based on observations of reaction mechanisms and selectivity not observed under equilibrium heating. These observations suggest that photon fluxes can selectively impact the rates of certain elementary steps, creating nonequilibrium energy distributions among various reaction pathways. However, quantitative studies validating these hypotheses on metal nanoparticle surfaces are lacking. We examine the influence of continuous wave visible photon fluxes on the CO desorption rates from 1 to 2 nm diameter Pt and Pd nanoparticle surfaces supported on γ-Al2O3. Temperature-programmed desorption measurements quantified via diffuse reflectance infrared Fourier transform spectroscopy demonstrate that visible photon fluxes significantly enhanced the rate of CO desorption from Pt nanoparticles in a wavelength-dependent manner. 440 nm photons most efficiently promoted CO desorption from Pt nanoparticle surfaces, aligning with the excitation energy for the interfacial electronic transition within the Pt-CO bond. Conversely, visible photon fluxes had no measurable influence on CO desorption rates from Pd nanoparticle surfaces after accounting for photon-induced heating. Density functional theory calculations demonstrate that the Pt-CO bond exhibits a narrower LUMO resonance, stronger coupling between the photoexcitation and forces induced on the metal-C bond, and vibrational energy dissipation that more effectively couples to desorption as compared to Pd-CO. These results demonstrate the specificity photons provide in facilitating chemical reactions on metal nanoparticle surfaces and substantiate the idea that photon fluxes can steer processes and outcomes of catalytic reactions in ways not achievable by equilibrium heating.

Patients' Experience to MRI Examinations-A Systematic Qualitative Review With Meta-Synthesis.

BACKGROUND: Patients often mention distress, anxiety, or claustrophobia related to MRI, resulting in no-shows, disturbances of the workflow, and lasting psychological effects. Patients' experience varies and is moderated by socio-demographic aspects alongside the clinical condition. While qualitative studies help understand individuals' experiences, to date a systematic review and aggregation of MRI individuals' experience is lacking. PURPOSE: To investigate how adult patients experience MRI, and the characterizing factors. STUDY TYPE: Systematic review with meta-aggregation and meta-synthesis. POPULATION: 220 patients' reported experience of adults undergoing clinical MRI and 144 quotes from eight qualitative studies. ASSESSMENT: Systematic search in PubMed, Scopus, Web of Science, and PsycInfo databases according to the PRISMA guidelines. For quality appraisal, the Joanna Briggs Institute (JBI) tools were used. Convergent segregated approach was undertaken. DATA ANALYSIS: Participant recruitment, setting of exploration, type of interview, and analysis extracted through Joana Briggs Qualitative Assessment and Review Instrument (JBI QARI) tool. Meta-synthesis was supported by a concept map. For meta-aggregation, direct patient quotes were extracted, findings grouped, themes and characterizing factors at each stage abstracted, and categories coded in two cycles. Frequency of statements was quantified. Interviews' raw data unavailability impeded computer-aided analysis. RESULTS: Eight articles out of 12,755 initial studies, 220 patients, were included. Meta-aggregation of 144 patient quotes answered: (1) experiences before, at the scanning table, during, and after an MRI, (2) differences based on clinical condition, and (3) characterizing factors, including coping strategies, look-and-feel of medical technology, interaction with professionals, and information. Seven publications lack participants' health literacy level, occupation, and eight studies lack developmental conditions, ethnicity, or country of origin. Six studies were conducted in university hospitals. DATA CONCLUSION: Aggregation of patients' quotes provide a foundational description of adult patients' MRI experience across the stages of an MRI process. Insufficient raw data of individual quotes and limited socio-demographic diversity may constrain the understanding of individual experience and characterizing factors. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

Overview of biosimilar medicines in Spain: market dynamics, policies, evidence-based insights and avenues for a sustainable market.

INTRODUCTION: After 17 years on the market, biosimilar medicines have contributed significantly to the sustainability of healthcare in Spain, providing cost-effective treatment options and savings of more than €1 billion by 2022 alone. To fully exploit this potential and meet the European pharmaceutical strategy's objectives of increased access and a resilient supply chain, Member States need to optimize their biosimilars policies. AREAS COVERED: We conducted an exhaustive review of biosimilar medicines in Spain, first describing their regulatory framework. Biosimilar policies at both national and regional level have been collected and updated figures on the biosimilars market are provided based on official data. Knowledge and acceptance of biosimilar medicines among patients and medical societies based on biosimilar positioning documents is reviewed. National evidence on the contribution of biosimilars to savings and sustainability is also included in this study. EXPERT OPINION: In Spain, there is a need to further build confidence in biosimilars, develop a strong national biosimilars policy and address regional variability, improve public procurement and adapt clinical practice guidelines following the commercialization of biosimilars. By implementing a holistic and evidence-based policy, Spain can fully exploit the benefits of biosimilar medicines and ensure better and equitable access across the healthcare system.

Effects of a passive upper-body exoskeleton on whole-body kinematics, leg muscle activity, and discomfort during a carrying task.

OBJECTIVE: To compare whole-body kinematics, leg muscle activity, and discomfort while performing a 10-min carrying task with and without a passive upper-body exoskeleton (CarrySuitⓇ), for both males and females. BACKGROUND: Diverse commercial passive exoskeletons have appeared on the market claiming to assist lifting or carrying task. However, evidence of their impact on kinematics, muscle activity, and discomfort while performing these tasks are necessary to determine their benefits and/or limitations. METHOD: Sixteen females and fourteen males carried a 15kg load with and without a passive exoskeleton during 10-min over a round trip route, in two non-consecutive days. Whole-body kinematics and leg muscle activity were evaluated for each condition. In addition, leg discomfort ratings were quantified before and immediately after the task. RESULTS: The gastrocnemius and vastus lateralis muscle activity remained constant over the task with the exoskeleton. Without the exoskeleton a small decrease of gastrocnemius median activation was observed regardless of sex, and a small increase in static vastus lateralis activation was observed only for females. Several differences in sagittal, frontal, and transverse movements' ranges of motion were found between conditions and over the task. With the exoskeleton, ROM in the sagittal plane increased over time for the right ankle and pelvis for both sexes, and knees for males only. Thorax ROMs in the three planes were higher for females only when using the exoskeleton. Leg discomfort was lower with the exoskeleton than without. CONCLUSION: The results revealed a positive impact on range of motion, leg muscle activity, and discomfort of the tested exoskeleton.

Limited Health Literacy Among Patients With Orthopedic Injuries: A Cross-sectional Survey of Patients Who Underwent Orthopedic Trauma Surgery in a County Hospital Setting.

BACKGROUND: Patients with limited health literacy have difficulty understanding their injuries and postoperative treatment, which can negatively affect their outcomes. MATERIALS AND METHODS: This cross-sectional questionnaire-based study of 103 adult patients sought to quantify patients' health literacy at a single county hospital's orthopedic trauma clinic and to examine their ability to understand injuries and treatment plans. Demographics, Newest Vital Sign (NVS) health literacy assessment, and knowledge scores were used to assess patients' comprehension of their injuries and treatment plan. Patients were grouped by NVS score (NVS <4: limited health literacy). Fisher's exact tests and t tests were used to compare demographic and comprehension scores. Multivariate logistic regression analysis was used to examine the association among low health literacy, sociodemographic variables, and knowledge scores. RESULTS: Of the 103 patients, 75% were determined to have limited health literacy. Patients younger than 30 years were more likely to have adequate literacy (50% vs 23%, P=.01). Patients who spoke Spanish as their primary language were 8.77 times more likely to have limited health literacy with respect to sociodemographic factors (odds ratio, 8.77; 95% CI, 1.03-76.92; P=.04). Low health literacy was 3.52 and 4.14 times more likely to predict discordance in answers to specific bone fractures and the narcotics prescribed (P=.04 and P=.02, respectively). CONCLUSION: Spanish-speaking patients have demonstrated limited health literacy and difficulty understanding their injuries and postoperative treatment plans compared with English-speaking patients. Patients with low health literacy are more likely to be unsure regarding which bone they fractured or their prescribed opiates. [Orthopedics. 2024;47(4):249-255.].

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Unmasking Obstruction in Hypertrophic Cardiomyopathy With Postprandial Resting and Treadmill Stress Echocardiography.

BACKGROUND: Latent left ventricular outflow tract obstruction (LVOTO) is an important cause of symptoms in patients with hypertrophic cardiomyopathy (HCM) but can be challenging to provoke. OBJECTIVES AND METHODS: To examine the value of postprandial resting and stress echocardiography and utilization of invasive or enhanced drug therapies (surgical myectomy, alcohol septal ablation, disopyramide, and mavacamten) in patients with postprandial LVOTO. Consecutive HCM patients without LVOTO underwent routine and postprandial echocardiography at rest, with provocation (Valsalva and standing) and after symptom-limited treadmill stress. RESULTS: Among 252 patients (mean age, 58 years, 39% women), postprandial LVOT gradients were higher compared with routine echocardiography at rest (median, 9.0 [0-38.0] vs 0 [0-14.0] mm Hg; P < .0001) and with provocation (18.5 [0-70.3] vs 1.5 [0-41.0] mm Hg; P < .0001). Postprandial exercise stress echocardiogram (PPXSE) gradients were higher in a subset of 44 patients who underwent both postprandial and fasting stress echocardiography (47.0 [5.3-81.0] vs 17.5 [0-46.0] mm Hg; P < .0001). In total, 49 (19.5%) patients achieved the ≥50 mm Hg threshold under routine conditions (rest/provocation); 90 (35.7%) additional patients achieved postprandial gradients ≥50 mm Hg (rest/provocation/exercise), 38 (15.1%) with PPXSE alone. A total of 71 patients were treated with 91 invasive or enhanced drug therapies, 32 (45.1%) of whom had gradients ≥50 mm Hg only after eating (rest/provocation) and 8 (11.3%) only with PPXSE, with symptom relief in the majority. CONCLUSIONS: Postprandial echocardiography was useful at unmasking LVOTO in more than one-third of patients who did not have high gradients otherwise. Eating before echocardiography is a powerful provocative tool in the evaluation of patients with HCM.

Emotional Intelligence and Perceived Social Support: Its Relationship with Subjective Well-Being.

The well-being of people is a key aspect of the field of psychology. Hence, it is important to analyse the variables that are related to life satisfaction and happiness as perceived by individuals and that, therefore, increase their overall well-being. The main objective of this study was to analyse the predictive capacity of emotional intelligence and perceived social support on both the level of life satisfaction and perceived happiness. A total of 380 psychology students completed the Trait Meta Mood Scale, the Multidimensional Scale of Perceived Social Support, the Satisfaction with Life Scale, and the Subjective Happiness Scale. The results show that both emotional intelligence and social support are related to and predictive of subjective happiness and life satisfaction. The importance of developing the components of emotional intelligence and promoting an adequate social network in young people is highlighted.

In Vivo Predictive Dissolution and Biopharmaceutic-Based In Silico Model to Explain Bioequivalence Results of Valsartan, a Biopharmaceutics Classification System Class IV Drug.

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) (Co-Diovan® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro-in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro-in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds.

Pharmaceutical Compounding in Veterinary Medicine: Suspension of Itraconazole.

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and ß-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.

Advancing patient-centered research practices in a pragmatic patient-level randomized clinical trial: A thematic analysis of stakeholder engagement in Emergency Medicine Palliative Care Access (EMPallA).

BACKGROUND: Involving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. METHODS: A SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration. RESULTS: The SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients. CONCLUSIONS: Our study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03325985, 10/30/2017.

Clinical research should involve patient and community stakeholder perspectives to make sure the study addresses questions important to the studied population. One way to do this is by creating a group of stakeholders who can advise on the conduct of a study. We assembled a Study Advisory Committee (SAC) for the Emergency Medicine Palliative Care Access (EMPallA) trial. The purpose of this clinical trial is to compare the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. This paper describes how the SACs involvement translated into direct impacts on the EMPallA trial. The trial research team held regular meetings with the SAC throughout the trial process. Their involvement led to many significant changes in the trial, such as  expanding recruitment inclusion criteria (Spanish-speaking patients), and including survey instruments to measure lonelines and caregiver burden. The SAC also devised strategies to overcome patient and caregiver recruitment and retention challenges, including the creation of patient-friendly materials and training for research coordinators. This study provides a successful example of how actively engaging patient and community stakeholders, through committee engagement, can promote patient priorities in all phases of a trial while facilitating patient recruitment and retention.

Contaminación ambiental por ruido / Environmental contamination caused by noise

Los sonidos indeseados constituyen el estorbo público más generalizado en la sociedad actual. La contaminación sonora, representa un problema ambiental para el hombre por las afectaciones a la salud que pueden ocasionar, los peligros por ruido actualmente están identificados como un gran problema a resolver por la salud ambiental, son las formas de energía potencialmente nocivas en el ambiente, que pueden resultar en peligrosidad inmediata o gradual de adquirir un daño cuando se transfiere en cantidades suficientes a individuos expuestos. La liberación de energía física puede ser súbita y no controlada, como el caso de un ruido fuerte explosivo o mantenido y más o menos bajo control como en las condiciones de trabajo con la exposición a largo plazo a niveles inferiores de ruido constante. Con la vigencia de la actualización de los lineamientos de la política económica y social del partido y la Revolución para el período 2016-2021, los autores se han motivado a incursionar en la problemática haciendo una valoración del ruido como uno de los ejemplos más comunes de peligro físico que ocasiona efectos en la salud (AU).

Unwanted sounds are the most generalized public hindrance in the current society. Sound contamination is an environmental problem for people because of the health disorders it could cause. Dangers by noise are nowadays identified as a big problem to solve for the environmental health because they are the forms of energy potentially noxious in the environment that could result in an immediate or gradual risk of causing damage when they are transferred to the exposed individuals in enough quantity. The physical energy release could be unexpected and non-controlled as in the case of a strong explosive noise, or sustained and more or less under control as in working conditions with the long-term exposition to lower levels of constant noise. In force of the Party and Revolution social and economic politics up-dating for the period 2016-2021, the authors have been motivated to deal with this problem, stating that noise is one of the most common examples of physical danger causing effects on human health (AU).

Influencia de los contaminantes atmosféricos sobre la salud / Atmospheric contaminants influence on health

El crecimiento urbano e industrial de las últimas décadas ha ocasionado un aumento de la contaminación atmosférica y por tanto un mayor riesgo para la salud. La mayoría de los contaminantes atmosféricos producen efectos perjudiciales en función de su concentración, por lo que se hace necesario identificar su existencia y el control de los niveles de cada uno de estos elementos potencialmente peligrosos. La contaminación atmosférica es un problema que afecta por igual a países desarrollados y en desarrollo. Las fuentes principales de contaminación de origen humano son el transporte, la producción de energía y las actividades industriales, así como los compuestos inorgánicos gaseosos, que son extremadamente peligrosos para la salud de la población. La contaminación atmosférica por diferentes sustancias químicas presenta en la actualidad, una gran connotación en el mundo entero, dado los efectos nocivos sobre los ecosistemas y en particular, sobre la salud humana y materiales metálicos. El desarrollo urbano, la modificación de la superficie de la tierra y el cambio climático son fenómenos derivados de una explosión demográfica mundial y están alterando la composición del aire lo que perjudica no solamente a las personas, sino también, a los animales y las plantas del ecosistema. Es por eso que el objetivo del trabajo consiste fue identificar los principales contaminantes atmosféricos y las fuentes antropogénicas que causan desviaciones a la salud (AU).

The industrial and urban growth of the last decades has caused an increment of the atmospheric contamination, and therefore a higher risk for health. Most of the atmospheric contaminants produce harmful effects in dependence of their concentration, so it is necessary to identify their existence and to control the levels of each of these potentially dangerous elements. Atmospheric contamination is a problem affecting both, the developed and developing countries in the same way. The main human-originated contamination sources are transportation means, energy production and industrial activities, and also the gaseous inorganic compounds that are extremely dangerous for the population's health. Atmospheric contamination caused by different chemical substances has currently a great connotation around the world, due to the noxious effects on the ecosystems and particularly on the human health and on the metallic materials. The urban development, the modification of the earth surface and the climatic change are phenomena derived from a world demographic explosion that are harming not only people but also the ecosystem´s animals and plants. That is why the objective of the work was to identify the main atmospheric contaminants and the anthropogenic sources causing health deviations (AU).

Molecular diagnosis of dengue virus infections in samples collected on filter paper / Diagnóstico molecular de infecciones por virus Dengue en muestras colectadas en papel de filtro

Dengue virus infections (DENV) are a severe public health problem due to the high rates of morbidity and mortality involved, and the fact that no clinical treatment or vaccines are available. In order to strengthen the laboratory diagnosis for surveillance systems in tropical countries with low resources, we report an optimized method using filter paper for blood spotting and subsequent molecular diagnosis of DENV serotypes. Control strains of all serotypes, as well as 35 whole blood patient samples dispensed on filter paper, were stored at room temperature for as long as 36 months. RT-PCR of 5’UTR-C fragment was amplified through adapted protocols to diagnose all dengue serotypes. Results showed amplification for all four viral serotypes, including control viral strains and 88.6 % of the samples. These results allowed determining the utility of filter paper for the preservation of samples regularly obtained from patients with clinical suspicion of dengue in settings where low resources do not permit an immediate analysis of the samples. Likewise, this study evidence the possibility of molecular diagnosis of DENV from multiple areas of the world where there are no laboratories with the capacity to confirm DENV cases.

Las infecciones por virus Dengue (DENV) representan un grave problema de salud pública debido a las altas tasas de morbilidad y mortalidad que causan, además no cuentan con tratamiento clínico específico, ni vacuna. Con el fin de reforzar el diagnóstico de laboratorio para los sistemas de vigilancia epidemiológica en países tropicales con recursos económicos limitados, se optimizó una metodología utilizando papel de filtro para la recolección de muestras y el subsiguiente diagnóstico molecular de los serotipos de DENV. Se emplearon cepas controles correspondientes a todos los serotipos virales, así como 35 muestras de sangre total dispensadas en papel de filtro que fueron mantenidas a temperatura ambiente por 36 meses. Las muestras fueron analizadas mediante RT-PCR para la amplificación de la región del genoma correspondiente a 5´UTR-C de los DENV. Los resultados mostraron la amplificación de los mencionados fragmentos en 88,6% de las muestras analizadas, así como de las cepas controles. Estos resultados evidenciaron la utilidad del papel de filtro para conservación de muestras obtenidas de pacientes con sospecha clínica de dengue ubicados en zonas donde no es posible realizar análisis de laboratorio de forma inmediata, así como su uso para el diagnóstico molecular. De este modo se reforzaría la vigilancia en áreas, donde no hay laboratorios con capacidad para confirmar casos de DENV.

La sostenibilidad ambiental regional: una propuesta metodológica para su estudio más allá de la ecología urbana / Regional environmental sustainability: a methodoogical proposal for a study beyyond ubrban ecology

El sistema territorial a escala regional posee una mayor capacidad para permitir la disipación y asimilación de los diferentes impactos ambientales producidos en el sistema urbano. Los espacios urbanos considerados como los principales promotores de graves impactos ambientales, deben ser analizados como sistemas interdependientes de otros territorios, estableciéndose así, la conformación de sistemas regionales de gran importancia para el análisis de la capacidad de sostenibilidad ambiental. El método de estudio de dicha capacidad se convierte en el objetivo del presente artículo (fase cuatro de la metodología), cuyo producto es uno de los resultados de la investigación realizada en el marco de la tesis de maestría de una de las autoras. La selección de 22 variables ambientales estratégicas producto del análisis de dos grupos de variables ambientales estudiadas por la investigación, se convierten en las condicionantes principales que determinarán con mayor o menor éxito, la sostenibilidad ambiental de un territorio configurado como región.

The territorial system at a regional scale has a greater capacity to allow dissipation and assimilation of different environmental impacts produced in the urban system. Urban spaces, considered as the main promoters of serious environmental impacts, should be analyzed as interdependent systems of other territories, establishing this way the conformation of regional systems of great importance for analyzing the environmental sustainability capacity. The method of study of such capacity is the aim of this article (phase four of the methodology), which product is one of the results of the research conducted within the framework of the Master's Degree thesis requirement of one of the authors. The selection of Twenty-two strategic environmental variables resulting from the analysis of two groups of environmental variables studied within this research become the main determinants that will determine the degree of success of environmental sustainability of an area set up as a region.

Evaluación de los criterios diagnósticos-clínicos y anatomo patológicos en pacientes con micosis / Fungoides diagnostic criteria evaluation of the clinic anda anatomo pathology in patients with mycosis fungoides

Se realizó un estudio retrospectivo para evaluar cuáles eran las características clínicas y anatomo patológicas para el diagnóstico de los pacientes con micosis fungoides (MF) tratados en el servicio de dermatología del CES Sabaneta entre abril de 1997 y mayo de 2004. Además se buscaba describir las características sociodemográficas locales y contrastarlas con el perfil epidemiológico descrito en la literatura. Materiales y métodos: la muestra estuvo conformada por 43 casos con diagnóstico de MF a los que se les revisó la historia clínica y las placas histológicas fueron evaluadas por dos patólogos separadamente. Resultados: la edad media de los pacientes fue de 57,7 años, la mayoría fueron mujeres de fototipo II. El 58,1% presentó compromiso de la superficie corporal mayor al 11% y la lesión semiológica mas frecuente fue la placa. Las áreas mas afectadas fueron las extremidades inferiores luego la espalda, extremidades superiores y por último abdomen. Sólo 12 pacientes tenían un diagnóstico previo, el más frecuente fue la parapsoriasis de grandes placas. El 71% de los casos se diagnosticó en la primera biopsia. Los hallazgos histológicos más frecuentes entre los dos patólogos fueron: la presencia de infiltrado inflamatorio a nivel papilar y perivascular; epidermotropismo lineal y pagetoide; las microabscesos de Pautrier y la fibrosis de la dermis papilar. Al comparar los diagnósticos entre los dos patólogos, sólo los microabscesos de Pautrier mostraron concordancia.

A retrospective study was made to evaluate clinical characteristics and anatomic pathological for the diagnosis of patients with mycosis fungoides (MF) treated in the dermatology service of the CES Sabaneta from April 1997 until May 2004. In addition, a description of the local socio demographics characteristics were looked for and contrast them with the epidemiologist profile described in literature. Materials and methods: The sample was conformed by 43 cases with diagnose of MF, in which were review their clinical history and the histological plates were evaluated by two pathologists separately. Results: The average age of the patients was of 57, 7 years; the majority was women of phototype II. 58,1% had affected a greater corporal surface above 11% and the frequents semiologic injury was the plate. The more affected areas were the inferior extremities then the back, superior extremities and finally the abdomen. Just 12 patients had previous diagnosis; the most frequent was the parapsoriasis of great plates. In this study 71% of the cases were diagnosed in the first biopsy, the most frequent histologists findings made by the two pathologists were: the presence of infiltrated inflammatory at papillary level and perivascular, linear and pagetoid epidermotropism, the microabscesses of Pautrier and the fibrosis of the papillar dermis. When those findings were compared by the two pathologists through the index of Kappa with a confidence level of 95%, just the microabscesses of Pautrier showed agreement.

Correlación entre modelos in vitro, in situ e in vivo en estudios de absorción: [revisión] / In vitro, in situ and in vivo correlations in drug absorption: [review]

Predecir la magnitud y la velocidad de absorción de una sustancia es crucial en el diseño de medicamentos. En este campo se han empleado distintas metodologías, como modelos in vitro o ensayos in situ o in vivo en animales. Este trabajo analiza modelos matemáticos empleados para estudiar la absorción intestinal y analizar la influencia de tensioactivos en la permeabilidad intestinal; predecir la fracción de dosis absorbida; caracterizar parámetros de absorción pasiva y activa; y establecer correlaciones entre parámetros obtenidos in vitro e in situ. Cuanto más complejo es el modelo tanto mejor se correlaciona con los valores en humanos, pero resultan más difíciles de implementar. Los modelos in vitro resultan bastante adecuados para predecir la absorción cuando se produce por difusión pasiva, pero deficitarios cuando se produce por transporte activo. Se pone de manifiesto la necesidad de continuar desarrollando modelos que permitan el escalado a humanos...

Predicting drug rate and extent from the gastrointestinal tract is a key step in the process of new drug design and development. To predict oral absorption different approaches, like in vitro methods or in situ or in vivo animal experiments, have been used. We will analyse some of the mathematical models that have been applied: (a) to study intestinal drug absorption and the influence of surfactants on intestinal permeability, (b) to predict oral fraction absorbed, (c) to characterize active and passive transport parameters, and (d) correlations between in vitro and in situ results. More complex models lead to better correlations with human values, but these systems have a lower throughput, so there is a need to develop models that allow scaling up from the in vitro data. In vitro systems perform well for estimating passive diffusion absorption but more research is necessary with regard to carrier-mediated absorption processes...

Teniosis y cisticercosis en comerciantes de alimentos en mercados de una área de la ciudad de México / Taeniosis and cysticercosis in food traders in markets in México city

Con el objeto de conocer la prevalencia de teniosis y cisticercosis en comerciantes de alimentos de mercados de la Delegación política de Xochimilco de la Ciudad de México, se encuestaron 262 comerciantes de 11 mercados. En ellos se hicieron estudios coproparasi-toscopicos seriados y en la sangre se buscaron anticuerpos específicos contra cisticerco mediante inmunoelectrotransferencia. Sólo 115 entregaron las muestras fecales, y de ellas, en 110 se obtuvo la muestra de sangre. La seroprevalencia de anticuerpos para cisticercos fue del 0,9 per cent una muestra de material fecal se encontraron huevos de T. solium. Entre los comerciantes, 56,4 per cent algunos alimentos con carne de cerdo; 11,3 per cent de ellos criaban los cerdos en su casa y los sacrificaban de manera clandestina para vender su carne. Por lo tanto, los comerciantes de alimentos con carne de cerdo, que expenden sus productos en estos mercados, parecen estar rara vez expuestos a la T. solium.

Síndrome branquio-oto-renal / Branchio-oto-renal syndrome

El Síndrome Branquio-Oto-Renal es una entidad clínica heredada en forma autosómica dominante, caracterizada por la presencia de hipoacusia, malformaciones del oído, remanentes branquiales y displasia renal. Presentamos una familia afectada por el síndrome y una revisión de sus aspectos clínicos y genéticos