Hydrogen Sulfide Adsorption Mechanism and Breakthrough Curves of Highly Stable Na-, Na-H-, Ca- and K-Mordenites.

Hydrogen sulfide (H2 S) is a hazardous gas found in natural gas and biogas, lethal over 100 ppm. When released into the atmosphere, it can turn into sulfur dioxide. One option to remove H2 S is using porous materials such as zeolites. Among them, mordenite stands out due to its channel structure, wide availability, and low cost. In this work, we evaluated the H2 S adsorption capacity of mordenite using a volumetric static method. The results show the adsorption capacity of H2 S in mordenite varies with the exchanged cation. The highest was measured in Na-mordenite (~4.08 mmol H2 S/g mordenite). The experimental breakthrough curves for this zeolite confirmed Langmuir-type adsorption and strong affinity between Na+ cations and H2 S. Despite this interaction, the XRD diffractograms of Na-mordenite show that the material retained its crystalline structure. More information about the differences in the amount of H2 S adsorbed in the zeolites caused by the change in exchanged cation was obtained by H2 S adsorption followed by FTIR spectroscopy. The spectra show differences in the position of the peaks related to the different adsorption modes of H2 S caused by a change in the polarizing power of the cations due to their charge and position inside the zeolite pores.

Closure of refractory gastrocutaneous fistula with endoscopically guided percutaneous suturing with the use of miniature biopsy forceps.

Video 1Closure of a refractory gastrocutaneous fistula with endoscopically guided percutaneous suturing with the use of miniature biopsy forceps.

Characteristics and Outcomes of Cancer Patients With Venous Thromboembolic Events After Treatment With Immune Checkpoint Inhibitors.

OBJECTIVE: This study aimed to describe the clinical characteristics and outcomes of patients with venous thromboembolism (VTE) after Immune checkpoint inhibitors (ICI), focusing on patients with gastrointestinal (GI) immune-related adverse events (irAE). METHODS: In this retrospective, single-center study, we report the clinical outcomes of adult cancer patients who developed a VTE within 2 years of ICI initiation. Patients were excluded if alternate causes of VTE were present apart from malignancy and cancer therapy. The cohort was classified into those with GI-irAE, non-GI-irAE, and no irAE. A control group with ICI exposure without irAE and VTE was selected for comparative analysis. RESULTS: Of all ICI-treated patients, 1891 (17.2%) were diagnosed with VTE. In all, 501 (4.6%) had no etiology for VTE aside from malignancy and cancer therapy. Of these, 137 patients were included and classified as: 44 GI-irAE, 42 non-GI-irAE, and 51 no irAE. Chemotherapy within 6 months of ICI therapy was associated with increased VTE risk. There was no difference in the clinical course between those exposed to chemotherapy versus ICI therapy alone, time from ICI initiation to VTE, and VTE type, recurrence, or related hospitalization. While there was no difference in VTE-related mortality, the GI-irAE group was associated with lower all-cause mortality and superior overall survival. CONCLUSION: Combined ICI and chemotherapy use increased VTE risk. There is a similar disease course of VTE after ICI exposure, regardless of other irAEs. Co-existing GI-irAE with VTE is associated with superior overall survival. Prospective studies are needed to evaluate the relationship between ICI therapy and VTE and irAE impact on VTE outcomes.

NGSEP 4: Efficient and accurate identification of orthogroups and whole-genome alignment.

Whole-genome alignment allows researchers to understand the genomic structure and variation among genomes. Approaches based on direct pairwise comparisons of DNA sequences require large computational capacities. As a consequence, pipelines combining tools for orthologous gene identification and synteny have been developed. In this manuscript, we present the latest functionalities implemented in NGSEP 4, to identify orthogroups and perform whole genome alignments. NGSEP implements functionalities for identification of clusters of homologus genes, synteny analysis and whole genome alignment. Our results showed that the NGSEP algorithm for orthogroups identification has competitive accuracy and efficiency in comparison to commonly used tools. The implementation also includes a visualization of the whole genome alignment based on synteny of the orthogroups that were identified, and a reconstruction of the pangenome based on frequencies of the orthogroups among the genomes. NGSEP 4 also includes a new graphical user interface based on the JavaFX technology. We expect that these new developments will be very useful for several studies in evolutionary biology and population genomics.

Many paths, one destination: mapping the movements of a kleptoparasitic spider on the host's web.

Kleptoparasitic spiders live and forage in the webs of other spiders. Using vibratory cues generated by the host spider during prey capture, they leave their resting positions in the upper peripheries of the host web and move towards the centre of the web where they feed along with the host spider or steal small pieces of prey. While the triggers for initiating the foraging raids are known, there is little information about the fine-scale trajectory dynamics in this model system. We mapped the movement of the kleptoparasite Argyrodes elevatus in the web of the host Trichonephila clavipes. We filmed the movement of the kleptoparasite spiders and quantified the trajectory shape, speed, heading directions and path revisitation. Our results show that kleptoparasitic spider movement is spatially structured, with higher levels of speed at the peripheries and slower in the centre of the web. We found a high level of variation in trajectory shapes between individuals. We found that the majority of heading orientations were away from the hub suggesting that detouring or repeated approaches are an essential component of kleptoparasite movement strategies. Our results of the revisitation rate also confirm this pattern, where locations close to the hub were revisited more often than in the periphery. The kleptoparasite-host spider system is a promising model to study fine-scale movement patterns in small bounded spaces.

A Culturally Adapted SMS Text Messaging Intervention to Promote Antiretroviral Therapy Adherence Among African Americans: Protocol for a Single-Arm Trial.

BACKGROUND: African Americans are disproportionally affected by HIV and have poorer rates of antiretroviral therapy (ART) adherence compared to other racial or ethnic groups in the United States. Factors associated with poor HIV disease outcomes are commonly associated with sociostructural barriers that prevent engagement with and retention in HIV care. SMS text messaging interventions to promote ART adherence among predominantly non-Hispanic White persons with HIV (PWH) have been shown to be efficacious; however, limited research has been devoted to culturally tailoring interventions for underrepresented racial/ethnic groups. Considering African Americans show poorer engagement along the HIV care continuum, we developed an individualized and culturally tailored two-way SMS text messaging intervention to improve ART adherence and associated virologic suppression among African American PWH. OBJECTIVE: In this paper we describe the protocol of a culturally tailored individualized Texting for Adherence Building (iTAB) intervention in a 24- to 48-week, single-arm study. METHODS: We developed a culturally tailored iTAB intervention, which we are implementing in a 24- to 48-week, single-arm study. Participants were recruited from the Family Health Centers of San Diego (FHCSD), a federally qualified health center. Patient inclusion criteria were (1) receiving care at the FHCSD, (2) living with HIV, (3) self-identification as Black, African American, or of African ancestry, (4) English speaking, (5) age 18 or older, (6) currently on ART, and (7) able to provide informed consent. Study enrollment began in November 2017 and closed in July 2019. A total of 90 participants from the FHCSD enrolled in the iTAB intervention, and we anticipate completing data collection in July 2020. Participants were assisted in individualizing and customizing their SMS text message preferences at the baseline study visit. Self-assessment measures are collected at baseline, interim, and final study visits. Problems related to sending/receiving SMS text messages and barriers to ART adherence are assessed at each interim study visit. The FHCSD staff monitors and tracks participants' daily SMS text message responses to ART adherence reminders using a clinical dashboard. RESULTS: We hypothesize that the proportion of individuals achieving HIV virologic suppression (viral load <40 copies/mL) will be greater at the end of the intervention period compared to the proportion prior to study implementation. Additionally, we anticipate that rates of virologic suppression at the end of the intervention among participants receiving iTAB will be comparable to those among the general FHCSD non-African American population who did not receive iTAB. Finally, we anticipate a high response rate to iTAB SMS text messages as well as positive participant feedback at the end of the intervention with regard to the acceptability of, satisfaction with, and perceived efficacy of iTAB. CONCLUSIONS: The iTAB intervention is a novel individualized two-way SMS text messaging intervention that has been culturally tailored for use among African Americans with HIV. We anticipate that iTAB will demonstrate efficacy in future randomized control trials and will be supportive of medication adherence among other populations facing health disparities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21592.

Tailoring a mobile health text-messaging intervention to promote antiretroviral therapy adherence among African Americans: A qualitative study.

African Americans are disproportionately affected by HIV and socio-structural barriers that impact antiretroviral (ART) adherence. Two-way text-messaging interventions have shown promise in supporting adherence in US studies of mostly White people living with HIV (PLWH). However, culturally-appropriate tailoring is necessary to maximize intervention effectiveness among other racial/ethnic groups. Thus, to refine an existing text-messaging intervention, we examined barriers and facilitators to ART adherence among African Americans and perspectives on features to integrate into the extant intervention. Three focus groups, two with African American PLWH (n = 5 and n = 7) and one with providers of care (n = 11) were conducted; transcripts of audio-recordings were thematically analyzed. Adherence supports operated at individual, interpersonal, and structural/environmental levels (e.g., using reminders and pill organizers, wanting to protect partners from HIV, and positive interactions with providers). Adherence barriers also operated at multiple ecological levels (e.g., poor mental health, fear of disclosure of HIV status, and unstable housing). Participant-suggested features for refinement included: i) matching content to participants' comfort with receiving messages referencing HIV or medication-taking, ii) culturally-tailoring content for African Americans, iii) tracking adherence, and iv) encouraging adherence interactions between patients and providers. Feedback from both patients and providers is foundational to designing effective ART interventions among African American PLWH.

Aflatoxin M1 Determination in Infant Formulae Distributed in Monterrey, Mexico.

The occurrence of aflatoxin M1 (AFM1) in infant formulae commercialized in the metropolitan area of Monterrey (Nuevo León, Mexico) was determined by using immunoaffinity column clean-up followed by HPLC determination with fluorimetric detection. For this, 55 infant formula powders were classified in two groups, starter (49 samples) and follow-on (6 samples) formulae. Eleven of the evaluated samples (20%) presented values above the permissible limit set by the European Union for infant formulae (25 ng/L), ranging from 40 to 450 ng/L. The estimated daily intake (EDI) for AFM1 was determined employing the average body weight (bw) of the groups of age in the ranges of 0-6 and 6-12 months, and 1-2 years. The results evidenced high intake values, ranging from 1.56 to 14 ng/kg bw/day, depending on the group. Finally, with the EDI value, the carcinogenic risk index was determined, presenting a high risk for all the evaluated groups. Based on these results, it is a necessary extra effort by the regulatory agencies to reduce the AFM1 presence in infant formulae consumed in Mexico.

Trust in Physicians and Regional Brain Volumes: A Population-Based Study.

OBJECTIVE: Trust, a fundamental part of human interpersonal relationships, is known to be associated with specific brain regions and demographic characteristics. Level of trust in medical professionals can alter population health outcomes and influence the nature of the doctor-patient relationship. This study utilized structural magnetic resonance imaging (MRI) and trust data from the Dallas Heart Study (DHS), a large community-based study, to determine brain regions associated with degree of trust in physicians and the medical profession. The first phase of the DHS was conducted from 2000 to 2002 and the second phase from 2007 to 2009. METHODS: The MRI data were analyzed as part of the DHS using automated FreeSurfer software. Forward stepwise binary logistic regression was performed to investigate the association between measures of trust and bilateral brain region volumes and thickness followed by confirmatory multiple regressions of significant brain regions. A total of 1,596 participants were included in the final analysis. RESULTS: Left caudal anterior cingulate cortex (ACC) thickness was inversely correlated with trust of physicians (P < .01). There were no significant associations between trust in physicians and age, race or ethnicity, or education. CONCLUSIONS: The ACC is an integral part of the salience network, the brain network responsible for communication and social behavior. Trust in physicians did not appear to be influenced by demographic characteristics. The findings suggest there are neuroanatomical correlates of trust in physicians.

Relationship between trust in neighbors and regional brain volumes in a population-based study.

Trust is a fundamental part of human interpersonal relationships, and among other complex factors it is shown to be linked with demographic characteristics and specific regions of the brain. The authors utilized a large, community-based database gathered from the Dallas Heart Study to determine specific brain regions associated with an individual's trust in neighbors. A trust questionnaire was taken and regional brain volumes were determined from structural magnetic resonance imaging. Two analyses using logistic regressions in a training set and validation set were performed to investigate the association between measures of trust and bilateral brain region volumes and thickness. A total of 1527 participants were included in the final analysis. Right caudal anterior cingulate cortex thickness and left caudate volume were inversely correlated with neighbor trust, while left amygdala volume was positively correlated with neighbor trust. Greater age and higher level of education were positively correlated with neighbor trust. African Americans showed less neighbor trust than Caucasians and Hispanics. Anterior cingulate cortex, caudate, and amygdala are all integral parts of the salience network; thus, results of this study suggest that the salience network, the brain network responsible for functions such as communication and social behavior, may play a role in the formation of interpersonal trust.

Apuntes sobre el envejecimiento del sistema estomatognático. Revisión de la literatura / Notes on Aging of the Stomatognathic System. A Literature Review

El envejecimiento es un proceso natural de duración variable, homogéneo para cada especie. Es un proceso que depende del tiempo y consiste en un progresivo incremento de la vulnerabilidad y la disminución de la viabilidad del organismo. Para poder realizar un diagnóstico y tratamiento de los trastornos temporomandibulares, para entender su significado y aplicación, es necesario conocer los cambios que ocurren con la edad. Se realizó la presente revisión de la literatura para actualizar los aspectos principales del envejecimiento del sistema estomatognático. Se realizó una exploración en internet empleando motores de búsqueda especializados y utilizando descriptores relacionados con el tema, se consultaron bases de datos de salud. Se concluyó que las principales características de la articulación temporomandibular durante el envejecimiento se expresan en cambios degenerativos sin que esto apunte a manifestaciones clínicas, ni exista una relación lineal entre la edad y los cambios radiográficos de la morfología condilar, se sugiere que el envejecimiento muscular en el sistema estomatognático está relacionado con la reserva de células madres que parece agotarse con la edad, así como el remodelado vascular que ocurre con el envejecimiento, que puede ser el responsable de los cambios de la función muscular.

Aging is a natural process of varying length that occurs similarly in each species. It is a time-dependent process characterized by a progressive increase in the vulnerability and a decrease in the viability of the organism. It is necessary to know the age-related changes in order to diagnose and treat temporomandibular disorders. This literature review aims to provide an update of the main aspects related to aging of the stomatognathic system. An Internet search was conducted using specialized search engines and descriptors related to this subject. Health databases were also consulted. It was concluded that the main characteristics of the temporomandibular joint during aging are degenerative changes, without necessarily causing clinical manifestations and without a linear relationship between age and radiographic changes in condylar morphology. It is suggested that aging of the stomatognathic muscles is related to the depletion of the stem cell pool and the vascular remodeling that occurs with aging, which may be responsible for changes in muscle function.

Factores de riesgo de los trastornos temporomandibulares en el adulto mayor / Risk Factors for Temporomandibular Disorders in Older Adults

Son muy diversos los factores de riesgo de los trastornos temporomandibulares en el adulto mayor, por lo que debe hacerse un análisis pormenorizado de cada caso, para evaluar la posible concomitancia de varios de ellos, para darle el mayor peso al posible factor etiológico y prestar atención a los que se hagan perdurables o agravantes. Esta revisión bibliográfica tiene como objetivo actualizar el tema de los factores de riesgo de trastornos temporomandibulares en adultos mayores. Se realizó una búsqueda bibliográfica mediante motores de búsqueda especializados y descriptores relacionados al tema. Se concluyó que los factores psicológicos favorecen la aparición de dolor bucofacial crónico en el adulto mayor, además de que reducen sus capacidades para la rehabilitación. La oclusión, como causa de trastornos temporomandibulares, se manifiesta de diferentes formas para cada paciente. Es conveniente considerar las condiciones oclusales desde los puntos de vista estático y dinámico, antes de descartarla como factor desencadenante.

There are various risk factors for temporomandibular disorders in older patients. Consequently, a detailed analysis of each case should be performed in order to assess the possible concomitance of some of them, giving greater importance to the potential etiologic factor and paying attention to the lasting and aggravating factors. This literature review aims to update the information on risk factors for temporomandibular disorders in older adults. A literature search was performed using specialized search engines and descriptors related to the topic. It was concluded that psychological factors favor the development of chronic orofacial pain in older patients and reduce their capacity to rehabilitate. Occlusion, as the cause of temporomandibular disorders, presents itself in different ways in each patient. It is convenient to consider occlusal conditions from the static and dynamic point of view, before discarding occlusion as a triggering factor.

Gestión curricular de la carrera de Estomatología. Facultad de Estomatología de La Habana. 2008-2013 / Curricular management in the Dentistry career. Havana Dentistry Facultty. 2008-2013

Fundamento: la formación del estomatólogo requiere la gestión de la calidad del currículo concretada en un coherente y sistemático trabajo metodológico. Objetivo: exponer los resultados más representativos de la gestión curricular en la autoevaluación de la carrera de Estomatología con vistas a la evaluación externa. Métodos: se realizó un análisis descriptivo de la gestión curricular de la carrera de Estomatología en la Facultad "Raúl González Sánchez", de La Habana durante el período 2008-2013. Se utilizaron métodos teóricos, y como empírico el análisis documental. Se tuvieron en cuenta el criterio de expertos y los indicadores contenidos en el patrón de calidad del Sistema de Evaluación y Acreditación de Carreras Universitarias (SEA CU). Resultados: se muestra la coexistencia de dos planes de estudio: el C y el D, con una disciplina integradora, currículo propio y optativo, objetivos de año, disciplinas y asignaturas que garantizan el encargo social. Se cuenta con una estrategia educativa, y se seleccionó la estrategia curricular para la labor ética de los estudiantes como táctica principal de la carrera. Se destaca la importancia del componente laboral relacionado con lo docente y lo investigativo, en los distintos escenarios, desde el primer año de la carrera. Conclusiones: la correcta gestión curricular y los resultados favorables de la labor de los colectivos pedagógicos de la institución, dirigidos por profesores con categorías docentes principales y experiencia en su desempeño docente, han garantizado la calidad del proceso de formación de los estomatólogos.

Background: the formation of dentists requires the quality of the curriculum management that is attained through a coherent and systematic methodological work. Objective: to present the most representatives results of the curriculum management in the self assessment of the Dentistry career in view to the external assessment. Methods: a descriptive analysis of the curriculum management of the Dentistry career was carried out in Havana Dentistry Faculty from 2008 to 2013. Theoretical methods were used. Empirical methods: analysis of documents. Experts´ criteria were taken into account as well as the parameters of the quality pattern of the accreditation and assessment system for university careers. Results: it was shown that study plans C & D coexist in the career with an integrating discipline, proper and optional curriculum, the objectives of the year, disciplines and subjects which guarantee the social commitment. The career has an educative strategy, it was selected the curricular strategy for the ethical work with the students as the principal tactic of the career. It is stood out the importance of the working component in relation to the teaching and researching ones in the different scenarios, since the first year of the career. Conclusions: the correct curricular management and the favorable results of the work of the pedagogical staffs which are led by teachers with principal teaching ranks and experience in their performance have guaranteed the quality of the formation process of dentists.

Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect?

PURPOSE: Systemic exposure to rosuvastatin is approximately double that of Caucasians in Asian subjects. We investigated whether this pattern of increased exposure exists for other statins. METHODS: Plasma exposure following single-dose rosuvastatin 20 mg, atorvastatin 40 mg or simvastatin 40 mg was studied in Chinese, Japanese and Caucasian subjects. Plasma concentrations were determined using LC-MS methods. Impact of polymorphisms in SLCO1B1 (T521>C and A388>G) and in ABCG2 (C421>A) on exposure to rosuvastatin, atorvastatin, simvastatin and simvastatin acid was assessed. RESULTS: Relative to Caucasians, geometric mean area under the curve from time zero to time of last quantifiable concentration was 86 % (90 % confidence interval (CI), 51-130 %) and 55 % (26-91 %) higher for rosuvastatin in Chinese and Japanese subjects, respectively, 53 % (25-88 %) and 69 % (37-108 %) higher for atorvastatin, 23 % (0-52 %) and 12 % (-0.9-39 %) higher for simvastatin and 28 % (5-56 %) and 34 % (10-64 %) higher for simvastatin acid. Geometric mean maximum drug concentration was also proportionally higher for each statin. Polymorphisms in SLCO1B1 T521>C or ABCG2 C421>A were associated with higher exposure to rosuvastatin, atorvastatin and simvastatin acid (but not simvastatin) within a population, but only the ABCG2 C421>A polymorphism contributed towards between-population exposure differences. In individuals carrying wild-type alleles for both SLCO1B1 and ABCG2, area under the plasma concentration-time curve (AUC) still appeared to be higher for rosuvastatin, atorvastatin and simvastatin acid in Chinese and Japanese subjects compared with Caucasians, respectively. CONCLUSION: Increased exposure to statins in Asian subjects versus Caucasians may represent a more general class phenomenon than previously recognized.

Effect of CYP2C19 polymorphism on the pharmacokinetics of rosuvastatin in healthy Taiwanese subjects.

CYP2C19 contributes to N-desmethyl rosuvastatin formation in "in vitro" models. Approximately 80% of Taiwanese are CYP2C19 extensive metabolizers (EMs, CYP2C19*1/*1, *1/*2, or *1/*3). We studied the potential effect of CYP2C19 genotypes on rosuvastatin pharmacokinetics in healthy Taiwanese subjects following single and multiple daily oral doses of rosuvastatin calcium (20 mg). Geometric mean ratios for poor metabolizers (PMs): EMs for rosuvastatin were 0.974 and 0.872 for area under the curve and maximum plasma concentration on day 1 (1.01 and 0.965 on day 17) and for N-desmethyl rosuvastatin, 1.21 and 1.07 on day 1 (1.14 and 1.09 on day 17), respectively. Changes of lipid profiles from baseline to day 18 for PMs and EMs were -52.4% and -53.3% (low-density lipoprotein cholesterol), and -34.2% and -30.0% (total cholesterol), respectively. Rosuvastatin was generally well-tolerated by both PMs and EMs. These results suggest that CYP2C19 polymorphism does not affect rosuvastatin pharmacokinetics in healthy Taiwanese in a clinically meaningful way.

Gestión curricular de la carrera de Estomatología: Facultad de Estomatología de La Habana: 2008-2013 / Curricular management in the Dentistry career: Havana Dentistry Facultty, 2008-2013

Fundamento: la formación del estomatólogo requiere la gestión de la calidad del currículo concretada en un coherente y sistemático trabajo metodológico. Objetivo: exponer los resultados más representativos de la gestión curricular en la autoevaluación de la carrera de Estomatología con vistas a la evaluación externa. Métodos: se realizó un análisis descriptivo de la gestión curricular de la carrera de Estomatología en la Facultad Raúl González Sánchez, de La Habana durante el período 2008-2013. Se utilizaron métodos teóricos, y como empírico el análisis documental. Se tuvieron en cuenta el criterio de expertos y los indicadores contenidos en el patrón de calidad del Sistema de Evaluación y Acreditación de Carreras Universitarias (SEA CU). Resultado: se muestra la coexistencia de dos planes de estudio: el C y el D, con una disciplina integradora, currículo propio y optativo, objetivos de año, disciplinas y asignaturas que garantizan el encargo social. Se cuenta con una estrategia educativa, y se seleccionó la estrategia curricular para la labor ética de los estudiantes como táctica principal de la carrera. Se destaca la importancia del componente laboral relacionado con lo docente y lo investigativo, en los distintos escenarios, desde el primer año de la carrera. Conclusiones: la correcta gestión curricular y los resultados favorables de la labor de los colectivos pedagógicos de la institución, dirigidos por profesores con categorías docentes principales y experiencia en su desempeño docente, han garantizado la calidad del proceso de formación de los estomatólogos(AU)

Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study.

BACKGROUND: Pegvisomant is an effective treatment for acromegaly. OBJECTIVE: To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features. PATIENTS AND METHODS: Multicentre retrospective study involving 19 Spanish centres. RESULTS: Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02). CONCLUSIONS: A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.

Diseño y elaboración de la asignatura Rehabilitación soportada en las tecnologías de la informática y las comunicaciones (TICs) / Design and preparation of the subject Rehabilitation supported on the information and communications technologies (ICT)

Se describe el diseño y elaboración de la asignatura Rehabilitación I correspondiente al quinto semestre de la carrera de Estomatología soportada en las tecnologías de la informática y las comunicaciones. El trabajo se dividió en cinco etapas que comprendieron desde la selección y capacitación de los profesores hasta la terminación de todos los materiales en formato digital. Las principales ventajas en su aplicación están referidas a su extensión a todos los escenarios docentes del país y que privilegian el trabajo independiente de los estudiantes. Se constató un nivel de satisfacción considerable con los productos terminados, garantizando que los estudiantes reciban de forma uniforme los elementos fundamentales de la actividad y se integre de manera coherente al manejo de las tecnologías de la información y las comunicaciones(AU)

The design and the preparation of the subject called Rehabilitation I, which is taught at the 5th semester of the dentistry career and is supported on the information and the communications technologies, were described. The paper was divided into 5 phases, from the selection and training of professors to the finishing process of the digital materials. The main advantages lie in their extending to all the teaching settings of the country and in giving priority to the student's independent work. It was observed that the level of satisfaction with the end products was high, since they guarantee the equal access of the students to the fundamental elements of the subject and a coherent integration with the information and communication technologies management(AU)

Diseño y elaboración de la asignatura Rehabilitación soportada en las tecnologías de la informática y las comunicaciones (TICs) / Design and preparation of the subject Rehabilitation supported on the information and communications technologies (ICT)

Se describe el diseño y elaboración de la asignatura Rehabilitación I correspondiente al quinto semestre de la carrera de Estomatología soportada en las tecnologías de la informática y las comunicaciones. El trabajo se dividió en cinco etapas que comprendieron desde la selección y capacitación de los profesores hasta la terminación de todos los materiales en formato digital. Las principales ventajas en su aplicación están referidas a su extensión a todos los escenarios docentes del país y que privilegian el trabajo independiente de los estudiantes. Se constató un nivel de satisfacción considerable con los productos terminados, garantizando que los estudiantes reciban de forma uniforme los elementos fundamentales de la actividad y se integre de manera coherente al manejo de las tecnologías de la información y las comunicaciones

The design and the preparation of the subject called Rehabilitation I, which is taught at the 5th semester of the dentistry career and is supported on the information and the communications technologies, were described. The paper was divided into 5 phases, from the selection and training of professors to the finishing process of the digital materials. The main advantages lie in their extending to all the teaching settings of the country and in giving priority to the student's independent work. It was observed that the level of satisfaction with the end products was high, since they guarantee the equal access of the students to the fundamental elements of the subject and a coherent integration with the information and communication technologies management

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects.

AIM: Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban. METHOD: This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels - apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily- with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT). RESULTS: Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ~3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3-1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration-time profile. CONCLUSION: Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures.