The secretome from human-derived mesenchymal stem cells augments the activity of antitumor plant extracts in vitro.

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

Economic recession, illicit drug use and the young population: a systematic literature review and meta-analysis.

AIMS: Economic recessions impact on drug use through different channels, with potential conflicting outcomes. Previous studies have reached mixed outcomes, and a clear and comprehensive picture is difficult to depict. METHODS: We use a systematic review of literature - conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines - and a hierarchical mixed-effects meta-analysis to provide a comprehensive quantitative assessment of the relationship between business cycle and the use of drugs by young populations. The heterogeneity of studies was assessed by the I2 statistic, and the publication bias was evaluated with contour-enhanced funnel plots. RESULTS: We identify 25 studies, published over the period 2008-2020. These articles carried out an empirical analysis of the impact of the business cycle on illegal drug consumption in Organisation for Economic Co-operation Development (OECD) countries. Most of the studies (17 studies) covered the 2007 financial crisis. Among the outcomes, 9 studies traced a countercyclical relationship between economic recessions and drug use, 3 showed a procyclical relationship and 13 studies found mixed results. Unemployment was the most widely used variable to assess macroeconomic conditions in most of the studies (21 studies). The meta-analysis shows a partial correlation of .03 (95% confidence interval (CI): .0147-.0453) between the unemployment rate and drug use among young individuals. Therefore, we conclude that, on average, recessions tend to boost drug use. This impact is more marked with cannabis use than it is with cocaine, opioids or other drugs. CONCLUSION: This study provides robust evidence that in periods of economic downturns, the young populations tend to increase the use of illegal drugs, with cannabis as their main preference. Therefore, in periods of economic severity, society may particularly benefit from implementing widely reaching public prevention programmes and demand reduction interventions, targeting this subgroup of the population.

The Envirome Web Service: Patient context at the point of care.

Patient context - the "envirome" - can have a significant impact on patient health. While envirome indicators are available through large scale public data sources, they are not provided in a format that can be easily accessed and interpreted at the point of care by healthcare providers with limited time during a patient encounter. We developed a clinical decision support tool to bring envirome indicators to the point of care in a large pediatric hospital system in the Kansas City region. The Envirome Web Service (EWS) securely geocodes patient addresses in real time to link their records with publicly available context data. End-users guided the design of the EWS, which presents summaries of patient context data in the electronic health record (EHR) without disrupting the provider workflow. Through surveys, focus groups, and a formal review by hospital staff, the EWS was deployed into production use, integrating publicly available data on food access with the hospital EHR. Evaluation of EWS usage during the 2020 calendar year shows that 1,034 providers viewed the EWS, with a total of 29,165 sessions. This suggests that the EWS was successfully integrated with the EHR and is highly visible. The results also indicate that 63 (6.1%) of the providers are regular users that opt to maintain the EWS in their custom workflows, logging more than 100 EWS sessions during the year. The vendor agnostic design of the EWS supports interoperability and makes it accessible to health systems with disparate EHR vendors.

The impact of socioeconomic position on non-communicable diseases: what do we know about it?

AIMS: Non-communicable diseases (NCDs) have become a primary health concern for most countries around the world. The aim of this research is to analyze the relevant evidence that determines the effect of socioeconomic position (SEP) on the incidence and prevalence of NCDs. METHODS: A systematic literature search was performed using PubMed, Cochrane Library, and Web of Science to identify evidence regarding the relationship between income inequalities and NCDs, between 2005 and 2015. The final selection of papers was based on applied studies focusing on Organisation for Economic Co-operation and Development (OECD) countries and articles referring to three main groups of chronic diseases: cardiovascular and heart diseases, cancer, and diabetes. RESULTS: A final set of 47 selected studies were fully taken into account in this review. Despite significant heterogeneity in exposure and outcomes measures, overall the evidence suggests that having low SEP increases the risk of developing cardiovascular diseases (CVDs), lung and breast cancer, and type 2 diabetes. SEP is also associated with multiple NCD risk factors such as smoking and physical inactivity. CONCLUSION: Low socioeconomic status appears to have a significant consistent impact on mortality and morbidity caused by NCDs in OECD countries. Social and economic disadvantages are associated with health inequalities in terms of access to care, increased incident risk of NCDs, and early death. These findings point to the need for public health strategies and research to address socioeconomic status disparity among individuals.

Bacteriological and histopathological analysis of Penaeus vannamei experimentally infected with Vibrio parahaemolyticus-AHPND strains.

Vibrio parahaemolyticus strains have been identified as the causative agent of acute hepatopancreas necrosis disease (Vp AHPND+) in shrimp. In the present work, a highly virulent (M0904) and less virulent (M0607) strain of Vp AHPND+ were used in experimental infections of Penaeus vannamei. Throughout the experiment, histopathological analyses were conducted on shrimp tissues, and samples from the bottom (B) and water column (WC) of each aquarium were taken to estimate bacterial growth. The first deaths of shrimp challenged with Vp M0904 occurred 4 h post-infection (hpi), reached 50% mortality at 17 hpi, and showed more acute pathological progression associated with AHPND despite both strains having similar bacterial densities from 0-4 hpi. The first deaths of shrimp inoculated with Vp M0607 occurred at 13 hpi, a difference of 9 h. These shrimps displayed reduction of reserve vacuoles in R and B cells of the hepatopancreas, and reached 50% mortality at 27 hpi. As bacterial growth in the WC and B in the first hours was similar for both strains, bacterial density was not a significant factor in Vp virulence. Since pirAB toxin is the causative agent of AHPND, it is possible that there is a threshold level at which the toxin damages hepatopancreatic tissues, so production or secretion of the toxin can be dependent of the Vp strain. We propose new AHPND stage: remission with 3 main routes for the disease outcome after the remission stage (re-infection, chronic effect and recuperation). Hepatopancreatic embryonic cells can be used as a biological indicator of this stage.

Physical restraint in critical care units from the experience of doctors and nursing assistants: In search of an interdisciplinary interpretation. / La contención mecánica en unidades de cuidados críticos desde la experiencia de los médicos y técnicos en cuidados auxiliares de enfermería: buscando una lectura interdisciplinar.

OBJECTIVES: The study aim was to explore the experience of doctors and nursing assistants in the management of physical restraint (PR) in critical care units. METHOD: A multicentre phenomenological study that included 14 critical care units (CCU) in Madrid (Spain). The CCU were stratified according to their use of physical restraint: "frequently used" versus "seldom used". Three focus groups were formed: the first comprised nursing assistants from CCUs that frequently used physical restraint, the second comprised nursing assistants from CCUs that seldom used physical constraint, and the final group comprised doctors from both CCU subtypes. Sampling method: purposive. DATA ANALYSIS: thematic content analysis. Data saturation was achieved. RESULTS: Four principle themes emerged: 1) concept of safety and risk (patient safety versus the safety of the professional), 2) types of restraint, 3) professional responsibilities (prescription, recording, and professional roles) and 4) "zero restraint" paradigm. The conceptualisation regarding the use of physical contentions shows differences in some of the principal themes, depending on the type of CCU, in terms of policies, use and management of physical constraint (frequently used versus seldom used). CONCLUSIONS: The real reduction in the use of physical restraint in CCU must be based on one crucial point: acceptance of the complexity of the phenomenon. The use of physical restraint observed in the different CCU is influenced by individual, group and organisational factors. These factors will determine how doctors and nursing assistants interpret safety and risk, the centre of care (patient or professional-centred care), the concept of restraint, professional responsibilities and interventions, interactions of the team and the leadership.

Relación entre la grasa corporal y la expresión de ira en personas que realizan ejercicio regularmente / Relacionamento entre gordura corporal e expressão de raiva em pessoas que se exercitam regularmente / Relationship between body fat mass and the expression of anger in people who practice exercise customarily

La actividad física proporciona beneficios, tanto a la población sana como enferma, pero también puede derivar en problemas psicológicos y emocionales como respuesta al estrés. Además, aquellos atletas con menor peso corporal presentan indicadores más elevados de depresión e ira. Se plantea determinar la relación de la grasa corporal sobre la expresión de ira y entender la relación entre distintos comportamientos psicológicos, en personas físicamente activas. 264 sujetos cumplimentaron el Inventario de Expresión de Ira Estado-Rasgo, versión 2, para el estudio sobre las características de la ira y sus efectos en la salud mental y física. Se tomaron medidas antropométricas (peso, talla, IMC, porcentaje de grasa corporal, masa libre de grasa). Se calcularon distintos percentiles en función del género y edad, clasificando a los participantes en tres grupos: percentil 55 de grasa corporal. Se analizaron distintos comportamientos en relación al STAXI-2 y a los distintos percentiles, pero sin encontrar diferencias significativas entre la ira y los tres grupos (AU)

Physical activity provides benefits, both to healthy as to ill population, but can also lead to psychological and emotional problems in response to stress. Furthermore, those athletes with lower body weight have higher indicators of depression and anger. We propose to relate body fat on the expression of anger and to understand the relationship between different psychological behaviors in physically active people. 264 subjects completed the Anger Expression Inventory State Trait version 2 (STAXI-2), which studies the characteristics of anger and its effects on mental and physical health. Anthropometric measurements (weight, height, BMI, percent body fat, fat-free mass) were taken. Various body fat percentiles, 55 were calculated according to gender and age, classifying participants into three percentile groups. Different behaviors were recorded in relation to STAXI-2 and percentiles, but with no significant differences between anger and those groups (AU)

A atividade física proporciona benefícios tanto para pessoas saudáveis como doentes, mas também pode levar a problemas psicológicos e emocionais, como resposta ao estresse. Além disso, os atletas com menor peso corporal têm indicadores mais altos de depressão e raiva. Prevê-se a determinar a influência da gordura corporal sobre a modulação do comportamento e entender a relação entre os vários comportamentos psicológicos entre as pessoas fisicamente ativas. 264 pessoas preencheram um questionário ad hoc, que incluiu Anger Expression Inventory State Trait version 2 (STAXI-2). Medidas antropométricas (peso, altura, IMC, percentual de gordura corporal, massa livre de gordura) foram tomadas. Vários percentis foram calculados por sexo e idade, classificando os participantes em três grupos: percentil 55 de gordura corporal. Diferentes comportamentos foram registrados em relação ao STAXI-2 e os vários percentis, mas sem diferenças significativas entre a raiva e os três grupos (AU)

Right ventricular performance using myocardial deformation imaging in infants with bronchopulmonary dysplasia.

OBJECTIVE: Right ventricular (RV) performance among infants with bronchopulmonary dysplasia (BPD) remains poorly understood. We tested the hypothesis that myocardial deformation imaging (MDI) strain and strain rate would allow for differentiation between infants with severe and milder forms of BPD, independent of tissue Doppler imaging (TDI) and superior to conventional echocardiographic measurements. STUDY DESIGN: Infants with various severities of BPD (11 with none or mild, 13 with moderate and 10 with severe) underwent conventional echocardiography, TDI and MDI assessments at >36 weeks of corrected gestational age. BPD severity grading was determined according to the National Institutes of Child Health and Disease workshop rating scale by physicians blinded to the echocardiogram results. Group data were compared with one-way analysis of variance or Kruskal-Wallis tests, with post hoc multiple comparisons. RESULTS: No differences in traditional echocardiographic parameters or TDI among the three BPD severity groups were observed; none of the infants had evidence of pulmonary hypertension. Using MDI, infants with severe BPD had lower peak global systolic strain than did infants with moderate BPD (P<0.01) or mild/none BPD (P<0.01). Early and late diastolic strain rate measurements were similar across the three groups. CONCLUSIONS: Among infants with severe forms of BPD, evidence of abnormal RV systolic function was detected with MDI, but not traditional echocardiographic or TDI measurements. Infants with severe forms of BPD may represent a particularly high-risk subgroup for decreased RV performance warranting cardiac surveillance. MDI should be considered as a method to quantitate RV function in this population.

Enmascaramiento clínico: una revisión de la literatura / Clinical masking: a literature review

Son diversos los métodos planteados para aplicar enmascaramiento, de esta forma es necesario revisar la literatura en búsqueda de consenso. Se revisaron críticamente los métodos utilizados y recomendados por la literatura y sociedades internacionales, en torno a la aplicación de enmascaramiento. Se consultó entre agosto y noviembre de 2015 en PUBMED, SciELO y Google Scholar por estudios acerca de métodos de enmascaramiento utilizados en audiometría. También se revisaron las guías de organizaciones internacionales y lo publicado en libros relacionados con el área de audiología. El método de "La Meseta" es el más referenciado, siendo modificado posteriormente. Existen variaciones en criterios de atenuación interaural, necesidad de enmascaramiento, enmascaramiento inicial, incrementos para obtener la meseta y niveles del efecto de oclusión. Se concluye que la literatura muestra diferencias al momento de decidir cuándo enmascarar y cómo hacerlo. No obstante, se puede establecer criterios comunes en relación a los niveles de atenuación interaural, cuándo enmascarar, valores de efecto de oclusión y metodología. El método de "La Meseta" sigue siendo el más recomendado. La modificación realizada por Yacullo es la más referenciada y recomendada en la literatura actual.

Adequate use of masking is key in the correct diagnosis of hearing loss. Various methods are suggested regarding the application of clinical masking, hence the need to review literature in order to reach a consensus. To critically review the specialized literature and international societies' recommendations regarding clinical masking. From August to November 2015, PUBMED, SciELO and Google Scholar articles on clinical masking methods used in tonal audiometries were consulted, as well as international organization guidelines, and literature in the area of Audiology. Hood's plateau method, later revised, received the most references. The modified versions consider the number of increments needed to determine the true threshold, and the occlusion effect. Optimized methods show the variations regarding interaural attenuation, need for masking, initial masking level, increments to reach "The Plateau", and the occlusion effect. Literature shows differences regarding when and how to use masking; however, common criteria can be established with reference to the levels of interaural attenuation, when to use masking, occlusion effect values and methodology. The plateau method proposed by Hood is still the most recommended. Yacullo's optimization is currently the one with the most references and recommendations in specialized literature.

Preparedness of pediatric residents for fellowship: a survey of US neonatal-perinatal fellowship program directors.

OBJECTIVE: To evaluate the preparedness of pediatric residents entering accredited neonatal-perinatal medicine (NPM) fellowships in the United States. STUDY DESIGN: A multi-domain, validated survey was distributed to Program Directors (PDs) of US NPM fellowship programs. The 47-item survey explored 5 domains: professionalism, independent practice, psychomotor ability, clinical evaluation, and academia. A systematic, qualitative analysis on free-text comments was also performed. RESULTS: Sixty-one PDs completed the survey, for a response rate of 62% (61/98). For entering fellows, PDs assessed performance in professionalism positively, including 76% as communicating effectively with parents and 90% treating residents/house-staff with respect. In contrast, most PDs rated performance in psychomotor abilities negatively, including 59% and 79% as deficient in bag-and-mask ventilation and neonatal endotracheal intubation, respectively. Although 62% of PDs assessed entering fellows positively for genuine interest in academic projects, fewer than 10% responded positively that entering fellows understood research protocol design, basic statistics, or were capable of writing a cohesive manuscript well. Thematic clustering of qualitative data revealed deficits in psychomotor ability and academia/scholarship. CONCLUSIONS: On the basis of the perspective of front line educators, graduating pediatric residents are underprepared for subspecialty fellowship training in NPM. To provide the best preparation for pediatric graduates who pursue advanced training, changes to residency education to address deficiencies in these important competencies are warranted.

[Therapeutic restraint management in Intensive Care Units: Phenomenological approach to nursing reality]. / Manejo de la inmovilización terapéutica en Unidades de Cuidados Críticos: aproximación fenomenológica a la realidad enfermera.

AIMS: To identify nursing experience on physical restraint management in Critical Care Units. To analyse similarities and differences in nursing experience on physical restraint management according to the clinical context that they are involved in. METHOD: A multicentre phenomenological study was carried out including 14 Critical Care Units in Madrid, classified according to physical restraint use: Common/systematic use, lacking/personalised use, and mixed use. Five focus groups (23 participants were selected following purposeful sampling) were convened, concluding in data saturation. Data analysis was focused on thematic content analysis following Colaizzi's method. FINDINGS: Six main themes: Physical restraint meaning in Critical Care Units, safety (self-retreat vital devices), contribution factors, feelings, alternatives, and pending issues. Although some themes are common to the 3 Critical Care Unit types, discourse differences are found as regards to indication, feelings, systematic use of pain and sedation measurement tools. CONCLUSIONS: In order to achieve real physical restraint reduction in Critical Care Units, it is necessary to have a deep understanding of restraints use in the specific clinical context. As self-retreat vital devices emerge as central concept, some interventions proposed in other settings could not be effective, requiring alternatives for critical care patients. Discourse variations laid out in the different Critical Care Unit types could highlight key items that determine the use and different attitudes towards physical restraint.

Profile of canine patient with esophageal foreign bodies / Perfil del paciente canino con cuerpos extraños esofágicos

Objective. Determine the profile of the canine patient with esophageal foreign bodies to identify risk factors associated with the foreign bodies. Materials and Methods. This is a retrospective study made by the Veterinary Hospital Clinic of the Universidad de Extremadura (VHC). Different factors were analyzed in dogs with an endoscopic diagnosis of esophageal foreign bodies. Results. This pathology was more commonly found in young adult dogs and in small breeds. This pathology was present for the first time in the Portuguese Warren Hound, which was also the breed with the highest risk. Conclusions. The results obtained in this investigation are in agreement with the previous description of a patient that presents esophageal foreign bodies. Also, the Portuguese Warren Hound was found to be predisposed to this problem, with a higher risk factor than other breeds previously mentioned in the literature. To prevent esophageal foreign bodies, dogs should be fed raw meat and bones, especially small breeds. This pathology should always be kept in mind in dogs with esophagitis symptomology regardless of age, although it is most common in young adult dogs.

Objetivo. Determinar el perfil del paciente canino que presenta cuerpos extraños esofágicos para identificar las características de riesgo al presentar esta entidad. Materiales y métodos. Este es un estudio retrospectivo realizado en el Hospital Clínico Veterinario de la Universidad de Extremadura (HCV). Se analizaron diferentes parámetros de los perros que presentaron un diagnóstico endoscópico de cuerpos extraños esofágicos. Resultados. Esta patología se presentó más comúnmente en perros adultos jóvenes y en pacientes de raza pequeña. Se presenta por primera vez al Podenco Portugués, el cual además representó la raza con mayor factor de riesgo. Conclusiones. Los resultados obtenidos en esta investigación concuerdan con lo descrito anteriormente en cuanto a las características del paciente con cuerpo extraño esofágico. Asimismo, se reporta el Podenco Portugués como predispuesto a esta entidad, con un factor de riesgo mayor al de otras razas anteriormente mencionadas en la literatura. Para prevenir los cuerpos extraños esofágicos, se debe alimentar con carne cruda y huesos a los perros, especialmente a los de raza pequeña. Siempre se debe tener en cuenta esta patología en los perros con sintomatología de enfermedad esofágica sin importar su edad, pues su presentación es más común en perros adultos jóvenes.

Genome-wide linkage analysis and tumoral characterization reveal heterogeneity in familial colorectal cancer type X.

BACKGROUND: Familial colorectal cancer type X (FCCTX) fulfils clinical criteria defining Lynch syndrome (LS), but is not related to germline mutations in DNA mismatch-repair genes. Its aetiology remains unexplained and there is little evidence of involvement of the common colorectal carcinogenetic pathways. We aimed to identify susceptibility loci and gain insights into carcinogenic pathways involved FCCTX tumour development. METHODS: We performed a linkage analysis in 22 FCCTX families. We also constructed a tissue microarray in order to define an immunohistochemical (IHC) profile for FCCTX tumours (N = 27) by comparing them to three other types of colorectal tumors: LS (N = 18), stable early-onset (N = 31) and other sporadic disease (N = 80). Additionally, we screened for BRAF/KRAS mutations and determined CpG island methylator phenotype (CIMP) status for all FCCTX tumours. RESULTS: We found suggestive evidence of linkage at four chromosomal regions; 2p24.3, 4q13.1, 4q31.21 and 12q21.2-q21.31. We screened genes in 12q21 and ruled out the implication of RASSF9 and NTS, good candidates due to their potential involvement in carcinogenesis and colorectal epithelium development. Based on IHC profiles FCCTX tumours did not form a single, exclusive cluster. They were clearly different from LS, but very similar to stable early onset tumours. The CIMP and chromosomal instability pathways were implicated in one-third and one-quarter of FCCTX cases, respectively. The remaining cases did not have alterations in any known carcinogenic pathways. CONCLUSIONS: Our results highlight the heterogeneity of FCCTX tumours and call into question the utility of using only clinical criteria to identify FCCTX cases.

Placental transfusion strategies in extremely preterm infants: the next piece of the puzzle.

Evidence is growing on the potential value of enhancing placental-fetal transfusion at birth, with recent endorsement of the practice by the World Health Organization and American College of Gynecologists. However, these recommendations provide clinicians with little guidance on the optimal practice among infants born extremely premature (<28 weeks gestation) and those requiring immediate resuscitation. The goals of this review are to: 1) provide rationale for better outcomes among extremely preterm infants following delayed cord clamping or umbilical cord "milking" than with immediate cord clamping; 2) describe clinical situations that warrant immediate cord clamping following delivery and explore the controversy regarding optimal cord clamping practice among extremely premature infants, including those requiring immediate resuscitation; 3) discuss the quality of evidence in this subgroup of infants; 4) consider areas for future research, with a focus on characterizing if placental-fetal transfusion affects the magnitude or timing of variables associated with physiological transition. The review provided herein suggests that delayed cord clamping or umbilical cord milking can be applied safely to infants born prior to 28 weeks gestation, but the lack of evidence on the best practice among infants born severely depressed and requiring immediate resuscitation, who comprise a greater proportion of infant deliveries at the lowest gestational ages, is recognized. Future studies using well-defined physiologic outcome measures are needed to understand the role of placental transfusion in premature infants' adaptations to extrauterine life.

Prevalence and molecular characterization of pertactin-deficient Bordetella pertussis in the United States.

Pertussis has shown a striking resurgence in the United States, with a return to record numbers of reported cases as last observed in the 1950s. Bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is losing pertactin in response to vaccine immunity. Screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 California pertussis outbreak, U.S. isolates from routine surveillance between 2010-2012, and isolates from the 2012 Washington pertussis outbreak) by conventional PCR and later by Western blotting and prn sequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481 in the prn gene (prnIS481 positive). The first prnIS481-positive isolate was found in 1994, and the next prnIS481-positive isolates were not detected until 2010. The prevalence of pertactin-deficient isolates increased substantially to more than 50% of collected isolates in 2012. Sequence analysis of pertactin-deficient isolates revealed various types of mutations in the prn gene, including two deletions, single nucleotide substitutions resulting in a stop codon, an inversion in the promoter, and a single nucleotide insertion resulting in a frameshift mutation. All but one mutation type were found in prn2 alleles. CDC 013 was a predominant pulsed-field gel electrophoresis (PFGE) profile in the pertactin-positive isolates (203/994) but was found in only 5% (16/306) of the pertactin-deficient isolates. Interestingly, PFGE profiles CDC 002 and CDC 237 represented 55% (167/306) of the identified pertactin-deficient isolates. These results indicate that there has been a recent dramatic increase in pertactin-deficient B. pertussis isolates throughout the United States.

A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia.

Truncating mutations in the AXIN2 gene, a key regulator of ß-catenin degradation in the Wnt pathway, have been reported in three families with gastrointestinal adenomatous polyposis and features of ectodermal dysplasia. However, the role of AXIN2 in familial adenomatous polyposis (FAP) syndrome is not completely understood. We performed an in-depth study of APC and MUTYH, and ruled out their implication in 23 FAP families. We then investigated the role of other genes involved in the Wnt pathway, including AXIN2, and identified a novel missense variant in AXIN2 in one family with attenuated FAP. Carriers of the variant exhibited a variable number of polyps but none showed any sign of ectodermal dysplasia. We have demonstrated the pathogenicity of this novel variant by establishing its low frequency in controls as well as by LOH analysis, a segregation study, and immunofluorescent staining of AXIN2 and ß-catenin proteins. This report expands the phenotype known to be related to AXIN2 alterations and raises the question of whether to screen AXIN2 in FAP cases negative for alterations in APC and MUTYH.

Desarrollo y validación del instrumento meduc-rx32, para la evaluación de docentes de programas de la especialidad de postítulo en radiología / Development and validation of the meduc-Rrx32 questionnaire, to evaluate teachers of postgraduate radiology programs

El objetivo de este estudio es desarrollar y validar una pauta para la evaluación del proceso de enseñanza clínica en radiología; Medicina Universidad Católica, Radiología 32 ítems (MEDUC-RX32). Se utilizó metodología mixta para el desarrollo del instrumento: dos entrevistas grupales (residentes y docentes) y una individual a un jefe de programa de radiología. Utilizando técnica Delfi modificada para lograr acuerdo, un panel de validez nacional evaluó la importancia de cada ítem. El panel Delfi refinó el instrumento de 88 a 32 ítems luego de dos rondas. La pauta final fue piloteada en 55 residentes del programa. El instrumento definitivo presenta alta confiabilidad (coeficiente alfa de Cronbach de 0,957). El promedio de las evaluaciones del desempeño de los docentes fue de 6,23 mas menos 0,8 (escala Likert 0 a 7) constituyéndose en una pauta válida y confiable para la evaluación de docentes de programas de la especialidad de radiología en países de habla hispana.

The objective of this study is to develop and validate a guideline for the evaluation of the clinical teaching process in radiology; Catholic University Medical School, Radiology 32 items (MEDUC-RX32). A mixed methodology was used for the development of the questionnaire; two interview groups (residents and faculty) and one individual to a radiology program head. Using a modified Delphi technique to reach an agreement, a national validity panel assessed the importance of each item. The Delphi panel refined the questionnaire from 88 to 32 items after two rounds. The final guideline was perfomed in 55 residents of the program. The final instrument shows high reliability (Cronbach's alpha coefficient of 0.957). The average performance evaluations of teachers was 6.23 ± 0.8 (Likert scale 0 to 7) becoming a valid and reliable guideline for teacher evaluation of programs in the specialty of radiology, in Spanish speaking countries.

Adherencia y desempeño auditivo en uso de audífonos en pacientes adultos hipoacúsicos atendidos en la Red de Salud UC / Hearing aids' adherence and performance in adults with hearing loss at Red de Salud UC

Introducción: La presbiacusia es un problema frecuente y con gran impacto en la calidad de vida. El uso de audífonos es la principal estrategia de tratamiento aunque se han descrito adherencia y desempeño auditivo subóptimos en la mayoría de los pacientes. Objetivo: Evaluar adherencia, desempeño auditivo subjetivo y satisfacción en adultos hipoacúsicos usuarios de audífono en la Red de Salud UC. Material y método: Estudio transversal descriptivo de seguimiento telefónico a 84 pacientes usuarios de audífono según criterio GES, atendidos entre agosto 2010-julio 2011. Además de preguntas acerca de conductas sobre el uso de los audífonos, el desempeño auditivo fue evaluado mediante encuesta validada ®Hearing Handicap Inventory for the Elderly-Screening (HHIES)¼, y la satisfacción con una nota subjetiva (1-7 puntos). Resultados: Se encuestaron 84 pacientes, edad promedio 74,6 años. El 48 por ciento de los pacientes ocupa su audífono 1 o más días a la semana, con una satisfacción en escala subjetiva (nota 1 a 7) de 5,4. El desempeño auditivo subjetivo fue de HHIEs 18 puntos (dificultad leve-moderada). Discusión: Uno de cada dos pacientes a quien se le indica y recibe un audífono no lo ocupa. A pesar de una adecuada implementación en la mayoría persiste una discapacidad auditiva subjetiva moderada (HHIEs), Nuestros hallazgos en adherencia y desempeño son semejantes a los descritos en la literatura nacional.

Introduction: Presbiacusy is a frequent problem with high impact in quality of life. Use of hearing aids is the main strategy of treatment, although low adherence and subjective performance has been described in most patients. Aim: Assess the adherence, subjective hearing performance and satisfaction of adult patients with hearing loss users of hearing aids from Red de Salud UC. Material and method: Cross sectional, descriptive, follow up study of 84 patients with hearing loss and indication of hearing aid use according to ®GES¼ criteria, evaluated between August 2010 and July 2011. Questions about behaviour on the use of hearing aid were done, subjective performance was evaluated trough the validated ®Hearing Handicap Inventory for the Elderly-Screening (HHIES)¼ and a satisfaction score (from 1 to 7). Results: 84 patients were surveyed 64.3 percent female and had a mean age of 74.6 years. 48 percent percent of patients used the hearing aid 1 or more days of the week, satisfaction (subjective scale from 1 to 7) was 5.4. The subjective hearing performance was HHIEs 18 points (mild-moderate impairment). Discussion: One out of two patients to whom a hearing aid is indicated is not using it. Although there is an adequate implementation, in most patients persists a moderate subjective impairment (HHIEs). Our findings of adherence and performance are similar to the described in the national literature.

Clinical and genetic characterization of classical forms of familial adenomatous polyposis: a Spanish population study.

BACKGROUND: Classical familial adenomatous polyposis (FAP) is characterized by the appearance of >100 colorectal adenomas. PATIENTS AND METHODS: We screened the APC and MUTYH genes for mutations and evaluated the genotype-phenotype correlation in 136 Spanish classical FAP families. RESULTS: APC/MUTYH mutations were detected in 107 families. Sixty-four distinct APC point mutations were detected in 95 families of which all were truncating mutations. A significant proportion (39.6%) had not been previously reported. Mutations were spread over the entire coding region and great rearrangements were identified in six families. Another six families exhibited biallelic MUTYH mutations. No APC or MUTYH mutations were detected in 29 families. These APC/MUTYH-negative families showed clinical differences with the APC-positive families. A poor correlation between phenotype and mutation site was observed. CONCLUSIONS: Our results highlight that a broad approach in the genetic study must be considered for classical FAP due to involvement of both APC and MUTYH and the heterogeneous spectrum of APC mutations observed in this Spanish population. The scarcely consistent genotype-phenotype correlation does not allow making specific recommendations regarding screening and management. Differences observed in APC/MUTYH-negative families may reflect a genetic basis other than mutations in APC and MUTYH genes for FAP predisposition.

Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury.

The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30min of global ischemia followed by 45min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1mg/ml/min for 10min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1alpha that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection.