The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model.

Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality in the pre-vaccine era and mouse models of pertussis pneumonia served in characterization of B. pertussis virulence mechanisms. However, the biologically most relevant catarrhal disease stage and B. pertussis transmission has not been adequately reproduced in adult mice due to limited proliferation of the human-adapted pathogen on murine nasopharyngeal mucosa. We used immunodeficient C57BL/6J MyD88 KO mice to achieve B. pertussis proliferation to human-like high counts of 108 viable bacteria per nasal cavity to elicit rhinosinusitis accompanied by robust shedding and transmission of B. pertussis bacteria to adult co-housed MyD88 KO mice. Experiments with a comprehensive set of B. pertussis mutants revealed that pertussis toxin, adenylate cyclase toxin-hemolysin, the T3SS effector BteA/BopC and several other known virulence factors were dispensable for nasal cavity infection and B. pertussis transmission in the immunocompromised MyD88 KO mice. In contrast, mutants lacking the filamentous hemagglutinin (FhaB) or fimbriae (Fim) adhesins infected the nasal cavity poorly, shed at low levels and failed to productively infect co-housed MyD88 KO or C57BL/6J mice. FhaB and fimbriae thus appear to play a critical role in B. pertussis transmission. The here-described novel murine model of B. pertussis-induced nasal catarrh opens the way to genetic dissection of host mechanisms involved in B. pertussis shedding and to validation of key bacterial transmission factors that ought to be targeted by future pertussis vaccines.

Selective Enhancement of the Cell-Permeabilizing Activity of Adenylate Cyclase Toxin Does Not Increase Virulence of Bordetella pertussis.

The whooping cough agent, Bordetella pertussis, secretes an adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) that catalyzes the conversion of intracellular ATP to cAMP and through its signaling annihilates the bactericidal activities of host sentinel phagocytes. In parallel, CyaA permeabilizes host cells by the formation of cation-selective membrane pores that account for the hemolytic activity of CyaA. The pore-forming activity contributes to the overall cytotoxic effect of CyaA in vitro, and it has previously been proposed to synergize with the cAMP-elevating activity in conferring full virulence on B. pertussis in the mouse model of pneumonic infection. CyaA primarily targets myeloid phagocytes through binding of their complement receptor 3 (CR3, integrin αMß2, or CD11b/CD18). However, with a reduced efficacy, the toxin can promiscuously penetrate and permeabilize the cell membrane of a variety of non-myeloid cells that lack CR3 on the cell surface, including airway epithelial cells or erythrocytes, and detectably intoxicates them by cAMP. Here, we used CyaA variants with strongly and selectively enhanced or reduced pore-forming activity that, at the same time, exhibited a full capacity to elevate cAMP concentrations in both CR3-expressing and CR3-non-expressing target cells. Using B. pertussis mutants secreting such CyaA variants, we show that a selective enhancement of the cell-permeabilizing activity of CyaA does not increase the overall virulence and lethality of pneumonic B. pertussis infection of mice any further. In turn, a reduction of the cell-permeabilizing activity of CyaA did not reduce B. pertussis virulence any importantly. These results suggest that the phagocyte-paralyzing cAMP-elevating capacity of CyaA prevails over the cell-permeabilizing activity of CyaA that appears to play an auxiliary role in the biological activity of the CyaA toxin in the course of B. pertussis infections in vivo.

[David Lynch - Eraserhead: The burtsing out from coercion - an art psychological approach].

David Lynch with his work 'Eraserhead' dove deep into the existential regions of the human psyche and brought back the product which he states to be 'his most spiritual film'. Three main factors (the psychobiography, the theories of psychoanalysis and the works of Lipot Szondi) helped me establish the theoretical fundament for the exploration of the trauma-induced state of coercion through the symbolism of the film. The established interrelations will give us a new perspective on Lynch's works and biography, and may give us a chance to take a closer look at the dynamics of the state coercion.

Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults.

PURPOSE: This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12-16 years [cohort 1a; n = 9]; 6-11 years [cohort 2; n = 8]; 4-5 years [cohort 3; n = 3]). METHODS: Model-based simulations were performed to guide dosing, especially in 1-5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20-60-mg tablet, cohorts 1a and 2; 0.66 mg/kg granule suspension, cohort 3). In cohort 1, gender-matched healthy adults (cohort 1b; n = 9) received AZL-M 80 mg. RESULTS: Exposure to AZL (active moiety of AZL-M), measured by dose-/body weight-normalized C max and AUC0-∞, was ∼15-30 % lower in pediatric subjects versus adults. In simulations, exposure with 0.66 mg/kg AZL-M in pediatric subjects weighing 8-25 kg approximated to AZL-M 40 mg (typical starting dose) in adults. The simulations suggest that 25-50-kg subjects require half the adult dose (10-40 mg), whereas 50-100-kg subjects can use the same dosing as adults. Adverse events were mild in intensity, apart from one moderate event (migraine). CONCLUSIONS: This dosing strategy should be safe in pediatric patients, as AZL exposure would not exceed that seen in adults with the highest approved AZL-M dose (80 mg).

Hierarchical spatio-temporal mapping of premature mortality due to alcoholic liver disease in Hungary, 2005-2010.

BACKGROUND: Excess alcohol consumption is a major public health issue in Hungary, with high mortality rates from alcohol disease. In addition, excess alcohol consumption has been found to differ by socioeconomic and environmental factors. METHODS: The spatial pattern of mortality from alcoholic liver disease across Hungary for the period 2005 and 2010, at municipality level, was investigated by sex using Bayesian modelling. The changes in mortality over this 6-year period were analysed using hierarchical spatio-temporal disease mapping. The association between the spatial distribution of mortality from alcoholic liver disease and cirrhosis and deprivation (by sex) was also assessed using a Hungarian-specific deprivation index. RESULTS: A statistically significant association was found between mortality and deprivation status in males. Areas of significantly highest age-adjusted relative risks were found, for males, in the south-western part, and at the eastern border of the country. A number of areas showed area-specific trends that were significantly steeper than the national average mortality trend. CONCLUSION: Using our findings, population groups with increasing mortality trends were identified, which may help decision makers fund effective health promotion programmes to reduce mortality rates in the working-age population.

Comparative analysis of health status and health service utilization patterns among rural and urban elderly populations in Hungary: a study on the challenges of unhealthy aging.

The demographic transition poses a significant challenge for health systems, especially in Central and Eastern European (CEE) countries, where the healthcare needs of aging populations are on the rise. This study aimed to describe and compare the health status and utilization of health services among the elderly residing in urban and rural areas of the most deprived region in Hungary. A comprehensive health survey was conducted in 2022, involving a randomly selected sample of 443 older adults (≥ 65 years) in Northeast Hungary. Multivariable logistic regression models adjusting for age, sex, education, financial status, chronic diseases, and activity limitations were used to investigate the association between type of residence and health service use. Among the study participants, 62.3% were female, 38.3% attained primary education, 12.5% reported a bad or very bad financial situation and 52.6% lived in urban areas. Overall, 24% of the elderly rated their health as very good or good (27.8% in urban and 19.7% in rural areas), while 57.8% (52.6% and 63.5% in urban and rural areas) reported limitations in daily activities. Compared to urban residents, rural residents reported lower rates of dentist visits (p = 0.006), specialist visits (p = 0.028), faecal occult blood testing (p < 0.001), colorectal cancer screening with colonoscopy (p = 0.014), and breast cancer screening (p = 0.035), and a higher rate of blood pressure measurement (p = 0.042). Multivariable models indicated that urban residence was positively associated with faecal occult blood testing (OR = 2.32, p = 0.014), but negatively associated with blood pressure (OR = 0.42, p = 0.017) and blood glucose measurements (OR = 0.48, p = 0.009). These findings highlight the influence of residence on health service utilization among older adults in Hungary. Further comprehensive studies are needed to better understand the health needs of the elderly population and to develop policies aimed at promoting healthy aging in CEE countries.

Discrepancies between the Spatial Distribution of Cancer Incidence and Mortality as an Indicator of Unmet Needs in Cancer Prevention and/or Treatment in Hungary.

There is a rich body of literature on the distribution of cancer incidence and mortality in socioeconomically different world regions, but none of the studies has compared the spatial distribution of mortality and incidence to see if they are consistent with each other. All malignant neoplasms combined and cervical, colorectal, breast, pancreatic, lung, and oral cancers separately were studied in the Hungarian population aged 25-64 years for 2007-2018 at the municipality level by sex. In each case, the spatial distribution of incidence and mortality were compared with each other and with the level of deprivation using disease mapping, spatial regression, risk analysis, and spatial scan statistics. A positive association between deprivation and mortality was found for each type of cancer, but there was no significant association for male colorectal cancer (relative risk (RR) 1.00; 95% credible interval (CI) 0.99-1.02), pancreatic cancer (RR: 1.01; 95%CI 0.98-1.04), and female colorectal cancer incidence (RR: 1.01; 95%CI 0.99-1.03), whereas a negative association for breast cancer (RR: 0.98; 95%CI 0.96-0.99) was found. Disease mapping analyses showed only partial overlap between areas of high incidence and mortality, often independent of deprivation. Our results highlight not only the diverse relationship between cancer burden and deprivation, but also the inconsistent relationship between cancer incidence and mortality, pointing to areas with populations that require special public health attention.

Mortality amenable to health care and its relation to socio-economic status in Hungary, 2004-08.

BACKGROUND: Recently, research focus has returned to amenable mortality to health care, despite the decreasing trend, as it remains a significant contributor to social and economic loss due to premature death. This article assesses the trends of amenable mortality over time and, its spatial inequalities with respect to deprivation, in Hungary. METHODS: An ecological analysis of mortality amenable to health care was carried out using smoothed indirectly standardized mortality ratios, calculated by full hierarchical Bayesian methods, at municipality level. The association between the spatial distribution of amenable mortality and deprivation was also assessed using a Hungarian specific deprivation index. RESULTS: Trends of mortality amenable to health care were characterized by a decreasing pattern across the studied period, 1996-2008. Areas of significantly high risk of amenable mortality were identified in the North-eastern, Eastern and South-western parts of Hungary. A statistically significant association was found between amenable mortality and deprivation status in both genders. After correcting for bias due to socio-economic confounders, the patterns of areas with excess risks significantly changed. CONCLUSION: Differences in deprivation alone cannot explain the spatial distribution of mortality amenable to health care. This study highlights the importance of exploring other factors (e.g. health-care system and individual life style) beyond socio-economic status, which affect health inequalities particularly for health policy makers, who are responsible for the mitigation of health disparities.

Characteristics of the Third COVID-19 Pandemic Wave with Special Focus on Socioeconomic Inequalities in Morbidity, Mortality and the Uptake of COVID-19 Vaccination in Hungary.

Governments are increasingly looking to vaccination to provide a path out of the COVID-19 pandemic. Hungary offers an example to investigate whether social inequalities compromise what a successful vaccine program can achieve. COVID-19 morbidity, mortality, and vaccination coverage were characterized by calculation of indirectly standardized ratios in the Hungarian population during the third pandemic wave at the level of municipalities, classified into deprivation quintiles. Then, their association with socioeconomic deprivation was assessed using ecological regression. Compared to the national average, people living in the most deprived municipalities had a 15-24% lower relative incidence of confirmed COVID-19 cases, but a 17-37% higher relative mortality and a 38% lower vaccination coverage. At an ecological level, COVID-19 mortality showed a strong positive association with deprivation and an inverse association with vaccination coverage (RRVaccination = 0.86 (0.75-0.98)), but the latter became non-significant after adjustment for deprivation (RRVaccination = 0.95 (0.84-1.09), RRDeprivation = 1.10 (1.07-1.14)). Even what is widely viewed as one of the more successful vaccine roll outs was unable to close the gap in COVID-19 mortality during the third pandemic wave in Hungary. This is likely to be due to the challenges of reaching those living in the most deprived municipalities who experienced the highest mortality rates during the third wave.

Unequal burden of COVID-19 in Hungary: a geographical and socioeconomic analysis of the second wave of the pandemic.

INTRODUCTION: We describe COVID-19 morbidity, mortality, case fatality and excess death in a country-wide study of municipalities in Hungary, exploring the association with socioeconomic status. METHODS: The spatial distribution of morbidity, mortality and case fatality was mapped using hierarchical Bayesian smoothed indirectly standardised ratios. Indirectly standardised ratios were used to evaluate the association between deprivation and the outcome measures. We looked separately at morbidity and mortality in the 10 districts with the highest and 10 districts with the lowest share of Roma population. RESULTS: Compared with the national average, the relative incidence of cases was 30%-36% lower in the most deprived quintile but the relative mortality and case fatality were 27%-32% higher. Expressed as incidence ratios relative to the national average, the most deprived municipalities had a relative incidence ratio of 0.64 (CI: 0.62 to 0.65) and 0.70 (CI: 0.69 to 0.72) for males and females, respectively. The corresponding figures for mortality were 1.32 (CI: 1.20 to 1.44) for males and 1.27 (CI: 1.16 to 1.39) for females and for case fatality 1.27 (CI: 1.16 to 1.39) and 1.32 (CI: 1.20 to 1.44) for males and females, respectively. The excess death rate (per 100 000) increased with deprivation levels (least deprived: 114.12 (CI: 108.60 to 119.84) and most deprived: 158.07 (CI: 149.30 to 167.23)). The 10 districts where Roma formed the greatest share of the population had an excess mortality rate 17.46% higher than the average for the most deprived quintile. CONCLUSIONS: Those living in more deprived municipalities had a lower risk of being identified as a confirmed COVID-19 case but had a higher risk of death. An inverse association between trends in morbidity and mortality by socioeconomic conditions should be a cause for concern and points to the need for responses, including those involving vaccination, to pay particular attention to inequalities and their causes.

Preventive Metformin Monotherapy Medication Prescription, Redemption and Socioeconomic Status in Hungary in 2018-2019: A Cross-Sectional Study.

This study was designed to characterize the spatial distribution of metformin medication used as first-line monotherapy for prevention of T2DM in relationship with the socioeconomic status (level of deprivation) and T2DM mortality at district level in a nationwide cross-sectional ecological study for the first time in a European country, Hungary. Risk analysis was used to estimate the relationships between socioeconomic status, characterized by tertiles of deprivation index, and mortality caused by diabetes, and metformin medication (both prescription and redemption) for the years of 2018 and 2019 at the district level. The spatial distribution of districts with a higher relative frequency of metformin prescriptions and redemptions showed a positive correlation with socio-economic deprivation. Significant association between the relatively high T2DM mortality and the highest level of deprivation could also be detected, but less-deprived regions with high T2DM mortality and low metformin utilization could also be identified. Although the statistical associations detected in this ecological study do not indicate a causal relationship, it is reasonable to suppose that the underuse of metformin medication may contribute to the unfavourable T2DM mortality in certain regions. Our findings underline the need for more effective preventive services including metformin medication to decrease T2DM morbidity and mortality burden.

Investigating the Geographic Disparities of Amenable Mortality and Related Ambulance Services in Hungary.

The aim of this study was to investigate how amenable mortality and related ambulance services differ on a county level in Hungary. The differences in mortality rates and ambulance services could identify counties where stronger ambulance services are needed. The datasets for 2018 consisted of county level aggregated data of citizens between the ages 15-64. The study examined how both the mortality rates and the ambulance rescue deliveries differ from the national average. The analyses were narrowed down to disease groups, such as acute myocardial infarction, hemorrhagic and ischemic stroke. Inequalities were identified regarding the distribution of number of ambulance deliveries, several counties had rates more than double that of the national average. For both mortality and ambulance services some of the counties had significantly better results and others had significantly worse compared to the national average. In Borsod-Abaúj-Zemplén county's case, hemorrhagic stroke mortality was significantly higher (1.73 [1.35-2.11]), while ambulance deliveries were significantly lower (0.58 [0.40-0.76]) compared to the national average. The research has shown that regarding the investigated mortality rates and ambulance services there are considerable differences between the counties in Hungary. In this regard policy makers should implement policies to tackle these discrepancies.

Antithrombotic Preventive Medication Prescription Redemption and Socioeconomic Status in Hungary in 2016: A Cross-Sectional Study.

This work was designed to investigate antithrombotic drug utilization and its link with the socioeconomic characteristics of specific population groups in Hungary by a comparative analysis of data for prescriptions by general practitioners and the redeemed prescriptions for antithrombotic drugs. Risk analysis capabilities were applied to estimate the relationships between socioeconomic status, which was characterized by quintiles of a multidimensional composite indicator (deprivation index), and mortality due to thromboembolic diseases as well as antithrombotic medications for the year 2016 at the district level in Hungary. According to our findings, although deprivation is a significant determinant of mortality due to thromboembolic diseases, clusters can be identified that represent exemptions to this rule: an eastern part of Hungary, consisting of two highly deprived counties, had significantly lower mortality than the country average; by contrast, the least-deprived northwestern part of the country, consisting of five counties, had significantly higher mortality than the country average. The fact that low socioeconomic status in general and poor adherence to antithrombotic drugs irrespective of socioeconomic status were associated with increased mortality indicates the importance of more efficient control of preventive medication and access to healthcare in all districts of the country to reduce mortality due to thromboembolic diseases.

Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios.

COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.

Late mortality in survivors of childhood cancer in Hungary.

The Hungarian Pediatric Oncology Network provides centralized treatment and population-based registration for cases of childhood cancer since 1973. We collected and analized data on late mortality, secondary malignancies and cardiac diseases in survivors (> 5 years) of childhood cancer to evaluate long-term risks. We extracted all solid tumour cases (3,650 followed up for 5-39.3 years, diagnosis: 1973-2008) from the database of the Hungarian Childhood Cancer Registry and checked against the Population Registry. Among the 301 patients who died after 5 years (8.2%) the most common causes of death were progression of primary cancer (52.5%), secondary malignancies (16%) and cardiovascular diseases (8%). Late mortality rates (SMR, total: 35,006 pyrs) showed highly elevated risk of death (SMR: 10.7 95% CI 9-12.4) for the second 5 years of follow up and moderately elevated risk for 10-year survivors (SMR: 3.5 95% CI 3-4.1). Marked differences were detected in the pattern of causes of death between diagnostic groups of primary cancer; with highest risks beyond 10 years for CNS tumours, Hodgkin disease, osteosarcoma and advanced stage neuroblastoma. The longstanding mortality risk for 5-year survivors underlines the need for tailored long-term follow-up and monitoring of late consequences according to the context of different primary diseases of childhood cancer.

Workforce crisis in primary healthcare worldwide: Hungarian example in a longitudinal follow-up study.

OBJECTIVE: The study was designed to explore the development of the general practitioner (GP) shortage in primary care and its characteristics in Hungary. DESIGN: Longitudinal follow-up study over the decade 2007-2016. METHODS: Analyses were performed on changes in number, age and sex of GPs by practice type (adult, paediatric and mixed), as well as on their geographical distribution and migration between areas characterised by deprivation index (DI) at municipality level. The association between deprivation and vacancy for GPs was studied by risk analysis. The number of population underserved was defined by DI quintile. SETTING AND SUBJECTS: The study involved all general practices and GPs in the period examined. MAIN OUTCOME MEASURE: It is showed that the number of general practices with unfilled GP posts was increasing exponentially, mainly in the most deprived areas of the country. RESULTS: A decrease in the number of GPs in all types of practices, especially in mixed (by 7.7%; p<0.001) and paediatric (by 6.5%; p<0.001) ones, was shown; the number of adult practices with unfilled GP posts doubled, while the number of paediatric practices with a vacancy for a paediatrician more than tripled. The average age of GPs was increased by 3.7 years (p<0.001) in adult, by 5.4 years (p<0.001) in paediatric and by 4.2 years (p<0.001) in mixed practices. In 2007, 52.27% (95% CI 51.03 to 53.5) of the GPs were women, and this rate increased to 56.19% (95% CI 54.93 to 57.44) by the end of the decade. An exponential association between relative vacancy rate and deprivation was confirmed. As a result of the migration of GPs, in the most deprived areas, the number of GPs decreased by 8.43% (95% CI 5.86 to 10.99). CONCLUSIONS: The workforce crisis in Hungarian primary care is progressively deepening and resulting in more severe inequity in access to healthcare.

c-Myb regulates tumorigenic potential of embryonal rhabdomyosarcoma cells.

Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors, the most common sub-types are embryonal (eRMS) and alveolar (aRMS) rhabdomyosarcoma. Immunohistochemical analysis revealed c-Myb expression in both eRMS and aRMS. c-Myb has been reported to be often associated with malignant human cancers. We therefore investigated the c-Myb role in RMS using cellular models of RMS. Specific suppression of c-Myb by a lentiviral vector expressing doxycycline (Dox)-inducible c-Myb shRNA inhibited proliferation, colony formation, and migration of the eRMS cell line (RD), but not of the aRMS cell line (RH30). Upon c-Myb knockdown in eRMS cells, cells accumulated in G0/G1 phase, the invasive behaviour of cells was repressed, and elevated levels of myosin heavy chain, marker of muscle differentiation, was detected. Next, we used an RD-based xenograft model to investigate the role of c-Myb in eRMS tumorigenesis in vivo. We found that Dox administration did not result in efficient suppression of c-Myb in growing tumors. However, when c-Myb-deficient RD cells were implanted into SCID mice, we observed inefficient tumor grafting and attenuation of tumor growth during the initial stages of tumor expansion. The presented study suggests that c-Myb could be a therapeutic target in embryonal rhabdomyosarcoma assuming that its expression is ablated.

Percepción e impacto en la confianza de los residentes de cirugía general de un curso de anastomosis intestinal abierta en un ambiente simulado

Objetivo: Evaluar el impacto de un curso de anastomosis intestinal abierta simulada en residentes de cirugía general. Materiales y Métodos: Estudio prospectivo no aleatorizado. Se aplicó un curso para residentes del programa de cirugía general del Hospital Clínico Universidad de Chile en 2021 en su primera versión y una segunda vez en 2022. Se evaluó la percepción y confianza con encuestas pre y post curso. Resultados: Participaron diecisiete residentes. De ellos, 16 residentes habían asistido previamente en la técnica básica, 10 nunca habían realizado una anastomosis intestinal a un paciente real como primer cirujano, en su mayoría residentes de segundo y tercer año. El nivel de confianza promedio para realizar una anastomosis intestinal en pacientes previo al curso fue de 1,86/7, 3/7 y 5,38/7 para el primer, segundo y tercer año, respectivamente. De manera global, previo al curso, los residentes promediaron una confianza de 3,09/7. Después del curso, 15/16 residentes estuvieron de acuerdo o muy de acuerdo en que mejoró la confianza en la técnica; que el modelo representa correctamente la situación real, y que los modelos simulados son más efectivos para el aprendizaje que la experiencia clínica por sí sola. Los residentes aumentaron su confianza en 2,47 puntos, alcanzando un promedio de 5,56/7 para la técnica (p = 0,001). Conclusiones: El curso de anastomosis intestinal abierta es percibido por los residentes como efectivo, realista y aumenta, significativamente, la confianza en la realización de esta técnica.

Objective: To evaluate the impact of a simulated open intestinal anastomosis course on general surgery residents. Materials and Methods: Prospective non-randomized study. A course was applied to residents in the general surgery program at the Clinical Hospital of the University of Chile in 2021 for its first version and a second time in 2022. Perception and confidence were evaluated with pre-and post-course surveys. Results: Seventeen residents participated. Of these, 16 residents had previously attended the basic technique, 10 had never performed an intestinal anastomosis as a first surgeon on a real patient, mostly second and third-year residents. The average confidence level for performing an intestinal anastomosis on patients prior to the course was 1.86/7, 3/7, and 5.38/7 for the first, second, and third year, respectively. Overall, prior to the course, residents averaged a confidence of 3.09/7. After the course, 15/16 residents agreed or strongly agreed that it improved their confidence in the technique; that the model accurately represents the real situation, and that simulated models are more effective for learning than clinical experience alone. Residents increased their confidence by 2.47 points, reaching an average of 5.56/7 for the technique (p = 0.001). Conclusions: The open intestinal anastomosis course is perceived by residents as effective, realistic, and significantly increases confidence in performing this technique.

Resultados a largo plazo del tratamiento quirúrgico de Hernias Hiatales tipo III y IV con y sin refuerzo protésico

Introducción: El tratamiento de las Hernias Hiatales (HH) tipo III y IV es quirúrgico. Hay controversia sobre el refuerzo con malla. Nuestro objetivo fue comparar los resultados a largo plazo entre el uso o no de refuerzos protésicos. Materiales y Métodos: Cohorte prospectiva de 95 pacientes con HH tipo III y IV, entre los años 1997 y 2015 en el Hospital Clínico de la Universidad de Chile. Se evaluaron las características radiológicas, endoscópicas y funcionales pre y postoperatorias. Recidiva definida como recurrencia mayor a 3 cm. Análisis estadístico con chi2 y Test U-Mam-Whitney. P-value a 10 años) de HH tipo III y IV reparadas quirúrgicamente, no hay diferencias en la recidiva clínica con o sin el uso de mallas.

Introduction: The treatment of Hiatal Hernias (HH) type III and IV is surgical. There is controversy about reinforcement with mesh. Our objective was to compare the long-term results between the use or not of prosthetic reinforcements. Materials and Methods: Prospective cohort of 95 patients with HH type III and IV, between 1997 and 2015 at the Clinical Hospital of the University of Chile. Pre and postoperative radiological, endoscopic and functional characteristics were evaluated. Recurrence defined as a recurrence greater than 3 cm. Statistical analysis with chi2 and U-Mann-Whitney test. p-value 10 years) of surgically repaired type III and IV HH, there are no differences in clinical recurrence with or without the use of mesh.

Reference genes for quantitative real time PCR in UVB irradiated keratinocytes.

Real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a sensitive and highly reproducible method often used for determining mRNA levels. To enable proper comparison of gene expression genes expressed at stabile levels within the cells in the studied experimental system need to be identified and used as reference. Ultraviolet B (UVB) radiation is an exogenous carcinogenic stimulus in keratinocytes, and UVB elicited changes have extensively been studied by qRT-PCR, yet a comparison of commonly used reference genes in UVB treatment is lacking. To find the best genes for compensating slight inter-sample variations in keratinocytes in UVB experiments and to understand the potential effects of improper reference gene (RG) selection we have analyzed the mRNA expression of 10 housekeeping genes in neonatal human epidermal keratinocytes (NHEK) after UVB treatment. The biological effect of the used UVB light source was validated by trypane blue exclusion, MTT and comet assays. 20-40mJ/cm(2) dose was chosen for the experiments. The stability of the 10 RGs was assessed by the GeNorm and Normfinder software tools. Regardless of their slightly different algorithm the programs found succinate dehydrogenase complex subunit A (SDHA) to be the best individual RG and SDHA and phosphoglycerate kinase-1 (PGK1) as the most suitable combination. Analysis of the expression of tumor necrosis factor alpha (TNFalpha) and vascular endothelial growth factor (VEGF) found that while the perception of changes in TNF-alpha, a gene undergoing marked upregulation after UVB irradiation is independent of the used RG, changes seen in the more modestly upregulated VEGF are greatly effected by reference gene selection. These findings highlight the importance of reference gene selection in UVB irradiation experiments, and provide evidence that using SDHA or the combination of SDHA and PGK1 as standards could be a reliable method for normalizing qRT-PCR results in keratinocytes after UVB treatment.