Educational pathways of childhood cancer survivors-a parental cohort.

PURPOSE: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients. METHODS: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings. RESULTS: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii). CONCLUSIONS: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed. IMPLICATIONS FOR CANCER SURVIVORS: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.

Toxicity and larvicidal activity on Aedes aegypti of citronella essential oil submitted to enzymatic esterification / Toxicidade e atividade larvicida sobre Aedes aegypti de óleo essencial de citronella submetido à esterificação enzimática

Abstract The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-1 were obtained for the essential oil and 4.36 μg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-1 for the essential oil of citronella and 86.30 μg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.

Resumo O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 μg mL-1 para o óleo essencial e 4,36 μg mL-1 para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 μg mL-1 para o óleo essencial de citronela e 86,30 μg mL-1 para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.

Toxicity and larvicidal activity on Aedes aegypti of citronella essential oil submitted to enzymatic esterification / Toxicidade e atividade larvicida sobre Aedes aegypti de óleo essencial de citronella submetido à esterificação enzimática

The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 μg mL-¹ were obtained for the essential oil and 4.36 μg mL-¹ for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 μg mL-¹ for the essential oil of citronella and 86.30 μg mL-¹ for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.

O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 μg mL-¹ para o óleo essencial e 4,36 μg mL-¹ para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 μg mL-¹ para o óleo essencial de citronela e 86,30 μg mL-¹ para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.

Toxicity and larvicidal activity on Aedes aegypti of citronella essential oil submitted to enzymatic esterification

Abstract The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 g mL-1 were obtained for the essential oil and 4.36 g mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 g mL-1 for the essential oil of citronella and 86.30 g mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.

Resumo O óleo essencial de citronela (Cymbopogon winterianus) possui diversas atividades biológicas, entre elas a ação repelente a insetos. Alguns estudos mostraram que os ésteres do ácido cinâmico podem ser aplicados como pesticidas naturais, inseticidas e fungicidas. Nesse contexto, o objetivo do presente trabalho foi avaliar a produção de ésteres a partir do óleo essencial de citronela com ácido cinâmico via esterificação enzimática. Além disso, foi investigada a toxicidade do óleo essencial antes e após a esterificação contra Artemia salina e a ação larvicida sobre Aedes aegypti. Os ésteres foram produzidos utilizando ácido cinâmico como agente acilante e óleo essencial de citronela (3: 1) em heptano e 15% em peso da enzima NS 88011 como biocatalisadores, a 70 ° C e 150 rpm. As taxas de conversão de cinamatos de citronelil e geranil foram 58,7 e 69,0% para NS 88011, respectivamente. Para a toxicidade sobre Artemia salina foram obtidos CL50 de 5,29 g mL-1 para o óleo essencial e 4,36 g mL-1 para os óleos esterificados com NS 88011. Na atividade inseticida contra larvas de Aedes aegypti, obteve-se CL50 de 111,84 g mL-1 para o óleo essencial de citronela e 86,30 g mL-1 para os óleos esterificados com a enzima NS 88011, indicando alta toxicidade dos ésteres. Os resultados demonstraram que as amostras avaliadas apresentam potencial de aplicação como bioinseticida.

Melanoma nodular amelanótico: a propósito de un caso / Amelanotic nodular melanoma: a case report

RESUMEN Introducción: El melanoma es un tumor maligno de estirpe melanocítica que constituye el sexto cáncer más frecuente en la población general y tiene una alta capacidad para producir metástasis. Aproximadamente el 95% de los melanomas primarios pertenecen a cuatro tipos clínico-patológicos: extensivo superficial, nodular, lentigo maligno y lentiginoso acral. El 5% restante corresponde a variantes menos frecuentes entre las que se encuentra el melanoma amelanótico, que representa entre el 0.4-27.5% de los casos de este subgrupo. Objetivo: Presentar un caso de un melanoma amelanótico, como una variante que puede acompañar a cualquier otro tipo clínico de melanoma, en este caso a uno de tipo nodular,lesión que, debido a su disminución o ausencia de pigmento, puede conducir a errores diagnósticos que inciden en la demora en el tratamiento y reducen la sobrevida de los pacientes que lo padecen. Caso Clínico: Se presenta el caso de un paciente de sexo masculino de 75 años que acude por presentar una lesión tumoral exofítica en la frente, de aproximadamente un año de evolución. Al examen físico se observa la lesión tumoral cupuliforme, eritematosa y brillante, que bajo dermatoscopio de luz polarizada muestra un patrón vascular polimorfo a predominio de vasos lineales gruesos. Se plantean varios diagnósticos diferenciales entre los que se destacan: carcinoma basocelular, granuloma piógeno, linfoma y metástasis cutáneas; se realiza una toma de muestra para biopsia y técnicas de tinción con inmunohistoquímica, que confirman el diagnóstico de melanoma, se decide exéresis de la tumoración con márgenes y seguimiento multidisciplinario del caso. Conclusiones: Las variantes hipo/amelanóticas del melanoma son poco frecuentes y su diagnóstico presenta dificultades que suelen generar demoras que influyen en el tratamiento y pronóstico de la enfermedad. La dermatoscopía se presenta como una herramienta sumamente útil que puede aumentar la sospecha diagnóstica de estos tumores, aunque el estudio histopatológico continúa siendo el patrón de referencia para el diagnóstico, así como para el abordaje terapéutico y seguimiento ulteriores.

ABSTRACT Introduction: Melanoma is a malignant melanocytic tumor that constitutes the sixth most frequent cancer in the general population and has a high capacity to produce metastasis. Approximately 95% of primary melanomas belong to four clinicopathological types: extensive superficial, nodular, lentigo maligna, and acral lentiginous. The remaining 5% correspond to less frequent variants, among which is amelanotic melanoma, that represents between 0.4-27.5% of the cases in this subgroup. Objective: To present a case of an amelanotic melanoma, as a variant that can accompany any other clinical type of melanoma, in this case a nodular type, a lesion that, due to its decrease or absence of pigment, can lead to diagnostic errors that affect the delay in treatment and reduce the survival of patients who suffer from it. Clinical Case: The case of a 75-year-old male patient who presents with an exophytic tumor lesion on the forehead of approximately one year of evolution. Physical examination reveals a bright, erythematous, dome-shaped tumor which shows a polymorphous vascular pattern with a predominance of thick linear vessels under a polarized light dermatoscope. Several differential diagnoses are proposed, among which the following stand out: basal cell carcinoma, pyogenic granuloma, lymphoma, and skin metastases; a sample is taken for biopsy and staining techniques with immunohistochemistry, which confirm the diagnosis of melanoma, it is decided to excise the tumor with margins and multidisciplinary follow-up of the case. Conclusions: The hypo / amelanotic variants of melanoma are rare and their diagnosis presents difficulties that usually generate delays that influence the treatment and prognosis of the disease. Dermoscopy is presented as an extremely useful tool that can increase the diagnostic suspicion of these tumors, although the histopathological study continues being the gold standard for diagnosis, as well as for the therapeutic approach and subsequent follow-up.

Prevalence and differences of ideal cardiovascular health in urban and rural adolescents in the Region of Tyrol: results from the EVA Tyrol study.

PURPOSE: Early adoption of a healthy lifestyle has positive effects on cardiovascular health (CVH) in adulthood. In this study, we aimed to assess CVH metrics in a cohort of healthy teenagers with focus on differences between rural and urban areas. METHODS: The Early Vascular Aging (EVA) Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Data from the baseline and control group (prior to health intervention) are included in the current analysis. CVH determinants (smoking, body mass index, physical activity, dietary patterns, systolic and diastolic blood pressure, total cholesterol and fasting blood glucose) were assessed and analyzed for urban and rural subgroups separately by univariate testing. Significant variables were added in a generalized linear model adjusted for living in urban or rural area with age and sex as covariates. Ideal CVH is defined according to the guidelines of the American Heart Association. RESULTS: 2031 healthy adolescents were enrolled in the present study (56.2% female, mean age 16.5 years). 792 adolescents (39.0%) were from urban and 1239 (61.0%) from rural areas. In 1.3% of adolescents living in urban vs. 1.7% living in rural areas all CVH determinants were in an ideal range. Compared to the rural group, urban adolescents reported significantly longer periods of moderate to vigorous-intensive activity (median 50.0 min/day (interquartile range 30-80) vs. median 40.0 min/day (interquartile range 25-60), p < 0.01). This observation remained significant in a generalized linear model (p < 0.01). There were no significant differences between the study groups regarding all other CVH metrics. CONCLUSION: The low prevalence of ideal CVH for adolescents living in urban as well as rural areas highlights the need for early health intervention. Geographic differences must be taken into account when defining targeted subgroups for health intervention programs.

Toxicity and larvicidal activity on Aedes aegypti of citronella essential oil submitted to enzymatic esterification.

The essential oil of citronella (Cymbopogon winterianus) has several biological activities, among them the insect repellent action. Some studies showed that cinnamic acid esters can be applied as natural pesticides, insecticides and fungicides. In this context, the objective of the present work was to evaluate the production of esters from citronella essential oil with cinnamic acid via enzymatic esterification. Besides, the essential oil toxicity before and after esterification against Artemia salina and larvicidal action on Aedes aegypti was investigated. Esters were produced using cinnamic acid as the acylating agent and citronella essential oil (3:1) in heptane and 15 wt% NS 88011 enzyme as biocatalysts, at 70 °C and 150 rpm. Conversion rates of citronellyl and geranyl cinnamates were 58.7 and 69.0% for NS 88011, respectively. For the toxicity to Artemia salina LC50 results of 5.29 µg mL-1 were obtained for the essential oil and 4.36 µg mL-1 for the esterified oils obtained with NS 88011. In the insecticidal activity against Aedes aegypti larvae, was obtained LC50 of 111.84 µg mL-1 for the essential oil of citronella and 86.30 µg mL-1 for the esterified oils obtained with the enzyme NS 88011, indicating high toxicity of the esters. The results demonstrated that the evaluated samples present potential of application as bioinsecticide.

Health-Related Behaviour Among Children of Childhood Cancer Survivors in Germany.

Purpose: Childhood cancer survivors fear that previous therapy could not only impair their own but also their children's health. We examined whether health-related behaviour in children of childhood cancer survivors differs from the general population. Methods: Our first nationwide survey wave (2013-2014) surveyed offspring health in 396 German childhood cancer survivors known to have a child of their own. Answers about health behaviour were analysed using descriptive statistics. Data were collected for 418 offspring and 394 could be integrated for matched-pair analyses with data from the German general population (KIGGS, n=17 641). Results: Teeth-cleaning routine, body-mass-index or subjective body image evaluation by parents were no different from children in the general population. Parents who included a cancer survivor smoked less in the presence of their children (p=0.01). During pregnancy, mothers in cancer survivor parent pairs abstained from drinking alcohol more often (p=0.01) and smoked less (p=0.05). While the calculated effect sizes (Phi) were generally low (0.135-0.247), children from cancer survivors played less outdoors than peers did (p=0.01). Boys participated in sports outside a club more often (p=0.05) and watched less TV on weekdays (p=0.01) and girls spent more time on the computer during weekdays than peers did (p=0.01). Conclusions: This study provides the first data for health-related behaviour in cancer survivors' offspring and sheds light on differences to parenting in the general population. Multivariate analyses in a larger study population are needed to relate these differences to fear issues in cancer survivors.

Treadmill measures of ambulation rates in ovine models of spinal cord injury and neuropathic pain.

Our laboratories are developing treadmill-based gait analysis employing sheep to investigate potential efficacy of intra-dural spinal cord stimulation in the treatment of spinal cord injury and neuropathic pain. As part of efforts to establish the performance characteristics of the experimental arrangement, this study measured the treadmill speed via a tachometer, video belt-marker timing and ambulation-rate observations of the sheep. The data reveal a 0.1-0.3% residual drift in the baseline (unloaded) treadmill speed which increases with loading, but all three approaches agree on final speed to within 1.7%, at belt speeds of ≈ 4 km/h. Using the tachometer as the standard, the estimated upper limit on uncertainty in the video belt-marker approach is ± 0.18 km h(-1) and the measured uncertainty is ± 0.15 km h(-1). Employment of the latter method in determining timing differences between contralateral hoof strikes by the sheep suggests its utility in assessing severity of SCI and responses to therapeutic interventions.

Nationwide Survey on the Health of Offspring from Former Childhood Cancer Patients in Germany.

BACKGROUND: Increased risk for infertility from cancer treatment and fear of health impairment in their offspring may prevent survivors of childhood cancer from having own children. Even though most studies report no increased risk for malformations, in our German fertility study 2008 a higher occurrence of cleft lip and palate was found in offspring of former patients. METHODS: Since 2010 we assess offspring's health in a survey-based multicenter study, comparing diseases, well-being, healthcare utilization and health-related behavior between offspring from survivors, siblings or the general population. Within a first nationwide survey wave survivors who were known to have at least one child by previous fertility studies, received a questionnaire supported by the German Childhood Cancer Registry. Questionnaires were based on the KiGGS study on children's health in the German general population conducted by the Robert-Koch Institute (n=17,641). RESULTS: Questionnaires on 418 children were answered by 65% (254/393) of survivors contacted to participate in the first nationwide offspring study wave. Participants were more likely to be female (p<0.01), to have achieved higher educational levels (p<0.05) and to be a survivor of a soft tissue tumor (p<0.05). Former patients expressed moderate to high anxiety for the occurrence of cancer in 74% and feared other diseases in their children in 20%. CONCLUSION: Offspring health is a topic of major relevance to former patients. Our offspring study is currently being extended to ~1500 offspring of childhood cancer survivors in Europe.

Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study.

PURPOSE: Fertility impairment and recovery after haematopoietic stem cell transplantation (HSCT) have been reported in both sexes, but little is known about how they develop over time. Our aim was to describe the dynamics of fertility impairment and recovery after HSCT. METHODS: We retrieved treatment and fertility data for up to 12 years of 361 paediatric patients with malignant and non-malignant diseases from seven European centres. The patients had been treated with allogeneic HSCT between 2000 and 2005. RESULTS: Development of fertility impairment was observed in males (123/217, 56%) after a median time of 2.6 years (range 0.1-11.4) and in females (82/144, 57%) after 2.3 years (range 0.1-12.0) after HSCT. Different busulfan dosages had only a slight impact on the onset of fertility impairment (busulfan ≥ 16 mg/kg with a median time to fertility impairment of 2.9 vs. 3.9 years after busulfan <14 mg/kg). Recovery from fertility impairment was observed in 17 participants after a median time of 4.1 years (range 1-10.6) in females (10/144, 7%) and 2.0 years (range 1-6.3) in males (7/217, 3 %) after fertility impairment first appeared. CONCLUSIONS: In the light of the dynamics of fertility impairment and recovery in the HSCT patients reviewed, these patients should be counselled comprehensively regarding fertility preservation measures.

Dynamics of fertility impairment in childhood brain tumour survivors.

PURPOSE: Fertility impairment and recovery after chemo- and radiotherapy have been reported in both male and female childhood cancer survivors, but little is known about the dynamics. Our aim, therefore, was to describe the development of fertility impairment and possible recovery in childhood brain tumour survivors. METHODS: In this longitudinal study, we included 144 survivors, who were treated in two German paediatric oncology centres between 2000 and 2005. Fertility parameters were retrieved from medical records up to 12 years after diagnosis. RESULTS: Participants with age ≥13 years and formerly cranial irradiation ≥30 Gray (n = 23), including 83 % (n = 19) with craniospinal irradiation ≥30 Gray, had a higher median FSH concentration compared to 29 patients without chemoradiotherapy: 8.3 IU/l (IQR 6.5-11.2) versus 4.1 IU/l (IQR 3.2-5.1) 2 years after initial treatment; 8.9 IU/l (IQR 8.5-10.8) versus 4.2 IU/l (IQR 2.4-6.7) after 8 years; and 7.1 IU/l (IQR 6.7-7.7) versus 3.5 IU/l (IQR 2.8-4.2) after 10 years. Altogether, 11/65 women reported the occurrence of amenorrhoea 6.0 years (range 1-10) after diagnosis. Five of these women later developed a regular menstrual cycle without hormone replacement therapy. Patients' chance of recovery from fertility impairment was increased with time since diagnosis (p = 0.074). CONCLUSION: Signs of fertility impairment such as amenorrhoea and elevated FSH levels were observed at variable time points between 1 and 12 years after chemoradiotherapy. Decreasing FSH levels were observed 1-7 years after elevation and were interpreted either as an atrophy of the pituitary gland or as recovery from fertility impairment.

Human endothelial lecitin-like oxLDL receptor-1 (LOX-1) expression is not associated with impairment of endothelium-dependent vasoreactivity in conduit vessels.

UNLABELLED: The cellular uptake of oxidized low density lipoprotein (LDL) is mediated through the oxidized LDL receptor-1, LOX-1. We investigated whether circulating factors link LOX-1 expression in endothelial cells and impaired endothelium-dependent vasoreactivity (EDVR) as functional indicator of atherogenesis. EDVR was measured as flow-mediated dilation (FMD) of the brachial artery in 27 patients with a known history of cardiovascular disease. Human umbilical vein endothelial cells (HUVEC) were incubated with bradykinin or prostacyclin in the presence of tumour necrosis factor-alpha (TNF-α) or with serum of each patient for four hours. Total mRNA and protein extracts were analysed for LOX-1 and eNOS expression relative to the expression in medium-treated cells and corrected for GAPDH expression. RESULTS: Prostacyclin and bradykinin did not modulate LOX-1 basal expression but were able to prevent significantly the up-regulation of LOX-1 expression by TNF-α, in HUVEC in vitro. Impaired EDVR was associated significantly with reduced endothelial nitric oxide synthase (eNOS) protein expression in HUVEC (r=0.788, P<0.001), diabetes (P=0.024), and smoking status (yes/no, P=0.047). In contrast, no such association was established with LOX-1 mRNA (r=0.292, P=0.138) or with LOX-1 protein expression in HUVEC (r=0.201, P=0.312). CONCLUSIONS: Using a combination of in vitro experiments with in vivo measurements, we found no evidence that endothelial LOX-1 expression and EDVR mediated through circulating factors were associated.

Impact of cranial irradiation and brain tumor location on fertility: a survey.

As survival rates of patients with childhood brain tumors have increased to 75%, treatment related side effects are of particular importance. The present study evaluated questionnaire-based fertility characteristics in cancer survivors treated with irradiation to the hypo-thalamic-pituitary-axis.A nationwide survey was conducted in collaboration with the German Childhood Cancer Registry. Questionnaire and treatment data could be retrieved for 1110 former childhood cancer patients with cranial irradiation and/or chemotherapy.Survivors receiving ≥30 gray vs. 18-29 gray and 0-17 gray to the pituitary gland reported less pregnancies or less with their partners (7.4% vs. 32.8% vs. 12.4%; p<0.001), were more often infertile (40% vs. 9.4% vs. 12.5%; p<0.001) and the female participants, had a higher frequency of permanent amenorrhea (16.7% vs. 1.7% vs. 0%; p<0.001).Irradiation of the pituitary gland ≥ 30 gray seemed to be associated with less pregnancies and increased permanent amenorrhea in women. Future studies need to be conducted to confirm these results. Increased knowledge of treatment related side effects might help brain tumor patients to improve their family planning if necessary by gonadotropine replacement.

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology.

PURPOSE: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. MATERIALS AND METHODS: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. RESULTS: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy × cm2, respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy × cm2) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy × cm2) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7%), and revealed a decreasing influence of the interventionalist's experience (-8.6% and -4.9% per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. CONCLUSION: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts.

Educational level of childhood brain tumor survivors: results from a German survey.

BACKGROUND: Among adult survivors of childhood brain tumors in Germany, we assessed their educational level and examined potentially influencing factors. PATIENTS AND METHODS: A questionnaire was sent to 505 childhood brain tumor survivors listed in the German Childhood Cancer Registry. 203/505 (40.2%) patients with treatment and educational data were included in the analysis.Of the included brain tumor survivors 54.7% (111/203) were male, the median age was 11.0 (1-15) years at diagnosis and 22.0 (19-37) years at the time of the survey. 34.8% (95%-CI 25.1-44.5) of female and 34.9% (26.0-43.8) of male survivors achieved a high school diploma. Survivors who had received irradiation had less likely obtained a high school diploma compared to those without irradiation. However, this association was statistically not significant: for either craniospinal or tumor irradiation adjusted odds ratio was 0.54 (0.08-3.76); for those with a combination of craniospinal and tumor irradiation 0.51 (0.07-3.59). Participants aged 6-10 years at diagnosis achieved a higher educational level 2.24 (0.45-11.25) compared to younger patients. CONCLUSION: A third of the childhood brain tumor survivors who participated in our survey obtained the highest school leaving certificate. This may be biased by an overrepresentation of well-educated survivors without major cancer-related late effects. The influence of the patients' strong motivation following a severe illness combined with the intensive psychosocial and/or pedagogical support on education needs to be examined in future studies.

Fertility after allogeneic haematopoietic stem cell transplantation in childhood and adolescence.

Infertility is a major late effect in patients receiving haematopoietic stem cell transplantation (HSCT). The aim of this study was to determine the proportion of patients having fertility impairment after allogeneic HSCT in childhood/adolescence and to identify the potential risk factors. Treatment and fertility data of paediatric patients with malignant and non-malignant diseases treated with allogeneic HSCT between 2000 and 2005 were collected from seven European centres. Data were obtained for 138 female and 206 male patients after a median follow-up of 6 years (range 3-12). The patients' median age was 13 years (range 4-28) at the time of HSCT and 19 (range 12-35) years at the time of the enquiry. Seven children were born to the overall group, all at term and healthy. Fertility impairment was suspected in 69% males and 83% females. Start of treatment at age 13 years was a risk factor in females (odds ratio (OR) 4.7; 95% confidence interval (CI), 1.5 to 14.9), whereas pre-pubertal therapy was a risk factor in males (OR 0.4; 95% CI, 0.2 to 0.8). The major treatment-related risk factors were BU in females (OR 47.4; 95% CI, 5.4 to 418.1) and TBI in males (OR 7.7; 95% CI, 2.3 to 25.4). In light of the significant proportion of HSCT patients reviewed with impaired fertility, fertility conservation procedures should be considered for all patients undergoing HSCT, particularly those receiving TBI or BU-based preparative regimens.

Cardioprotection of 17,18-epoxyeicostetraenoic acid in ischemia/reperfusion is mediated by cyclooxygenase-2: a study in a rat model.

BACKGROUND/PURPOSE: Arachidonic acid and related cardioprotective eicosanoids are released in myocardial ischemia/reperfusion injury. The present study analyzes the effects of the eicosapentaenoic acid derived 17,18-epoxyeicostetraenoic acid on isolated cardiomyocytes and investigates whether 17,18-epoxyeicostetraenoic acid serves as a potential factor in the cardio-depressant postischemic effluent. BASIC PROCEDURES: After 10 minutes of global ex vivo stop-flow ischemia, adult rat hearts were reperfused and coronary postischemic effluent was collected over a period of 30 seconds. Nonischemic effluent was collected prior to ischemia. The effects of 17,18-epoxyeicostetraenoic acid on calcium (Ca(2+)) metabolism and contraction frequency of isolated neonatal rat cardiomyocytes were tested and compared with the effects of prior collected postischemic and nonischemic effluents. Isolated neonatal cardiomyocytes were preincubated with selective (NS-398, SC-560) and nonselective cyclooxygenase inhibitors (indomethacin) to determine whether cardio-depressive effects are mediated by cyclooxygenase. FINDINGS: In contrast to the nonischemic effluent, both 17,18-epoxyeicostetraenoic acid and the postischemic effluent induced a comparable decrease of the Ca(2+) transient and the contraction frequency (P < .05 vs control). The cardio-depressive effects of 17,18-epoxyeicostetraenoic acid and the postischemic effluent were significantly attenuated after preincubation with the unselective cyclooxygenase inhibitor indomethacin and the selective cyclooxygenase-2 inhibitor NS-398 (P < .05 vs control). Selective cyclooxygenase-1 inhibition with SC-560 did not influence the effect of 17,18-epoxyeicostetraenoic acid and the postischemic effluent. CONCLUSIONS: Our data show that the cardio-depressive effects of 17,18-epoxyeicostetraenoic acid are comparable with the postischemic effluent and are mediated by cyclooxygenase-2. Our results suggest a potential cardioprotective role of the eicosanoid 17,18-epoxyeicostetraenoic acid in heart ischemia/reperfusion injury.

Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence.

BACKGROUND: Since prevalence of and reasons for infertility were unclear in survivors of childhood cancer we conducted a two centre survey in 2006 and nationwide in 2008. In 2008/2009 we undertook a study entitled "Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence". PATIENTS AND METHODS: Letters were sent to 748 former paediatric oncological patients who were at least 18 years of age at the time of the survey. Serum and sperm samples were analysed. RESULTS: We obtained 159 blood samples (86 women, 73 men). 42 men took part in the sperm analyses. The average participants' age at the time of the survey was 25 years. The anti-Mullerian hormone levels (AMH) in 14/86 female participants (16 %) were < 0.1 ng/ml. The follicular reserve of these women seemed manifestly impaired, which is consistent with suspected infertility. The AMH levels in 21/86 women (24 %) were 0.1 - 1.0 ng/ml indicating limited follicular reserve and therefore suspected early ovarian failure. Inhibin B levels of < 80 pg/ml and FSH levels of > 10 IU/L were found in 23/73 male participants (32 %), which may indicate impaired spermiogenesis with increased risk of infertility. 13/42 sperm analyses (31 %) revealed azoospermia. DISCUSSION: Paediatric oncological therapy seems to have led to fertility impairment in about 1/3 of the participants. Considering this serious impairment, patients and their families should be given comprehensive counselling ahead of therapy to enable fertility-preserving measures. For persons who wish to have children after undergoing therapy we recommend a hormone and sperm analysis. An early analysis may enable a more successful family planning.

Fcgamma-receptor IIa polymorphism and the role of immunoadsorption in cardiac dysfunction in patients with dilated cardiomyopathy.

In patients with dilated cardiomyopathy (DCM), cardiac autoantibodies are able to bind with their Fab fragment to epitopes on cardiomyocytes, but thereafter they crosslink through their Fc fragment to cardiac Fc(gamma)-receptor IIa. Polymorphic variability of the Fc(gamma)-receptor IIa is associated with modified affinity of immunoglobin G (IgG) binding and may influence therapeutic effects. In this study, 103 consecutive DCM patients were treated with immunoadsorption (IA) therapy with subsequent IgG substitution (IA/IgG). Echocardiography was performed at baseline and again at 3 and 6 months after IA/IgG. Fc(gamma)-receptor IIa polymorphism R/H131 was genotyped using a nested sequence-specific primer polymerase chain reaction (PCR). Patients with the Fc(gamma)-receptor IIa genotype R/R131 showed significantly greater improvement in left ventricular (LV) function than patients with the R/H131 or H/H131 genotypes did. Irrespective of the Fc(gamma)-receptor polymorphism, patients with shorter disease duration and a more impaired LV function responded with a greater increase in LV ejection fraction (LVEF). Therefore, the Fc(gamma)-receptor polymorphism influences the efficacy of immunomodulatory therapy involving IA/IgG.