Agricultural land use and human presence around breeding sites increase stress-hormone levels and decrease body mass in barn owl nestlings.

Human activities can have a suite of positive and negative effects on animals and thus can affect various life history parameters. Human presence and agricultural practice can be perceived as stressors to which animals react with the secretion of glucocorticoids. The acute short-term secretion of glucocorticoids is considered beneficial and helps an animal to redirect energy and behaviour to cope with a critical situation. However, a long-term increase of glucocorticoids can impair e.g. growth and immune functions. We investigated how nestling barn owls (Tyto alba) are affected by the surrounding landscape and by human activities around their nest sites. We studied these effects on two response levels: (a) the physiological level of the hypothalamus-pituitary-adrenal axis, represented by baseline concentrations of corticosterone and the concentration attained by a standardized stressor; (b) fitness parameters: growth of the nestlings and breeding performance. Nestlings growing up in intensively cultivated areas showed increased baseline corticosterone levels late in the season and had an increased corticosterone release after a stressful event, while their body mass was decreased. Nestlings experiencing frequent anthropogenic disturbance had elevated baseline corticosterone levels, an increased corticosterone stress response and a lower body mass. Finally, breeding performance was better in structurally more diverse landscapes. In conclusion, anthropogenic disturbance affects offspring quality rather than quantity, whereas agricultural practices affect both life history traits.

La mejora de la calidad de vida de las personas con lesión medular: la transición del centro rehabilitador a la vida cotidiana desde la perspectiva de los usuarios

El retorno a la vida cotidiana para una persona con lesión medular después del periodo de rehabilitación en régimen hospitalario, es un proceso difícil no exento de dificultades y nuevos retos personales. En este trabajo nos planteamos identificar aquellos factores más relevantes que contribuyen a mejorar su calidad de vida, desde la perspectiva de las propias personas afectadas. Hemos realizado dos grupos de discusión: uno formado por 12 personas con paraplejia y otro formado por 6 personas con tetraplejia. El análisis de contenido realizado indica que, para los participantes existen dos dimensiones relacionadas con su percepción de calidad de vida una vez salen del centro de rehabilitación: a) necesidad de atención al entorno más próximo y b) preparación para el mundo real. Concluimos señalando la importancia de realizar programas de rehabilitación integral, que incluyan, rehabilitación física, aprendizaje de habilidades que posibiliten el máximo de independencia y autonomía personal y trabajo de apoyo a la familia

Emprego da tomografia computadorizada na detecção de alterações das adrenais em doentes com tuberculose

Neste estudo foram avaliadas, por meio de tomografia computadorizada, as adrenais em indivíduos sem tuberculose (grupo 1 - G1) e com tuberculose (grupo 2 - G2). A dimensão ântero-posterior, a espessura e o comprimento das adrenais foram comparados no G1 e no G2. Foram também avaliadas a duração da doença com a ocorrência de alteração morfológica no G2, e a distribuição segundo o sexo, a idade e a cor da pele no G1 e no G2. Neste estudo houve diferença nas dimensões ântero-posterior e espessura da adrenal direita entre o G1 e o G2. Observou-se maior ocorrência do sexo masculino e de indivíduos de pele branca no G2. Não houve associação entre a duração da doença e a ocorrência de alteração morfológica no G2. Maior ocorrência da alteração morfológica tipo alargamento foi observada no G2. Os principais achados pela tomografia computadorizada, nos pacientes com tuberculose, foram alargamento da adrenal sem calcificação, alargamento da adrenal com calcificação puntiforme e calcificação de aspecto residual da adrenal.

Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children : Tracing the complexity of human postnatal steroidogenesis.

CONTEXT: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3-6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. OBJECTIVE: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. METHODS: We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. RESULTS: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. CONCLUSION: The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.

O valor da fase sem contraste na tomografia computadorizada do abdome

OBJETIVO: Determinar o valor agregado da fase sem meio de contraste da tomografia computadorizada do abdome em pacientes sem diagnóstico determinado ou em estadiamento tumoral. MATERIAIS E MÉTODOS: Estudo prospectivo e transversal em 100 pacientes consecutivos submetidos a tomografia computadorizada abdominal sem e com meio de contraste intravenoso. Dois examinadores avaliaram todos os exames, procurando estabelecer, através da fase com meio de contraste intravenoso (primeira análise) e posteriormente através da fase sem contraste (segunda análise), o diagnóstico principal e os secundários em função da indicação clínica do exame. Mediu-se a freqüência de mudança diagnóstica decorrente da análise combinada das fases pré- e pós-contraste intravenoso. Casos que tiveram mudança diagnóstica foram avaliados por especialistas clínicos para determinar se implicaria mudanças de conduta. RESULTADOS: Diagnósticos principal e secundário foram modificados em 1 e 18 casos, respectivamente (p = 1,000; p = 0,143). Os diagnósticos modificados foram: esteatose, definição de nódulo em adrenal, nefrolitíase, classificação de cistos renais e calcificação hepática. Nos casos em que a fase sem contraste modificou o diagnóstico, os especialistas mudaram sua conduta em 14/19 (73%) dos pacientes (p = 0,038). CONCLUSÃO: A fase sem contraste não modificou significativamente o diagnóstico principal ou secundário. Porém, as mudanças nos diagnósticos secundários influenciaram na conduta adotada pelos especialistas.

Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.

BACKGROUND: Pregnant women with asthma need to take medication during pregnancy. OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy. METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries. RESULTS: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

When the non-contrast-enhanced phase is unnecessary in abdominal computed tomography scans? A retrospective analysis of 244 cases

Objective: To evaluate the necessity of the non contrast-enhanced phase in abdominal computed tomography scans. Materials and Methods: A retrospective, cross-sectional, observational study was developed, evaluating 244 consecutive abdominal computed tomography scans both with and without contrast injection. Initially, the contrast-enhanced images were analyzed (first analysis). Subsequently, the observers had access to the non-contrast-enhanced images for a second analysis. The primary and secondary diagnoses were established as a function of the clinical indications for each study (such as tumor staging, acute abdomen, investigation for abdominal collection and hepatocellular carcinoma, among others). Finally, the changes in the diagnoses resulting from the addition of the non-contrast-enhanced phase were evaluated. Results: Only one (0.4%; p > 0.999; non-statistically significant) out of the 244 reviewed cases had the diagnosis changed after the reading of non-contrast-enhanced images. As the secondary diagnoses are considered, 35 (14%) cases presented changes after the second analysis, as follows: nephrolithiasis (10%), steatosis (3%), adrenal nodule (0.7%) and cholelithiasis (0.3%). Conclusion: For the clinical indications of tumor staging, acute abdomen, investigation of abdominal collections and hepatocellular carcinoma, the non-contrast-enhanced phase can be excluded from abdominal computed tomography studies with no significant impact on the diagnosis.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

Aplicação de um protocolo de espectroscopia por ressonância magnética das adrenais: experiência com mais de 100 casos

Objetivo: Avaliar um protocolo de espectroscopia por ressonância magnética (ERM) do próton de hidrogênio (1H) bidimensional (2D) disponível comercialmente (Siemens Medical Systems; Erlangen, Alemanha), aplicado para nódulos adrenais e diferenciação das massas (adenomas, feocromocitomas, carcinomas e metástases). Materiais e Métodos: Um total de 118 pacientes (36 homens e 82 mulheres), apresentando-se com 138 nódulos/massas adrenais, foi avaliado prospectivamente (média de idade: 57,3 ± 13,3 anos). Uma sequência de ERM-1H-PRESS-CSI (espectroscopia por resolução de ponto-imagem por desvio químico) multivoxel foi utilizada. Análise espectroscópica foi realizada da esquerda-direita, sentido crânio-caudal, usando três sequências sagitais, além de sequências axiais e coronais T2-HASTE. Os seguintes índices foram calculados: colina (Cho)/creatina (Cr), 4,0–4,3 ppm/Cr, lipídio (Lip)/Cr, Cho/Lip e lactato (Lac)/Cr. Resultados: ERM-1H-2D foi bem sucedida em 123 (89,13%) lesões. Os valores de sensibilidade e especificidade encontrados para as proporções e pontos de corte avaliados foram: Cho/Cr ≥ 1,2, sensibilidade de 100% e especificidade de 98,2% (diferenciação de adenomas e carcinomas de feocromocitomas e metástases); 4,0–4,3 ppm/Cr ≥ 1,5, 92,3% de sensibilidade, especificidade de 96,9% (diferenciação de carcinomas e feocromocitomas de adenomas e metástases); Lac/Cr ≤ –7,449, sensibilidade de 90,9% e especificidade de 77,8% (diferenciação de feocromocitomas contra carcinomas e adenomas). Conclusão: Os dados da ERM-1H-2D foram eficazes e permitiram a diferenciação entre massas adrenais e nódulos na maioria das lesões com diâmetro > 1,0 cm.

The experience of identity transformation process for people living with tetraplegia and paraplegia = El proceso de reconstrucción de la identidad de las personas afectadas de una paraplejia o tetraplejia

A spinal cord injury (SCI) is perceived as a source of biographical disruption, not only at a physical level but also in terms of people’s life stories, their motivation and their self-esteem. The aim of this study is to explore the factors that people with spinal cord injuries perceive as contributing to rebuilding their sense of self. Two focus groups were established from the SCIcommunity, one of which was made up of 14 people with paraplegia and the other of 9 people with tetraplegia. In addition, four individual interviews were conducted with the participants. The results of content analysis show that the two most prominent factors in the process of identity renegotiation are the partial transformation of the subject’s identity followed by a coming to terms with that new identity. To rebuild self-worth, the importance of finding a balance between change and continuity was identified. Renegotiation of identity after a spinal cord injury is a complex phenomenon that greatly influences the SCI individual’s quality of life perceptions. Reaching a balance between the changes experienced due to the injury and finding a sense of continuity can be either facilitated or obstructed by the economic, political, legal, architectural, and social context

Regulating Mechanisms of Gonadal and Pituitary Tumorigenesis in Mice Producing Human Chorionic Gonadotropin

Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are structurally and functionally similar glycoprotein hormones acting through the same luteinizing hormone chorionic gonadotropin receptor (LHCGR). The functions of LH in reproduction and hCG in pregnancy are well known. Recently, the expression of LHCGR has been found in many nongonadal tissues and cancers, and this has raised the question of whether LH/hCG could affect the function or tumorigenesis of these nongonadal tissues. We have also previously generated an hCG expressing mouse model presenting nongonadal phenotypes. Using this model it is possible to improve our understanding of nongonadal action of highly elevated LH/hCG. In the current study, we analyzed the effect of moderately and highly elevated hCG levels on male reproductive development and function. The main finding was the appearance of fetal Leydig cell (FLC) adenomas in prepubertal males. However, the development and differentiation of FLCs were not significantly affected. We also show that the function of hCG is different in FLCs and in adult Leydig cells (ALC), because in the latter cells hCG was not able to induce tumorigenesis. In FLCs, LHCGR is not desensitized or downregulated upon ligand binding. In this study, we found that the testicular expression of two G protein-coupled receptor kinases responsible for receptor desensitization or downregulation is increased in adult testis. Results suggest that the lack of LHCGR desensitization or downregulation in FLCs protect testosterone (Te) synthesis, but also predispose FLCs for LH/hCG induced adenomas. However, all the hCG induced nongonadal changes observed in male mice were possible to explain by the elevated Te level found in these males. Our findings indicate that the direct nongonadal effects of elevated LH/hCG in males are not pathophysiologically significant. In female mice, we showed that an elevated hCG level was able to induce gonadal tumorigenesis. hCG also induced the formation of pituitary adenomas (PA), but the mechanism was indirect. Furthermore, we found two new potential risk factors and a novel hormonally induced mechanism for PAs. Increased progesterone (P) levels in the presence of physiological estradiol (E2) levels induced the formation of PAs in female mice. E2 and P induced the expression and nuclear localization of a known cell-cycle regulator, cyclin D1. A calorie restricted diet was also able to prevent the formation of PAs, suggesting that obesity is able to promote the formation of PAs. Hormone replacement therapy after gonadectomy and hormone antagonist therapy showed that the nongonadal phenotypes observed in hCG expressing female mice were due to ovarian hyperstimulation. A slight adrenal phenotype was evident even after gonadectomy in hCG expressing females, but E2 and P replacement was able to induce a similar phenotype in WT females without elevated LH/hCG action. In conclusion, we showed that the direct effects of elevated hCG/LH action are limited only to the gonads of both sexes. The nongonadal phenotypes observed in hCG expressing mice were due to the indirect, gonadal hormone mediated effects of elevated hCG. Therefore, the gonads are the only physiologically significant direct targets of LHCGR signalling.

Targeted ablation of gonadotropin dependent endocrine tumors in transgenic mice through their luteinizing hormone receptor (LHR)

Gonadal somatic cell and adrenocortical endocrine tumors are rare. The incidence of adrenocortical carcinomas is only 1-2/1000000 a year. However, they are aggressive, especially in adulthood and currently surgery is the only curative treatment. Cytotoxic agents are in use in advanced cancers, but side effects and multidrug resistance are often problems. Thus there is a need for novel curative treatment methods. In contrast, ovarian granulosa cell tumors and testicular Leydig cell tumors are usually benign, especially at a younger age. The aim of the present thesis was to study a novel targeted treatment method through luteinizing hormone/chorionic gonadotropin receptor (LHCGR) in a transgenic mouse tumor model. The cytotoxic agent was lytic peptide Hecate-CGbeta conjugate where 23 amino acid Hecate, a synthetic form of honeybee venom melittin, was conjugated to 15 amino acid fragment of human chorionic gonadotropin β subunit. Lytic peptides are known to act only on negatively charged cells, such as bacteria and cancer cells and hereby, due to hCGbeta fragment, the conjugate is able to bind directly to LHCGR bearing cancer cells, saving the healthy ones. The experiments were carried out in inhibin-alpha-Simian Virus 40-T-antigen transgenic mice that are known to express LHCGR-bearing gonadal tumors, namely Leydig and granulosa cell tumors by 100% penetrance. If the mice are gonadectomized prepubertally they form adrenocortical tumors instead. Transgenic and wild type mice were treated for three consecutive weeks with control vehicle, Hecate or Hecate-CGbeta conjugate. GnRH antagonist or estradiol was given to a group of mice with or without Hecate-CGbeta conjugate to analyze the additive role of gonadotropin blockage in adrenocortical tumor treatment efficacy. Hecate-CGbeta conjugate was able to diminish the gonadal and adrenal tumor size effectively in males. No treatment related side effects were found. Gonadotropin blockage through GnRH antagonist was the best treatment in female adrenal tumors. The mode of cell death by Hecate-CGbeta conjugate was proven to be through necrosis. LHCGR and GATA-4 were co-expressed in tumors, where the treatment down-regulated their expression simultaneously, suggesting their possible use as tumor markers. In conclusion, the present thesis showed that Hecate-CGbeta conjugate targets its action selectively through LHCGR and selectively kills the LHCGR bearing tumor cells. It works both in gonadal somatic and in ectopic LHCGR bearing adrenal tumors. These results establish a more general principle that receptors expressed ectopically in malignant cells can be exploited in targeted cytotoxic therapies without affecting the normal healthy cells.

Actuación interdisciplinar en alteraciones por espina bífida en el pie

La malformación congénita conocida como Espina Bífida se caracteriza por la ausencia de fusión de la línea media posterior de la columna vertebral produciéndose una hernia del contenido del conducto vertebral (médula, meninges y raíces nerviosas). Este síndrome compromete múltiples sistemas del organismo, debiéndose tratar por un equipo multidisciplinar. A nivel del pie se producen deformidades tanto flácidas como espásticas con déficit motores radiculares (55%). Estos problemas estructurales provocaran alteraciones biomecánicas severas con sobrecargas a nivel plantar (33%). Si a esto añadimos alteraciones radiculares sensitivas, con insensibilidad en piernas y pies (60%), nos encontramos ante un paciente de riesgo susceptible de tratamientos preventivos y curativos podológicos. Las probabilidades de padecer una úlcera neuropática son grandes y el Podólogo debe prevenir o, en el peor de los casos, tratar el mal perforante plantar de una forma interdisciplinar. Preventivamente realizaremos quiropodias periódicas y exploración de sensibilidades, tanto exteroceptivas como propioceptivas. A nivel podológico trataremos de una forma integral la úlcera neuropática, incluyendo los drenajes y las"toilettes" quirúrgicas, y realizaremos tratamientos ortopodológicos complejos. En esta comunicación presentamos un caso típico de paciente afecto de Espina Bífida con alteraciones biomecánicas severas y úlcera con recorrido fistuloso, al cual realizamos un drenaje y confeccionamos una férula supramaleolar interna unilateral para redistribuir las presiones y evitar las sobrecargas.

Malacoplaquia intestinal

Malacoplakia is a chronic granulomatous disease of unknown origin. However immunodeficiency states (immunossuppressive medication, old people, renal transplantation, leukaemia, diabetes mellitus, malnutrition and others) have been associated with patients with malacoplakia. An infectious cause of malakoplakia is suggested by the finding of coliform bacteria in the phagolysosomes of macrophages. The histologic study is characterized by a infiltrate of large macrophages (Hansenmann cells) with pathognomonic inclusions containing siderocalcific structures (Michaelis-Gutmann bodies). Most of the cases reported in literature, involve the genitourinary tract, but other structures can be affected (brain, bone, adrenal glands, lymph nodes, intestine, and others). A 66-year-old man whith a abdominal mass, went to our hospital with a colonic tumour diagnosis. The patient was submitted to a surgery, with resection of the rigth colon. The disease was invading a portion of the retroperitoneal tissue that was removed. The histopatologic study showed the pathognomonic sign of malakoplakia (Hansenmann cells and Michaelis-Gutmann bodies). Norfloxacin have been used to the complementar treatment with total cure of the patient.