Metastatic organotropism: a brief overview.

Organotropism has been known since 1889, yet this vital component of metastasis has predominantly stayed elusive. This mini-review gives an overview of the current understanding of the underlying mechanisms of organotropism and metastases development by focusing on the formation of the pre-metastatic niche, immune defenses against metastases, and genomic alterations associated with organotropism. The particular case of brain metastases is also addressed, as well as the impact of organotropism in cancer therapy. The limited comprehension of the factors behind organotropism underscores the necessity for efficient strategies and treatments to manage metastases.

The physiological effects of a low-impact Bodyattack (TM) class / Caracterización fisiológica de una clase de Bodyattack (TM) de bajo impacto

OBJECTIVE: To estimate total energy expenditure and intensity of a low impact BodyattackTM session using combined heart rate and movement sensing technology. METHOD: Participants were 10 (8 males) normal-weight adults (33 ± 3 years-old). Maximal oxygen capacity and heart rate were determined by the performance on a treadmill maximal exercise test using indirect calorimetric method. Heart rate and energy expenditure values were monitored during a Bodyattack™ routine using a combined heart rate and movement sensor. The manufacturer's combined activity and heart rate algorithm was used to estimate Total and Physical activity energy expenditure. RESULTS: A 60 min low impact BodyattackTM session demands a Total energy expenditure of 469.4 ± 170.8 kcal at an average intensity of 64% of maximal heart rate, from which approximately 27.2 min are spent at moderate to vigorous physical activity intensities. Compared to a high impact BodyattackTM session as reported by the trademark company, Total energy expenditure was lower in the low impact option (-194.8 Kcal, p = 0.006), but no significant differences were found in average intensity (-9.4%, p = 0.707). CONCLUSION: Bodyattack™ routines performed at a low impact option may be sufficient to meet minimal recommendations for developing and maintaining cardiorespiratory fitness, if practiced beyond three days.week-1. Although appropriate for untrained individuals and those with orthopedic limitations, energy requirements of low impact Bodyattack™ may not be enough to elicit an effective weight loss

OBJETIVO: Estimar el gasto total de energía y la intensidad de una rutina de BodyattackTM de bajo impacto. MÉTODOS: Los participantes fueron 10 adultos de peso normal (33 ± 3 años). La potencia máxima de oxígeno y la frecuencia cardíaca (FC) se determinaron por el rendimiento en una prueba de ejercicio máxima utilizando el método calorimétrico indirecto. Los valores de la frecuencia cardíaca y del gasto total de energía se monitorearon durante una rutina utilizando un sensor combinado de frecuencia cardíaca y movimiento. RESULTADOS: Una clase de BodyattackTM de bajo impacto de 60 minutos exige un gasto total de energía de 469.4 ± 170.8 kcal a una intensidad promedio del 64% de la frecuencia cardíaca máxima, de los cuales 27.2 minutos se gastan en actividad física de intensidad moderada a vigorosa. En comparación con una clase de alto impacto, el gasto total de energía fue menor en la opción de bajo impacto (-194.8 Kcal, p = 0.006), pero no se encontraron diferencias en la intensidad promedio (-9.4%, p = 0.707). CONCLUSIÓN: Las clases de Bodyattack™ de bajo impacto pueden cumplir con las recomendaciones mínimas para desarrollar y mantener la aptitud cardiorrespiratoria, si se practican más de tres días por semana. Sin embargo, los requisitos de energía de Bodyattack ™ de bajo impacto pueden no provocar una pérdida de peso efectiva

Pherotype influences biofilm growth and recombination in Streptococcus pneumoniae.

In Streptococcus pneumoniae the competence-stimulating peptide (CSP), encoded by the comC gene, controls competence development and influences biofilm growth. We explored the influence of pherotype, defined by the two major comC allelic variants (comC1 and comC2), on biofilm development and recombination efficiency. Among isolates recovered from human infections those presenting comC1 show a higher capacity to form in vitro biofilms. The influence of pherotype on biofilm growth was confirmed by experiments with isogenic strains differing in their comC alleles. Biofilm architecture evaluated by confocal laser scanning microscopy showed that strains carrying comC1 form biofilms that are denser and thicker than those carrying the comC2 allele. Isogenic strains carrying the comC1 allele yielded more transformants than those carrying the comC2 allele in both planktonic and biofilm growth. Transformation assays with comC knockout strains show that ComD1 needs lower doses of the signaling peptide to reach the same biological outcomes. In contrast to mixed planktonic growth, within mixed biofilms inter-pherotype genetic exchange is less frequent than that occurring between bacteria of the same pherotype. Since biofilms are a major bacterial lifestyle, these observations may explain the genetic differentiation between populations with different pherotypes reported previously. Considering that biofilms have been associated with colonization our results suggest that strains carrying the comC1 allele may be more transmissible and more efficient at persisting in carriage. Both effects may help explain the higher prevalence of the comC1 allele in the pneumococcal population.

Body composition phenotypes and carotid intima-media thickness in 11-13-year-old children.

UNLABELLED: Early detection of impairment in vascular structure is an important clinical pursuit. However, it is unknown which measure of body composition best predicts vascular wall changes. We assess the differences in body composition among intima-media thickness (IMT) tertiles and determined which measures of body composition are associated with IMT in 385 children aged 11-13 years (196 girls). In this cross-sectional study, body mass index (BMI), waist circumference (WC), body fat mass (BFM), and trunk fat mass (TFM) from dual-energy radiographic absorptiometry and IMT through high-resolution ultrasonography were collected. Differences in body composition measures among IMT tertiles [low IMT (LIMT), ≤ 0.46 mm; middle IMT, 0.46-0.53 mm; higher IMT (HIMT), ≥0.53 mm] were assessed with ANOVA/ANCOVA after categorization. Regression analysis was used to assess the relationships between body composition and IMT. The groups were similar for sex, age, and maturity (p > 0.05). As compared with LIMT group, subjects with HIMT had higher mean values of BMI, BFM, TFM, and WC (p < 0.05). Significant differences were found for WC even when controlling for BMI (p < 0.05). Combining all subjects, IMT was significantly correlated to BMI, BFM, TFM, and WC (p < 0.05). In multiple regression, WC was the only predictor of IMT (ß = 0.22, p < 0.001). CONCLUSION: Differences exist in body composition variables among IMT tertiles. In the overall model, WC was the only obesity-related predictor of increased IMT in 11-13-year-old children.

The impact of exercise training on liver transplanted familial amyloidotic polyneuropathy (FAP) patients.

BACKGROUND: Liver transplantation is nowadays the only effective answer to adjourn the outcome of functional limitations associated with familial amyloidotic polyneuropathy (FAP), a neurodegenerative disease characterized by sensory and motor polyneuropathies. Nevertheless, there is a detrimental impact associated with the after-surgery period on the fragile physical condition of these patients. Exercise training has been proven to be effective on reconditioning patients after transplantation. However, the effects of exercise training in liver transplanted FAP patients have not been scrutinized yet. METHODS: The study aimed to evaluate the effects of a 24-week exercise training program (supervised or home-based) on body composition, muscle strength, and walking capacity of liver transplanted FAP patients. To fulfill this goal, a sample corresponding to 33% of all FAP patients who undergone a liver transplantation in the area of Lisbon between January 2006 and December 2008 were followed over time. Three evaluation periods were accomplished: M1 (pre-exercise training period), M2 (immediate post-exercise training period), and M3 (24 weeks after M2). The former allowed an assessment of the impact of detraining in these patients. RESULTS: The exercise training program improved body composition (lean mass and total body skeletal muscle mass), weight, and walking capacity. The improvements were more pronounced within the patients with supervised exercise training compared with the patients on the home-based program. In general, the benefits of the exercise training perdure even after a 24-week detraining period. CONCLUSIONS: Exercise training results in significant improvements on the physical condition of liver transplanted FAP patients.

Prophage spontaneous activation promotes DNA release enhancing biofilm formation in Streptococcus pneumoniae.

Streptococcus pneumoniae (pneumococcus) is able to form biofilms in vivo and previous studies propose that pneumococcal biofilms play a relevant role both in colonization and infection. Additionally, pneumococci recovered from human infections are characterized by a high prevalence of lysogenic bacteriophages (phages) residing quiescently in their host chromosome. We investigated a possible link between lysogeny and biofilm formation. Considering that extracellular DNA (eDNA) is a key factor in the biofilm matrix, we reasoned that prophage spontaneous activation with the consequent bacterial host lysis could provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that phage-infected bacteria are more proficient at forming biofilms, that is their biofilms are characterized by a higher biomass and cell viability. The presence of phage particles throughout the lysogenic strains biofilm development implicated prophage spontaneous induction in this effect. Analysis of lysogens deficient for phage lysin and the bacterial major autolysin revealed that the absence of either lytic activity impaired biofilm development and the addition of DNA restored the ability of mutant strains to form robust biofilms. These findings establish that limited phage-mediated host lysis of a fraction of the bacterial population, due to spontaneous phage induction, constitutes an important source of eDNA for the S. pneumoniae biofilm matrix and that this localized release of eDNA favors biofilm formation by the remaining bacterial population.

Pherotypes are driving genetic differentiation within Streptococcus pneumoniae.

BACKGROUND: The boundaries of bacterial species and the mechanisms underlying bacterial speciation are matters of intense debate. Theoretical studies have shown that recombination acts as a strong cohesive force preventing divergence in bacterial populations. Streptococcus pneumoniae populations have the telltale signs of high recombination with competence implicated as the major driving force behind gene exchange. Competence in S. pneumoniae is triggered by a quorum-sensing mechanism controlled by the competence-stimulating peptide pheromone. RESULTS: We studied the distribution of the two major pherotypes in the pneumococcal population and their association with serotype, antimicrobial resistance and genetic lineage. Using multilocus sequence data we evaluated pherotype influence on the dynamics of horizontal gene transfer. We show that pherotype is a clonal property of pneumococci. Standard population genetic analysis and multilocus infinite allele model simulations support the hypothesis that two genetically differentiated populations are defined by the major pherotypes. CONCLUSION: Severe limitations to gene flow can therefore occur in bacterial species in the absence of geographical barriers and within highly recombinogenic populations. This departure from panmixia can have important consequences for our understanding of the response of pneumococci to human imposed selective pressures such as vaccination and antibiotic use.

The state of the health workforce in Portugal.

This paper discusses the state of the health workforce in Portugal's mainland during the past four decades. Healthcare workers represent 3.76% of the Portuguese workforce. All health professional groups significantly increased since 1960. Growth has been continuous for hospital physicians and nurses in general, as well as for primary care nurses. Primary care physicians are an exception, growing until the late 1970s but steadily decreasing afterwards. The density of physicians per 1000 inhabitants is above the European average. For nurses, Portugal is at the lowest European limit. However, the regional distribution of nurses, and also of pharmacists, across the country is more equitable than for physicians. The number of workers employed by the Health Ministry has grown by 44.6% between 1985 and 2004, with 127 013 employees registered in 2004. There has also been a marked increase in the number of female employees. Only 23.6% of healthcare workers employed by the Health Ministry, work at primary care level. Data on the private sector is insufficient in spite of its rising importance. The right number and mix of healthcare workers for an optimal healthcare system performance is a complex question and answering it requires an adequate information system. Portugal does not have such a system yet.

Hepatocyte growth factor and its receptor are required for malaria infection.

Plasmodium, the causative agent of malaria, must first infect hepatocytes to initiate a mammalian infection. Sporozoites migrate through several hepatocytes, by breaching their plasma membranes, before infection is finally established in one of them. Here we show that wounding of hepatocytes by sporozoite migration induces the secretion of hepatocyte growth factor (HGF), which renders hepatocytes susceptible to infection. Infection depends on activation of the HGF receptor, MET, by secreted HGF. The malaria parasite exploits MET not as a primary binding site, but as a mediator of signals that make the host cell susceptible to infection. HGF/MET signaling induces rearrangements of the host-cell actin cytoskeleton that are required for the early development of the parasites within hepatocytes. Our findings identify HGF and MET as potential targets for new approaches to malaria prevention.