Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal children: Comparison of definitions.

BACKGROUND AND AIMS: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers. METHODS AND RESULTS: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5-10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR. CONCLUSION: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations.

Mechanisms of stress, energy homeostasis and insulin resistance in European adolescents--the HELENA study.

BACKGROUND AND AIMS: Stress is hypothesized to facilitate the development of obesity, whose the foundations are already set during childhood and adolescence. We investigated the relationship between the stress-system, selected mechanisms of energy homeostasis and insulin resistance (IR) in a sample of European adolescents. METHODS AND RESULTS: Within HELENA-CSS, 723 adolescents (12.5-17.5 years) from 10 European cities provided all the necessary data for this study. Fasting blood samples were collected for cortisol, leptin, insulin and glucose analysis. HOMA-IR was calculated from insulin and glucose concentrations. Adolescents' body fat (BF) %, age and duration of exclusive breastfeeding were assessed. For boys and girls separately, the relationship of cortisol with leptin, insulin, glucose and HOMA-IR was examined by computing Pearson correlation coefficients and Hierarchical Linear Models (HLMs), with 'city' as cluster unit, adjusting for age, BF% and duration of exclusive breastfeeding. In boys, Pearson correlation coefficients illustrated positive correlations of cortisol with insulin (r = 0.144; p = 0.013), glucose (r = 0.315; p < 0.001) and HOMA-IR (r = 0.180; p = 0.002), whilst in girls, this positive relationship was observed for leptin (r = 0.147; p = 0.002), insulin (r = 0.095; p = 0.050) and HOMA-IR (r = 0.099; p = 0.041), but not for glucose (r = 0.054; p = 0.265). Observed associations were independent of adolescents' age, BF% and duration of exclusive breastfeeding after computing HLMs. CONCLUSION: This study suggests that the stress-system is positively related to mechanisms of energy homeostasis and IR in European adolescents, and reveals a potential small gender difference in this relationship. The hypothesis that stress might facilitate the development of obesity during adolescence is supported.

Motor Reaction Time, Sarcopenia and Functional Skills in Elderly Women: A Cross-Sectional Study.

IMPORTANCE: Aging generates changes over the years. Because of this, the musculoskeletal system is directly degraded and suffer deficits in its performance in elderly patients with Sarcopenia, as this condition is characterized by a decrease in muscle mass and function. OBJECTIVE: Correlate the motor reaction time and functional skills of non-sarcopenic, pre-sarcopenic and sarcopenic elderly women, and analyze influence on the risk of falls. DESIGN: Cross-sectional observational analytical study, following the methodological strategies of STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), carried out under the approval of the Research Ethics Committee of the Unievangélica University, no. 3.694.235/2019. SETTING: Participants were evaluated regarding: cognitive status, level of physical activity, fear of falling, body composition, motor reaction time, static and dynamic balance, gait kinetics, strength and endurance of the lower limbs and finally handgrip strength. PARTICIPANTS: A total of 59 volunteer elderly women were assessed following the diagnostic criteria for sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: The results show that there was a greater difference in motor reaction time between the non-sarcopenic and sarcopenic elderly women due to the executing organ being damaged by the presence of sarcopenia, causing motor response to slowdown. Functional deficit, fear of falling and greater risk of falls were observed in the sarcopenic group, under the harmful influence of increased motor reaction time. CONCLUSION: Sarcopenic elderly women present increased motor reaction time, that is, slowed motor responses due to decreased muscle mass, strength and impaired musculature, which generate functional deficits that contribute to an increased risk of falls.

Association between the FTO rs9939609 polymorphism and leptin in European adolescents: a possible link with energy balance control. The HELENA study.

We examined the association between the FTO rs9939609 polymorphism and serum leptin concentrations in adolescents. The FTO rs9939609 polymorphism was genotyped, and fasting serum leptin and insulin were measured in 655 European adolescents (365 females) aged 14.6 ± 1.2 years. We measured weight, height, triceps and subscapular skinfolds and waist circumference, and body fat percentage was calculated. Sex, pubertal status, center, physical activity (accelerometry), total or central adiposity and serum insulin concentrations were entered as confounders in the analyses. The minor A allele of the FTO rs9939609 was significantly associated with higher serum leptin concentrations independently of potential confounders including adiposity (+3.9 ng ml(-1) per risk allele (95% confidence interval: 2.0, 5.9); adjusted P < 0.001). These findings could link the FTO gene with serum leptin and consequently with the control of energy balance. Leptin could be a possible intermediary contributing to the association between the FTO rs9939609 polymorphism and adiposity.

Presence of the metabolic syndrome in obese children at prepubertal age.

BACKGROUND/AIMS: There is a strong debate on the diagnosis and early phenotypic expression of the metabolic syndrome in children. The aim of the present study was to examine the frequency of the metabolic syndrome using various definitions in obese prepubertal and pubertal children. METHODS: 478 (213 females and 265 males) obese children were recruited in three provinces of Spain. Blood pressure (BP), waist circumference, and weight and height were measured, and body mass index was calculated. Glucose, insulin, high-density lipoprotein cholesterol and triacylglycerols were determined. We classified the children according to seven different proposed definitions of the metabolic syndrome. RESULTS: Regardless of the definition used, the prevalence of the metabolic syndrome (8.3-34.2%) was relatively high in obese children in the prepubertal period as well as in pubertal children (9.7-41.2%). We performed a principal-factor analysis to explain correlations among features of the metabolic syndrome and found that glucose metabolism (factor 1), dyslipidemia (factor 2) and obesity/BP (factor 3) explained 72% of the total variance. CONCLUSION: Irrespective of the classification used, the metabolic syndrome is not only present in pubertal but also in prepubertal children. International definitions of the metabolic syndrome should also consider criteria specific for children in the prepubertal period, i.e. children aged <10 years.

MicroHikari3D: an automated DIY digital microscopy platform with deep learning capabilities.

A microscope is an essential tool in biosciences and production quality laboratories for unveiling the secrets of microworlds. This paper describes the development of MicroHikari3D, an affordable DIY optical microscopy platform with automated sample positioning, autofocus and several illumination modalities to provide a high-quality flexible microscopy tool for labs with a short budget. This proposed optical microscope design aims to achieve high customization capabilities to allow whole 2D slide imaging and observation of 3D live specimens. The MicroHikari3D motion control system is based on the entry level 3D printer kit Tronxy X1 controlled from a server running in a Raspberry Pi 4. The server provides services to a client mobile app for video/image acquisition, processing, and a high level classification task by applying deep learning models.

Fast Monte Carlo simulation on a voxelized human phantom deformed to a patient.

PURPOSE: A method for performing fast simulations of absorbed dose using a patient's computerized tomography (CT) scan without explicitly relying on a calibration curve is presented. METHODS: The method is based on geometrical deformations performed on a standard voxelized human phantom. This involves spatially transforming the human phantom to align it with the patient CT image. Since the chemical composition and density of each voxel are given in the phantom data, a calibration curve is not used in the proposed method. For this study, the Monte Carlo (MC) code PENELOPE has been used as the simulation of reference. The results obtained with PENELOPE simulations are compared to those obtained with PENFAST and with the collapsed cone convolution algorithm implemented in a commercial treatment planning system. RESULTS: The comparisons of the absorbed doses calculated with the different algorithms on two patient CTs and the corresponding deformed phantoms show a maximum distance to agreement of 2 mm, and in general, the obtained absorbed dose distributions are compatible within the reached statistical uncertainty. The validity of the deformation method for a broad range of patients is shown using MC simulations in random density phantoms. A PENFAST simulation of a 6 MV photon beam impinging on a patient CT reaches 2% statistical uncertainty in the absorbed dose, in a 0.1 cm3 voxel along the central axis, in 10 min running on a single core of a 2.8 GHz CPU. CONCLUSIONS: The proposed method of the absorbed dose calculation in a deformed voxelized phantom allows for dosimetric studies in the geometry of a patient CT scan. This is due to the fact that the chemical composition and material density of the phantom are known. Furthermore, simulation using the phantom geometry can provide dosimetric information for each organ. The method can be used for quality assurance procedures. In relation to PENFAST, it is shown that a purely condensed-history algorithm (class I) can be used for absorbed dose estimation in patient CTs.

The impact of hip fracture on health-related quality of life and activities of daily living: the SPARE-HIP prospective cohort study.

PURPOSE: The medical morbidity and mortality associated with neck of femur fractures is well-documented, whereas there is limited data for patient-reported outcomes. The aim of this study was to characterize the impact of neck of femur fractures on activities of daily living and patient-reported health-related quality of life. METHODS: Design and participants: Multicentric prospective cohort study. Consecutive sample patients with fragility hip fracture over 50 years old admitted in 48 hospitals in Spain. OUTCOMES: daily living activity function (Barthel Index) and health-related quality of life (EQ-5D) pre-fracture, admission to hospital and at 1- and 4-month follow-up post-fracture. STATISTICS: Barthel and EQ-5D over time are described as mean (SD) and median (interquartile range). RESULTS: A total of 997 patients were recruited at baseline with 4-month outcomes available for, and 856 patients (89.5%). Barthel Index fell from 78.77 (23.75) at baseline to 43.62 (19.86) on admission to hospital with the fracture. Scores partially recovered to 54.89 (25.40) and 64.09 (21.35) at 1- and 4-month post-fracture, respectively. EQ-5D fell from a median of 0.75 (0.47-0.91) to - 0.01 (- 0.03 to 0.51) on admission. Partial recovery was observed again to (0.51 (- 0.06 to 0.67)) and (0.60 (0.10 to 0.80)) at 1- and 4-month post-fracture, respectively. CONCLUSIONS: Hip fracture results in a large decline in the ability to perform activities of daily living and patient-reported health-related quality of life with only partial recovery amongst survivors 4-month post-fracture.

Molecular profiling of docetaxel cytotoxicity in breast cancer cells: uncoupling of aberrant mitosis and apoptosis.

Among microtubule-targeting agents, docetaxel has received recent interest owing to its good therapeutic index. Clinical trials have underlined its potential for the treatment of advanced breast cancer, although little is known about its molecular mode of action in this context. We characterized the molecular changes induced by docetaxel in two well-known human breast carcinoma cell lines. Two mechanisms of action according to drug concentration were suggested by a biphasic sensitivity curve, and were further validated by cell morphology, cell cycle and cell death changes. Two to four nanomolar docetaxel induced aberrant mitosis followed by late necrosis, and 100 nM docetaxel induced mitotic arrest followed by apoptosis. Passing through mitosis phase was a requirement for hypodiploidy to occur, as shown by functional studies in synchronized cells and by combining docetaxel with the proteasome inhibitor MG132. Transcriptional profiling showed differences according to cell line and docetaxel concentration, with cell cycle, cell death and structural genes commonly regulated in both cell lines. Although p53 targets were mainly induced with low concentration of drug in MCF7 cells, its relevance in the dual mechanism of docetaxel cytotoxicity was ruled out by using an isogenic shp53 cell line. Many of the genes shown in this study may contribute to the dual mechanism by which docetaxel inhibits the growth of breast cancer cells at different concentrations. These findings provide a basis for rationally enhancing docetaxel therapy, considering lower concentrations, and better drug combinations.

Zinc supplementation in infants with asymmetric intra uterine growth retardation; effect on growth, nutritional status and leptin secretion.

OBJECTIVES: To analyse the effect of zinc supplementation in growth and nutritional status of a homogeneous group of newborns with intra uterine growth retardation and asymmetric growth. The effect of changes of zinc status on growth and leptin serum concentrations was also analysed. POPULATION AND METHODS: A double blind, randomised clinical trial was designed in order to detect differences in growth between zinc and placebo groups during the first 6 months of life. 31 infants were included either to the zinc group (n = 14) (38.8+/-1.4 weeks GA, 2,171+/-253 g body weight) or the placebo group (n = 17) (38.9+/-1.1 weeks GA, 2,249+/-220 g body weight). The zinc group received a supplement of 3 mg elemental zinc per day (as zinc sulphate). RESULTS: There were not significant differences between groups for anthropometric measurements through the study period. We found a significant effect of the study group, in hair zinc concentrations, but not in serum zinc concentrations; post-hoc comparisons for hair zinc revealed that there were significant differences between groups at 1, 2, and 6 months of age. Changes in serum and hair zinc concentrations from baseline to 6 months, showed significant correlations with changes in weight/age and length/age z-scores, in the supplement group. Changes in leptin serum concentrations during follow-up, showed significant correlations with changes in sum of 4 skinfolds and weight/age z-score, in the placebo group. Changes in hair zinc concentration through the study period showed significant correlations with changes in leptin serum concentrations from baseline to 6 months of follow-up. CONCLUSIONS: In a homogeneous group of intra uterine growth retardation infants with asymmetric growth, 3 mg/day zinc supplementation do not show significant improvements in weight and length growth. Changes in zinc status were related with changes in weight and length during the first 6 months of life. Changes in leptin serum concentrations were related with changes in the anthropometric indices of body fat accretion.

Metabolic risk-factor clustering estimation in obese children.

The purpose of this study was to apply the new approach for Metabolic Individual Risk-factor And Clustering Estimation (MIRACLE) score in a group of Spanish obese children and adolescents and to describe its relationship with other metabolic risk factors. 153 children with simple obesity were studied: 79 males and 74 females, mean age 11.2 +/- 2.2. Obesity was defined when BMI was higher than the age and sex specific equivalent to 30 kg/m2 in adults. MIRACLE score included: family history (early cardiovascular disease, type 2 diabetes, and hypertension), individual history (small for gestational age and ethnic origin), clinical features (BMI, waist circumference > 90th percentile and blood pressure > 95th percentile) and metabolic abnormalities (glucose intolerance or type 2 diabetes). It was assigned a value of 1 to "presence" and 0 to" absence" in every patient. The children were considered as having metabolic risk when at least 5 items were present. Triglycerides, HDL-cholesterol, apolipoprotein B, apolipoprotein A1, glucose and HOMA index, were measured too. The most frequent clinical features of MIRACLE score were: excess waist circumference (95.4%) and hypertension (41.8%). Family history criteria were frequent (55.3% for type 2 diabetes, 39.1% for hypertension and 31.3% for early cardiovascular disease). Individual risk factors were not frequent. Glucose intolerance was detected in 22.2% of the obese patients. A MIRACLE score > or = 5 was found in 37.4% of the children studied, being associated with a significant risk of dyslipidemia (triglycerides, p = 0.040; HDL-cholesterol, p = 0.006; LDL-cholesterol p = 0.038; apolipoprotein B, p = 0.008) only in females. In conclusion, the MIRACLE score is useful in order to detect metabolic risk in obese children but it seems necessary to improve the score, by including other features of the metabolic syndrome like lipid profile or indirect indicators of insulin resistance.

Parasitism by Monogenoidea in Piaractus mesopotamicus (Characiformes, Characidae) cultivated in Paraná River (Brazil).

This study investigated the occurrence, prevalence, mean abundance and mean intensity of monogenoidean parasites in Piaractus mesopotamicus farmed in cages in the reservoir of the Itaipu Hydroelectric Power Station, Paraná River, Brazil. The parasite distribution pattern and the correlation of prevalence and abundance with the total length of hosts were also investigated. Four monogenoidean species were collected: Anacanthorus penilabiatus, A. toledoensis, Mymarothecium ianwhitingtoni and M. viatorum. All the parasites collected in P. mesopotamicus showed the typical aggregated distribution pattern, and the abundance and the prevalence did not shown any correlation with the total length of hosts.

Association of telomere length with IL-6 levels during an obesity treatment in adolescents: interaction with the-174G/C polymorphism in the IL-6gene.

BACKGROUND: Shorter telomeres have been associated with elevated risk for age-related diseases. However, little is known about the biomarker role of telomere length (TL) for predicting inflammation and glucose alterations. OBJECTIVE: The objective of this research is to evaluate the association between TL, inflammatory markers and glucose levels after a 2-month weight-loss programme in obese adolescents. METHODS: Telomere length was measured using a quantitative polymerase chain reaction in 66 obese adolescents aged 12-17 years (51% men) from the EVASYON programme. The adolescents were genotyped for the polymorphism -174G/C (rs1800795) in the IL-6gene, and anthropometric and biochemical markers as well as inflammatory cytokines were analysed. RESULTS: Multiple-adjusted models showed that longer telomeres at baseline were associated with a higher reduction in glucose (B = -4.08, 95% confidence interval: -6.66 to -1.50) and IL-6 (B = -1.03, 95% confidence interval: -2.01 to -0.05) serum levels after 2 months of the weight-loss treatment. The -174G/C polymorphism modulated the association between basal TL and changes in IL-6 (P interaction = 0.029). Thus, subjects with the GG + GC genotype and with longer telomeres showed a higher decrease in IL-6 levels than CC homozygotes. CONCLUSION: Longer telomeres are associated with an improvement in glucose tolerance and inflammation after a weight-loss programme in obese adolescents. Moreover, the -174G/C polymorphism may influence the relationship between TL and IL-6 changes.

Diversity of metabolic syndrome risk factors in obese children and adolescents.

The aim of this study was to investigate the frequency of metabolic syndrome (MS) variables in a group of spanish obese children and adolescents, to asses MS prevalence in this population and to describe it's relationship with other metabolic risk factors. 103 children were studied : 54 male and 49 female, mean age 10.08+/-2.3 with exogenous obesity. Obesity was defined when BMI was higher than the age and sex specific equivalent to 30 kg/m(2) in adults. MS variables considered were waist circumference, blood pressure, fasting blood triglycerides, fasting glucose/insulin and HDL-cholesterol. The children were considered as having the MS when three or more characteristics showed abnormal values according to Cook and De Ferranti definitions. HOMA index, ApoB and ApoA1 were studied too. The most frequent features of the metabolic syndrome were excess waist circumference and hypertension. The MS markers with the lowest frequency were dyslipidemia and fasting hyperglicemia. MS prevalence was 29,9% (Cook et al. criteria) and 50% (De Ferranti et al. criteria). Fasting insulin and HOMA index values increased significantly (p < 0.05) when three or more abnormalities of the MS variables were present. Apo B increased significantly only in females (p < 0.05) and Apo Al decreased significantly (p < 0.05) in both sexes when MS was present. Adequate metabolic syndrome risk factors criteria, mainly cut-off values, need to be defined in the European paediatric population.

Treadmill walking differently affects body composition and metabolic parameters of female rats from normal or small litters.

This work assessed whether walking affects bodily development and metabolic parameters of female rats raised in small litters (three pups, group S) or control litters (nine pups, group C). After weaning, some of the rats had five sessions per week of a 30-min treadmill walking (CE and SE), while the others remained sedentary (CS and SS) until the age of 120 days. Exercise caused a reduction of body weight (CS/CE = 1.18), Lee index (CS/CE = 1.04), fasting blood glucose (CS/CE = 1.35), mesenteric (CS/CE = 1.23), and ovarian fat (CS/CE = 1.33) in CE, but only glucose was decreased in SE (SS/SE = 1.16). The diameter of adipocytes decreased to a half in the small-litter groups. Exercise increased subcutaneous (CS/CE = 0.88 and SS/SE = 0.71), but decreased retroperitoneal adipocytes (CS/CE = 1.2 and SS/SE = 1.3). Litter size reduction had little impact on females at the age of 120 days, but the light physical activity seemed insufficient to counteract all the effects of lactational overfeeding. On the other hand, pups from exercised mothers had a decrease in their biometric and glycemic indexes, demonstrating the transgenerational action of regular, although light, exercise.

The homeoprotein SIX1 controls cellular senescence through the regulation of p16INK4A and differentiation-related genes.

Cellular senescence is an antiproliferative response with essential functions in tumor suppression and tissue homeostasis. Here we show that SIX1, a member of the SIX family of homeobox transcriptional factors, is a novel repressor of senescence. Our data show that SIX1 is specifically downregulated in fibroblasts upon oncogenic stress and other pro-senescence stimuli, as well as in senescent skin premalignant lesions. Silencing of SIX1 in human fibroblasts suffices to trigger senescence, which is mediated by p16INK4A and lacks a canonical senescence-associated secretory phenotype. Interestingly, SIX1-associated senescence is further characterized by the expression of a set of development and differentiation-related genes that significantly overlap with genes associated with SIX1 in organogenesis or human tumors, and show coincident regulation in oncogene-induced senescence. Mechanistically, we show that gene regulation by SIX1 during senescence is mediated, at least in part, by cooperation with Polycomb repressive complexes. In summary, our results identify SIX1, a key development regulator altered in human tumors, as a critical repressor of cellular senescence, providing a novel connection between senescence, differentiation and tumorigenesis.

Homeostatic model assessment (HOMA) index cut-off values to identify the metabolic syndrome in children.

The aim of the study was to establish the best cut-off value for the homeostatic model assessment (HOMA) index in identifying children and adolescents with the metabolic syndrome. The study included 72 non-obese and 68 obese children aged 7 to 16 years. Obesity is defined using the criteria proposed by Cole et al., being included as metabolic syndrome variables waist circumference, systolic blood pressure, diastolic blood pressure and seric values of glucose, uric acid, fasting insulin, leptin, triglycerides and HDL-cholesterol. Children were considered as having the metabolic syndrome when four or more characteristics showed abnormal values. The HOMA index was calculated as the product of the fasting plasma insulin level (microU/mL) and the fasting plasma glucose level (mmol/L), divided by 22.5. HOMA index cut-offs from the 5th to the 95th percentile were used. A receiver operating characteristic (ROC) curve was generated using the different HOMA cut-offs for the screening of the metabolic syndrome. The areas under the ROC curve, 95% confidence intervals, and the point to the ROC curve closest to 1, were calculated. The area under the ROC curve was 0.863 (95% C.I.: 0.797, 0.930). The point closest to 1 corresponds to the 60th percentile of the HOMA index distribution in our sample. HOMA index value at the 60th percentile was 2.28. Cut-off values corresponding to a range of HOMA index from the 50 to the 75 percentile, showed similar distances to 1. HOMA index values for percentiles 50 to 75 ranged from 2.07 to 2.83. In conclusion, HOMA index could be a useful tool to detect children and adolescents with the metabolic syndrome. HOMA cut-off values need to be defined in the paediatric population; however, values near to 3 seem to be adequate.

Indicadores de sustentabilidade socioambiental de pisciculturas familiares em área de Mata Atlântica, no Vale do Ribeira - SP / Social and Environmental Indicators of Family Fish Farms in the Atlantic Forest area in the Ribeira Valley - SP

O objetivo deste trabalho consistiu na aplicação de indicadores socioambientais em pisciculturas familiares localizadas na região do Vale do Ribeira, em área de Mata Atlântica, no sudoeste do estado de São Paulo. Para isso, foram identificadas 84 propriedades. Dessas, 40 foram selecionadas como unidades amostrais. Entre as principais características identificadas, 32% possuem lâmina d'água inferior a cinco hectares, com viveiros escavados em sistema semi-intensivo, 58% utilizam mão de obra familiar e 23% apontam a ausência de assistência técnica especializada como o principal problema enfrentado. A tilápia-do-nilo (Oreochromis niloticus) representa 57% das espécies produzidas em sistemas de monocultivo ou policultivo. Contudo, as pisciculturas familiares são classificadas como sistemas produtivos de pequeno porte, com destaque para a necessidade de adequação de recursos naturais, da capacidade de gestão e da eficiência das práticas de produção. Os indicadores sociais variaram de 0,75 a 1,00 para equidade salarial, proporção de autoemprego, uso de mão de obra local, inclusão de gênero e inclusão etária, demonstrando a capacidade que a aquicultura tem para auxiliar no desenvolvimento social local, por meio da geração de emprego e renda.(AU)

The objective of this work was to apply socioenvironmental indicators in family fish farms located in the Ribeira Valley region, Atlantic Forest area, southwest of São Paulo state, Brazil. Thus, we identified 84 production units. Of these, we selected 40 as sample units. Among the main characteristics identified, 32% have water depth of less than five hectares with excavated ponds in semi-intensive system, 58% use family labor and 23% report the lack of specialized technical assistance as the main problem faced. The Nile tilapia (Oreochromis niloticus) represents 57% of the species produced in monoculture or polyculture systems. Therefore, family fish farms are classified as small production systems with emphasis on the need to adapt natural resources, management capacity and efficiency of production practices. Social indicators ranged from 0.75 to 1.00 for salary equity, proportion of self-employment, use of local labor, gender inclusion and age inclusion, demonstrating the ability of aquaculture to assist local social development through job and income generation.(AU)

Lysyl oxidase-like 2 (LOXL2) and E47 EMT factor: novel partners in E-cadherin repression and early metastasis colonization.

Epithelial-mesenchymal transition (EMT) has been associated with increased aggressiveness and acquisition of migratory properties providing tumor cells with the ability to invade into adjacent tissues. Downregulation of E-cadherin, a hallmark of EMT, is mediated by several transcription factors (EMT-TFs) that act also as EMT inducers, among them, Snail1 and the bHLH transcription factor E47. We previously described lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, as a Snail1 regulator and EMT inducer. Here we show that LOXL2 is also an E47-interacting partner and functionally collaborates in the repression of E-cadherin promoter. Loss and gain of function analyses combined with in vivo studies in syngeneic breast cancer models demonstrate the participation of LOXL2 and E47 in tumor growth and their requirement for lung metastasis. Furthermore, LOXL2 and E47 contribute to early steps of metastatic colonization by cell and noncell autonomous functions regulating the recruitment of bone marrow progenitor cells to the lungs and by direct transcriptional regulation of fibronectin and cytokines TNFα, ANG-1 and GM-CSF. Moreover, fibronectin and GM-CSF proved to be necessary for LOXL2/E47-mediated modulation of tumor growth and lung metastasis.

EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination.

The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previously unknown long noncoding (lnc) RNAs from EFNA3 locus and these lncRNA caused Ephrin-A3 protein accumulation. Ephrins are cell surface proteins that regulate diverse biological processes by modulating cellular adhesion and repulsion. Mounting evidence implicates deregulated ephrin function in multiple aspects of tumor biology. We demonstrate that sustained expression of both Ephrin-A3 and novel EFNA3 lncRNAs increased the metastatic potential of human breast cancer cells, possibly by increasing the ability of tumor cells to extravasate from the blood vessels into surrounding tissue. In agreement, we found a strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients. Taken together, our results suggest that hypoxia could contribute to metastatic spread of breast cancer via HIF-mediated induction of EFNA3 lncRNAs and subsequent Ephrin-A3 protein accumulation.