Implementation and design of customized ex vivo machine perfusion. Analysis of its first results.

The lack of organs available for transplantation is a global problem. The high mortality rates on the waiting list and the high number of discarded livers are reasons to develop new tools in the preservation and transplantation process. New tools should also be available for low-income countries. This article reports the development of customized normothermic machine perfusion (NMP). An ex vivo dual perfusion machine was designed, composed of a common reservoir organ box (CRO), a centrifugal pump (portal system, low pressure), and a roller pump (arterial system, high pressure). Porcine livers (n = 5) were perfused with an oxygenated normothermic (37℃) strategy for 3 hours. Hemodynamic variables, metabolic parameters, and bile production during preservation were analyzed. Arterial and portal flow remain stable during perfusion. Total bilirubin production was 11.25 mL (4-14.5) at 180 minutes. The median pH value reached 7.32 (7.25-7.4) at 180 minutes. Lactate values decreased progressively to normalization at 120 minutes. This perfusion setup was stable and able to maintain the metabolic activity of a liver graft in a porcine animal model. Design and initial results from this customized NMP are promising for a future clinical application in low-income countries.

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Association between breast cancer risk and disease aggressiveness: Characterizing underlying gene expression patterns.

The association between breast cancer risk defined by the Tyrer-Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5-year TC and disease aggressiveness and then characterized underlying molecular processes. In a case-only study (n = 2474), we studied the association of TC with molecular subtypes and tumor characteristics. In a subset of patients (n = 672), we correlated gene expression to TC and computed a low-risk TC gene expression (TC-Gx) profile, that is, a profile expected to be negatively associated with risk, which we used to test for association with disease aggressiveness. We performed enrichment analysis to pinpoint molecular processes likely to be altered in low-risk tumors. A higher TC was found to be inversely associated with more aggressive surrogate molecular subtypes and tumor characteristics (P < .05) including Ki-67 proliferation status (P < 5 × 10-07 ). Our low-risk TC-Gx, based on the weighted sum of 37 expression values of genes strongly correlated with TC, was associated with basal-like (P < 5 × 10-13 ), HER2-enriched subtype (P < 5 × 10-07 ) and worse 10-year breast cancer-specific survival (log-rank P < 5 × 10-04 ). Associations between low-risk TC-Gx and more aggressive molecular subtypes were replicated in an independent cohort from The Cancer Genome Atlas database (n = 975). Gene expression that correlated with low TC was enriched in proliferation and oncogenic signaling pathways (FDR < 0.05). Moreover, higher proliferation was a key factor explaining the association with worse survival. Women who developed breast cancer despite having a low risk were diagnosed with more aggressive tumors and had a worse prognosis, most likely driven by increased proliferation. Our findings imply the need to establish risk factors associated with more aggressive breast cancer subtypes.

Ecological quality assessement of marinas: An integrative approach combining biological and environmental data.

The importance of marinas as infrastructures for recreational boating is increasing substantially. However, information on their soft-bottom benthic communities, a key tool for managing programmes, is still scarce. We combined environment features with macro- and meiofaunal soft-bottom community information for assessing the ecological status of marinas with an integrative approach. To address this issue, we focused on eight marinas of the Southern Iberian Peninsula. Macro- and meiofauna data revealed high benthic heterogeneity at a spatial scale. The environmental variables which correlated best with macrofauna were mainly phosphorus, granulometry, and total organic carbon, and secondarily important variables were faecal coliforms, the biocide Irgarol, and heavy metals; total hydrocarbon concentration was also significant for meiofauna. Annelida was the dominant phylum in terms of number of species (37%) and abundance (66%) and were better descriptors of the environmental conditions than Arthropoda and Mollusca. Although identification to the species level is desirable and mandatory for assessing biological pollution, significant differences among marinas and correlations between fauna and abiotic variables were already detected at the level of family and order. This implies that biota assessment at higher levels may still be useful in monitoring programmes limited by time and budget constraints. The major novelty of this study lies in the development of an integrative assessment method based on the following selected ecological indicators: Marinas Environmental Pollution Index (MEPI), Biocontamination Index (BCI), macrofaunal biotic indices (AMBI, M-AMBI, BENTIX, MEDOCC and BENFES), macrofaunal taxa richness and Shannon-Wiener's diversity, and nematode:copepod index. This approach was able to discriminate marinas of the Southern Iberian Peninsula based on their ecological status, which ranged from poor to good. The method can be useful to design standards for assigning "sustainable quality seals" to those marinas with better values of ecological indicators.

Graph theory analysis of resting-state functional magnetic resonance imaging in essential tremor.

Essential tremor (ET) is a neurological disease with both motor and nonmotor manifestations; however, little is known about its underlying brain basis. Furthermore, the overall organization of the brain network in ET remains largely unexplored. We investigated the topological properties of brain functional network, derived from resting-state functional magnetic resonance imaging (MRI) data, in 23 ET patients versus 23 healthy controls. Graph theory analysis was used to assess the functional network organization. At the global level, the functional network of ET patients was characterized by lower small-worldness values than healthy controls-less clustered functionality of the brain. At the regional level, compared with the healthy controls, ET patients showed significantly higher values of global efficiency, cost and degree, and a shorter average path length in the left inferior frontal gyrus (pars opercularis), right inferior temporal gyrus (posterior division and temporo-occipital part), right inferior lateral occipital cortex, left paracingulate, bilateral precuneus bilaterally, left lingual gyrus, right hippocampus, left amygdala, nucleus accumbens bilaterally, and left middle temporal gyrus (posterior part). In addition, ET patients showed significant higher local efficiency and clustering coefficient values in frontal medial cortex bilaterally, subcallosal cortex, posterior cingulate cortex, parahippocampal gyri bilaterally (posterior division), right lingual gyrus, right cerebellar flocculus, right postcentral gyrus, right inferior semilunar lobule of cerebellum and culmen of vermis. Finally, the right intracalcarine cortex and the left orbitofrontal cortex showed a shorter average path length in ET patients, while the left frontal operculum and the right planum polare showed a higher betweenness centrality in ET patients. In conclusion, the efficiency of the overall brain functional network in ET is disrupted. Further, our results support the concept that ET is a disorder that disrupts widespread brain regions, including those outside of the brain regions responsible for tremor.

Methods for Simultaneous Robot-World-Hand-Eye Calibration: A Comparative Study.

In this paper, we propose two novel methods for robot-world-hand-eye calibration and provide a comparative analysis against six state-of-the-art methods. We examine the calibration problem from two alternative geometrical interpretations, called 'hand-eye' and 'robot-world-hand-eye', respectively. The study analyses the effects of specifying the objective function as pose error or reprojection error minimization problem. We provide three real and three simulated datasets with rendered images as part of the study. In addition, we propose a robotic arm error modeling approach to be used along with the simulated datasets for generating a realistic response. The tests on simulated data are performed in both ideal cases and with pseudo-realistic robotic arm pose and visual noise. Our methods show significant improvement and robustness on many metrics in various scenarios compared to state-of-the-art methods.

Risk and predictors of psoriasis in patients with breast cancer: a Swedish population-based cohort study.

BACKGROUND: The risk of psoriasis in patients with breast cancer is largely unknown, as available evidence is limited to case findings. We systematically examined the incidence and risk factors of psoriasis in patients with breast cancer. METHODS: A Swedish nationwide cohort of 56,235 breast cancer patients (2001-2012) was compared to 280,854 matched reference individuals from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. We also calculated HRs for psoriasis according to treatment, genetic, and lifestyle factors in a regional cohort of 8987 patients. RESULTS: In the nationwide cohort, 599 patients with breast cancer were diagnosed with psoriasis during a median follow-up of 5.1 years compared to 2795 cases in the matched reference individuals. This corresponded to an incidence rate of 1.9/1000 person-years in breast cancer patients vs. 1.7/1000 person-years in matched reference individuals. Breast cancer patients were at an increased risk of psoriasis (HR = 1.17; 95% confidence interval (CI) = 1.07-1.28), especially its most common subtype (psoriasis vulgaris; HR = 1.33; 95% CI = 1.17-1.52). The risk of psoriasis vulgaris was highest shortly after diagnosis but remained increased up to 12 years. Treatment-specific analyses indicated a higher risk of psoriasis in patients treated with radiotherapy (HR = 2.44; 95% CI = 1.44-4.12) and mastectomy (HR = 1.54, 95% CI = 1.03-2.31). Apart from treatment-specific effects, we identified genetic predisposition, obesity, and smoking as independent risk factors for psoriasis in breast cancer patients. CONCLUSIONS: The incidence of psoriasis is slightly elevated among patients with breast cancer, with treatment, lifestyle, and genetic factors defining the individual risk profile.

Unveiling a Technosol-based remediation approach for enhancing plant growth in an iron-rich acidic mine soil from the Rio Tinto Mars analog site.

This paper explores the potential of Technosols made from non-hazardous industrial wastes as a sustainable solution for highly acidic iron-rich soils at the Rio Tinto mining site (Spain), a terrestrial Mars analog. These mine soils exhibit extreme acidity (pHH2O = 2.1-3.0), low nutrient availability (non-acid cation saturation < 20 %), and high levels of Pb (3420 mg kg-1), Cu (504 mg kg-1), Zn (415 mg kg-1), and As (319 mg kg-1), hindering plant growth and ecosystem restoration. To address these challenges, the study systematically analyzed selected waste materials, formulated them into Technosols, and conducted a four-month pot trial to evaluate the growth of Brassica juncea under greenhouse conditions. Technosols were tailored by adding varying weight percentages of waste amendments into the mine Technosol, specifically 10 %, 25 %, and 50 %. The waste amendments comprised a blend of organic waste (water clarification sludge, WCS) and inorganic wastes (white steel slag, WSS; and furnace iron slag, FIS). The formulations included: (T0) exclusively mine Technosol (control); (T1) 60 % WCS + 40 % WSS; (T2) 60 % WCS + 40 % FIS; and (T3) 50 % WCS + 16.66 % WSS + 33.33 % FIS. The analyses covered leachate quality, soil pore water chemistry, and plant response (germination and survival rates, plant height, and leaf number). Results revealed a significant reduction in leachable contaminant concentrations, with Pb (26.16 mg kg-1), Zn (4.94 mg kg-1), and Cu (2.29 mg kg-1) dropping to negligible levels and shifting towards less toxic species. These changes improved soil conditions, promoting seed germination and seedling growth. Among the formulations tested, Technosol T1 showed promise in overcoming mine soil limitations, enhancing plant adaptation, buffering against acidification, and stabilizing contaminants through precipitation and adsorption mechanisms. The paper stresses the importance of tailoring waste amendments to specific soil conditions, and highlights the broader implications of the Technosol approach, such as waste valorization, soil stabilization, and insights for Brassica juncea growth in extreme environments, including Martian soil simulants.

Early Prostate Cancer Deaths Among Men With Higher vs Lower Genetic Risk.

Importance: Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility. Objective: To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts. Design, Setting, and Participants: This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019. Data were analyzed between April 2023 and April 2024. Exposures: Men were categorized according to modifiable lifestyle behaviors and genetic risk. A polygenic risk score above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as being at lower genetic risk. Main Outcomes and Measures: Prostate cancer death analyzed using time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age. Results: Among the 19 607 men included for analysis, the median (IQR) age at inclusion was 59.0 (53.0-64.7) years (MDCS) and 65.1 (58.0-71.8) years (HPFS). During follow-up, 107 early (by age 75 years) and 337 late (after age 75 years) prostate cancer deaths were observed. Compared with men at lower genetic risk, men at higher genetic risk had increased rates of both early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death, and higher lifetime risks of prostate cancer death (3.1% vs 1.3% [MDCS] and 2.3% vs 0.6% [HPFS]). Men at higher genetic risk accounted for 94 of 107 early prostate cancer deaths (88%), of which 36% (95% CI, 12%-60%) were estimated to be preventable through adherence to behaviors associated with a healthy lifestyle (not smoking, healthy weight, high physical activity, and a healthy diet). Conclusions and Relevance: In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.

Gastrointestinal symptoms and weight loss in cancer patients receiving chemotherapy.

Cancer patients receiving chemotherapy have a high risk of malnutrition secondary to the disease and treatment, and 40-80 % of cancer patients suffer from different degrees of malnutrition, depending on tumour subtype, location, staging and treatment strategy. Malnutrition in cancer patients affects the patient's overall condition, and it increases the number of complications, the adverse effects of chemotherapy and reduces the quality of life. The aim of the present study was to evaluate weight-loss prevalence depending on the tumour site and the gastrointestinal (GI) symptoms of oncology patients receiving chemotherapy. We included 191 cancer patients receiving chemotherapy. Files of all patients were reviewed to identify symptoms that might potentially influence weight loss. The nutritional status of all patients was also determined. The cancer sites in the patients were as follows: breast (31·9 %); non-colorectal GI (18·3 %); colorectal (10·4 %); lung (5·8 %); haematological (13·1 %); others (20·5 %). Of these patients, 58 % experienced some degree of weight loss, and its prevalence was higher among the non-colorectal GI and lung cancer patients. Common symptoms included nausea (59·6 %), anorexia (46 %) and constipation (31·9 %). A higher proportion of patients with ≥ 5 % weight loss experienced anorexia, nausea and vomiting (OR 9·5, 2·15 and 6·1, respectively). In conclusion, these results indicate that GI symptoms can influence weight loss in cancer patients, and they should be included in early nutritional evaluations.

Assessment of elemental composition in commercial fish of the Bay of Cádiz, Southern Iberian Peninsula.

The assessment of trace metal content in our fish diet is important due to the adverse effect on human health. Despite the increasing interest about the fish quality, little information is available for Southern Spain, a region characterized by high seafood intake. Nine species from the Bay of Cádiz with high commercial value were selected. Similar values were measured in the nine studied species for most of the elements, except for the macroelements Ca and S, and the microelements Fe, Mn and As, which showed significant differences among species. Metal Pollution Index (MPI) did not differ among species, and it was similar to those obtained for other Atlantic and Mediterranean locations. The values measured for the nine species were below the health limits provided by World, European and Spanish legislations, indicating that, in general terms, consumption of these species is safe in the study area.

Interval breast cancer is associated with interferon immune response.

BACKGROUND: The aggressive nature of breast cancers detected between planned mammographic screens, so-called interval cancers, remains elusive. Here, we aim to characterise underlying molecular features of interval cancer. METHODS: From 672 patients with invasive breast cancer, we analysed gene expression differences between 90 'true' interval cancer cases (i.e. women with low-dense breasts defined as per cent mammographic density <25%) and 310 screen-detected tumours while accounting for PAM50 subtypes and thus overall tumour aggressiveness. We computed an interval cancer gene expression profile (IC-Gx) in a total of 2270 breast tumours (regardless of interval cancer status) and tested for association with expression-based immune subtypes in breast cancer. In addition, we investigated the contribution of inherited and somatic genetic variants in distinct features of interval cancer. RESULTS: We identified 8331 genes nominally associated with interval cancer (P-value < 0.05, fold-change > 1.5). Gene set enrichment analysis showed immune-related pathways as key processes altered in interval cancer. Our IC-Gx, based on 47 genes with the strongest associations (false discovery rate < 0.05), was found to be associated mainly with immune subtypes involving interferon response. We isolated an interaction network of interval cancer and interferon genes for which a significant load of somatic and germline variants in class I interferon genes was observed. CONCLUSION: We identified novel molecular features of interval breast cancer highlighting interferon pathways as a potential target for prevention or treatment.

Ultrasound extraction optimization for bioactive molecules from Eucalyptus globulus leaves through antioxidant activity.

Antioxidant products present a very high added value and are demanded in the market. The optimization of their extraction is a high-stakes matter for both economic and environmental points of view. Ultrasound extraction has been considered one of the most promising methods, so the relative importance of key parameters may have decisive economic significance. For this reason, different parameters that have influence on the extraction capacity such as ultrasound power, time, temperature, pH and % ethanol in water have been studied to know the relationships between the independent parameters and their influence on the extraction from Eucalyptus globulus leaves. An experimental Box-Behnken factorial design and subsequent analysis by neural networks have been used. The relative influence of each parameter varies according to the nature of the extracted compound. In this regard, the higher capacity of extraction of the selected antioxidant compounds by means of the variation of the operation conditions can be facilitated. For all the studied compounds, temperature has been the most important parameter for their extraction. The relative content (%) of bioactive compounds (terpenes) in the optimized Eucalyptus globulus extract has been performed by GC-MS analysis.

Effects of Dietary Phenylalanine and Tyrosine Supplements on the Chronic Stress Response in the Seabream (Sparus aurata).

The increase of aquaculture production is associated with a growing interest in improving physiological status and welfare in fish. For this reason, the search for strategies for mitigating stress has been intensified, with one of these strategies being food supplementation with different amino acids (AA). The objective of this study was to evaluate the effects of dietary phenylalanine (Phe) and tyrosine (Tyr) supplements on the endocrine and physiological state of seabreams (Sparus aurata) subjected to chronic stress. The fish were stocked at 30 fish/tank in a recirculation aquatic system, fed one control diet and two diets supplemented with 5% Phe or Tyr for 90 days. Blood was drawn from 10 fish per tank every 30 days, and the weight and length were measured every 15 days. At the end of the experiment, length/weight of the fish were measured, and they were sacrificed for the extraction of blood, head kidney, liver, and brain. Classic plasma stress markers (glucose, lactate, proteins, and cortisol), as well as hormones derived from Phe and Tyr (adrenaline, norepinephrine, and dopamine) and the accumulation of AA were analyzed. Fish fed with diets supplemented with Phe or Tyr showed a reduction in various stress markers and physiological parameters. In addition, the stress condition favored a mobilization of AA toward the tissues, especially in supplemented diets, so this excess of AA could be used as an energy substrate to cope with stress.

Assessing environmental pollution levels in marinas.

Despite the growing interest in recreational boating and the increasing number of marinas along the world's coastlines, environmental knowledge of these ecosystems is still very scarce. Detailed data of pollutants in marinas are necessary to provide a global approach of environmental risks in the context of international management strategies. In the present study, a set of 64 variables (30 in seawater and 34 in sediments) were measured to compare marinas from the Southern Iberian Peninsula (SIP). Uni and multivariate analyses showed significant differences among marinas, evidencing the importance of management on a local scale. The most relevant variables determining these differences were turbidity and the biocide Irgarol 1051 in seawater, and granulometry, hydrocarbons and faecal coliforms in sediment. The use of normalization techniques with Al or Fe, and the suitability of different methodologies to measure Total Organic Matter in marinas were also discussed. Additionally, we perform a comprehensive literature review of worldwide marina stressors and develop a simple and straightforward method for assessing environmental quality. The method was tested using SIP marinas and was based on the comparison of 15 selected sediment stressors with background values, concentrations of worldwide sediment quality guidelines (SQGs), and reference conditions/security thresholds established by the programme of coastal waters in port areas (ROM 5.1). A global score was assigned using a new proposed index, Marinas Environmental Pollution Index (MEPI), ranging from 0 to 150 points according to the environmental quality (<90: bad, 90-120: moderate, >120: good). MEPI of marinas from SIP ranged from 60 to 110 points indicating bad or moderate levels of pollution. Environmental quality is one of the decisive factors for awarding eco-labels or eco-certifications, such as Blue Flags in marinas. Therefore, pollution baseline information and environmental tools are mandatory for correct assignation of these awards and necessary for assessing the efficiency of management actions.

Phenylalanine and Tyrosine as Feed Additives for Reducing Stress and Enhancing Welfare in Gilthead Seabream and Meagre.

Increased aquaculture production is associated with a growing interest in improving fish welfare. For this reason, the search for strategies to mitigate stress has intensified, one of these strategies being food supplementation with amino acids. The objective of this study was to evaluate the effects of dietary phenylalanine (Phe) and Tyrosine (Tyr) on the stress response and metabolism of juvenile gilthead seabreams (Sparus aurata) and meagres (Argyrosomus regius). Fish batches were fed a control diet and two diets supplemented with 5% Phe or Tyr for seven days. At the end of the experiment fish were stressed by air exposure for 3 min and then sacrificed for the extraction of blood and brain. Classical plasma stress markers were analyzed (glucose, lactate, proteins, cortisol), as well as hormones derived from those amino acids (adrenaline, noradrenaline and dopamine). Despite interspecific differences, fish fed the diets supplemented with Phe or Tyr showed a reduction on several stress markers. However, interspecific differences were detected for many indicators. Concretely, hormonal stress markers were significantly attenuated in meagres fed the enriched diets. Moreover, the stress condition favored a mobilization of amino acids towards the brain, especially in supplemented diets, hence this amino acid excess could be used as an energy substrate to cope with stress.

Características clínicas, bioquímicas y radiológicas en niñas con pubertad precoz central atendidas en un hospital público de Lima / Clinical, biochemical, and radiologic findings of girls with early puberty attended at a public hospital in Lima, Peru

RESUMEN Objetivo Describir las características clínicas, bioquímicas y radiológicas en niñas con pubertad precoz central (PPC) atendidas en un hospital público de Lima. Material y métodos Estudio tipo serie de casos. Se revisaron historias clínicas de niñas con diagnóstico de PPC. Se excluyeron niñas con pubertad precoz periférica (PPP), telarquia aislada y malformaciones. Se calculó el Z-IMC, Z-talla genética, Z-talla y proyección de talla final adulta (PFTA). Se utilizó t-Student, t-test, Wilcoxon y Shapiro-Wilk, mediante el software STATA versión 17. Se consideró estadísticamente significativo p<0,05. El estudio fue aprobado por el CIE de la UPCH y del HCH. Resultados: Se revisaron 86 historias. La edad media cronológica fue 8,16±1,09años y la edad media ósea fue 10,33±1,27años (p≤0,001) entre las medias de la edad ósea y la edad cronológica, el Z-talla de la niña y el Z-talla genética asimismo la PTFA y la talla genética (TG). Se encontró M2(19,7%), M3(59,3%) y M4(20,9%). Normopeso (27,9%), sobrepeso (30,2%) y obesidad (41,8%). La mediana de LH fue 0,6 (RIQ:0,4-1,8) y FSH fue 3,4 (RIQ:2,1-5,2) Conclusión La edad cronológica al diagnóstico fue tardía con una edad ósea significativamente mayor respecto a la cronológica. La talla de la niña respecto a su TG fue significativamente mayor. La PTFA fue significativamente menor que la TG. La mayoría presentó desarrollo mamario avanzado, sobrepeso y obesidad.

SUMMARY Objective To describe the clinical, biochemical, and radiologic findings of girls with early puberty (EP) attended at a public hospital in Lima, Peru. Methods This is a case series study that results from the review of clinical charts of girls diagnosed of (EP). Patients with peripheral EP, isolated thelarche and malformations were excluded. The Z-IMC, Z-genetic height, Z-height, and projected adult final height (PAFH) were calculated. The t-Student, Wilcoxon and Shapiro-Wilk tests were calculated using STATA version 17, a p values < 0.05 was considered statistically significant, the study was approved by the IRB of UPCH and HCH. Results We reviewed 86 charts; mean age was 8,16±1.09 years and mean bone age was 10.33±1.27 years (p≤0.001). We found M2(19.7%), M3(59.3%) and M4(20.9%). Normal weight (27.9%), overweight (30.2%) and obesity (41.8%). Median LH was 0.6 (RIQ:0.4-1.8) and median FSH was 3.4 (RIQ:2.1-5.2). Conclusion Chronologic age at diagnosis was late with a bone age higher than chronologic age. Height of girls compared to genetic height was higher. PAFH was lower than genetic height. Most of the girls presented with advanced breast development, overweight and obesity.

Differential Burden of Rare and Common Variants on Tumor Characteristics, Survival, and Mode of Detection in Breast Cancer.

Genetic variants that increase breast cancer risk can be rare or common. This study tests whether the genetic risk stratification of breast cancer by rare and common variants in established loci can discriminate tumors with different biology, patient survival, and mode of detection. Multinomial logistic regression tested associations between genetic risk load [protein-truncating variant (PTV) carriership in 31 breast cancer predisposition genes-or polygenic risk score (PRS) using 162 single-nucleotide polymorphisms], tumor characteristics, and mode of detection (OR). Ten-year breast cancer-specific survival (HR) was estimated using Cox regression models. In this unselected cohort of 5,099 patients with breast cancer diagnosed in Sweden between 2001 and 2008, PTV carriers (n = 597) were younger and associated with more aggressive tumor phenotypes (ER-negative, large size, high grade, high proliferation, luminal B, and basal-like subtype) and worse outcome (HR, 1.65; 1.16-2.36) than noncarriers. After excluding 92 BRCA1/2 carriers, PTV carriership remained associated with high grade and worse survival (HR, 1.76; 1.21-2.56). In 5,007 BRCA1/2 noncarriers, higher PRS was associated with less aggressive tumor characteristics (ER-positive, PR-positive, small size, low grade, low proliferation, and luminal A subtype). Among patients with low mammographic density (<25%), non-BRCA1/2 PTV carriers were more often interval than screen-detected breast cancer (OR, 1.89; 1.12-3.21) than noncarriers. In contrast, higher PRS was associated with lower risk of interval compared with screen-detected cancer (OR, 0.77; 0.64-0.93) in women with low mammographic density. These findings suggest that rare and common breast cancer susceptibility loci are differentially associated with tumor characteristics, survival, and mode of detection.Significance: These findings offer the potential to improve screening practices for breast cancer by providing a deeper understanding of how risk variants affect disease progression and mode of detection. Cancer Res; 78(21); 6329-38. ©2018 AACR.

Common shared genetic variation behind decreased risk of breast cancer in celiac disease.

There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = -0.17, s.e. 0.05, P < 0.001) and overlap (P permuted < 0.001) between celiac disease and breast cancer. Using individual-level genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (P CD < 1.00E-05, P BC ≤ 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.

Arsenic speciation in river and estuarine waters from southwest Spain.

An arsenic speciation survey was carried out in water samples from the Tinto and Odiel Rivers (southwest of Spain), as well as their common estuary. Both rivers are affected by acid mine drainage (AMD) and represent an input of heavy metals into the estuary, which also suffers from industrial water discharges. Samples were taken in December 2000 and July 2001. The arsenic species considered were arsenite (As(III)), arsenate (As(V)), monomethylarsonic (MMA) and dimethylarsinic (DMA) ions using coupled high-performance liquid chromatography-hydride generation-inductively coupled plasma-mass spectrometry (HPLC-HG-ICP-MS) for their determination. Parameters such as pH, salinity, redox potential and dissolved O2 were also measured. The results revealed that the acid mine drainage originating mainly during winter along the upper part of the Tinto River course causes high inorganic concentrations of dissolved arsenic, up to 600 microg l(-1) of As(III) and 200 microg l(-1) of As(V). In summer, As(III) levels decreased due to the diminution of the input from acid mine drainage and also because of oxidation, with a corresponding increase of As(V) level. Furthermore, the extreme acidic conditions of this river (pH 2.3-2-6) do not allow biological activity sufficient to produce significant concentrations of methylated arsenic species. The arsenic concentrations in the nearby Odiel River were always 5-10 times lower than in the Tinto River, with arsenic levels usually below 100 microg l(-1), dominated by As(V), indicating that it is less affected by acid mine drainage. The highest inorganic arsenic species concentrations were found where the river crosses a mining site, which corresponds to the highest As(III) values. Significant biological activity in this river produced methylated species that were detected along the water-course, with the highest concentrations at the lower course of the river, accounting for up to 53-61% of the total dissolved arsenic. At the common estuary formed by both rivers, only arsenate was detected in most samples at lower concentrations than in the riverine water samples. The tidal cycle showed a similar pattern of dilution of the arsenate when seawater comes into the estuary. Methylated species were not found either in summer or winter, at least at the 0.1 microg l(-1) level, possibly because of the high turbidity of the waters, producing an inhibition of the phytoplankton activity. In addition to the riverine inputs into the common estuary, industrial activity also represents an important source of arsenic as the discharge from a Cu smelter produced the highest arsenate level of all samples in estuary and also the only sample with significant arsenite concentration. Furthermore, the underlying iron-oxide-rich sediments represent an importance source of arsenic into the water column. In three nearby estuaries not affected by industrial activity or acid mine drainage, arsenic levels remained below detection limits.