Frascos de cristal, plátanos y moscas: género, emociones y prácticas de la genética de Drosophila / Glass jars, bananas, and flies gender, emotions, and practices of Drosophila genetics

Los plátanos y los tarros de cristal fueron y son componentes de la cultura material de la genética de Drosophila, como lo fueron y son también las moscas que crecían en su interior. Estos objetos son objetos híbridos —materiales, sensoriales y emocionales—, que circularon entre el campo y el laboratorio, entre las aulas, puestos de investigación y cocinas de las casas de quienes se dedicaron a los estudios de la herencia y la evolución. Circularon también a través del tiempo y del espacio geográfico al formar parte del conocimiento colectivo de la comunidad de genetistas de Drosophila, de sus recuerdos y de los de sus hijas e hijos. A través de la combinación de fuentes escritas, académicas e institucionales y de otras que son orales, subjetivas y emocionales, cobran vida y con ellos las actividades y prácticas de quienes los utilizaban, casi siempre mujeres. Al evocarlos, aparecen también normas como las de género, que rodeaban a las personas en el momento de la experiencia y juicios de valor que elaboraron, y se elaboraron, sobre los objetos, sus usos y las identidades de quienes los emplearon. Este artículo pretende así, estudiando prácticas y objetos de una disciplina como la genética de Drosophila, contribuir a la construcción de una historia de la genética más inclusiva, a la historia de las mujeres científicas y a los estudios sobre el papel de las emociones, el cuerpo y la memoria en la construcción de conocimiento histórico y científico. (AU)

Bananas and glass jars were and are components of the material culture of Drosophila genetics. These hybrid (material, sensory and emotional) objects circulated between the field and the laboratory and among the classrooms, research stations, and kitchens of those who dedicated themselves to studies of heredity and evolution. They also circulated through time and geographic space as they became part of the collective knowledge of the community of Drosophila geneticists and the memories of their daughters and sons. The combination of written, objective, conceptual and, above all, oral, subjective and emotional sources brings them to life along with the activities and practices of those who used them, almost always women; they have not been erased from these emotional records as they have been from institutional records. Norms also appear, such as gender norms, which surrounded people at the time of the experience and influenced their value judgments about the objects, practices and identities of those who carried them out. Thus, by studying the practices and objects of a discipline such as Drosophila genetics, this article aims to contribute to the construction of a more inclusive history of genetics, to the history of women scientists and to studies on the role of emotions, the body, and memory in the construction of historical knowledge. (AU)

Pro- and anti-inflammatory response in neurological disorders associated to anti-glutamate decarboxylase antibodies.

Rare conditions showing psychiatric symptoms and movement disorders have been linked with the presence of anti-glutamate decarboxylase antibodies. Proinflammatory and antiinflammatory immune responses were assessed in patients with neurological disorders associated to anti-glutamic acid decarboxylase antibodies (NDGAD). Immunoregulatory and proinflammatory cell populations were quantified by flow cytometry. No polarization toward Th1, Th2, or Th17 phenotypes was observed in NDGAD patients. Immunoregulatory responses were significantly reduced for Breg, activated Treg, Tr1, and Th3 cells, suggesting a deficient regulatory response, while intermediate monocyte levels were increased. The reduced levels of regulatory T and B cells suggest an impairment in regulatory immune response, while intermediate monocytes could be playing a role in the increased proinflammatory response.

Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4 double-knockout mice, GM3 ganglioside is stored in microglia, vascular pericytes, and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of lipofuscin bodies, and memory loss, whereas their cortical and hippocampal neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have reduced levels of GM1 ganglioside and myelin in neuronal axons. Furthermore, neuraminidase 3 deficiency drastically increased storage of GM2 in the brain tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human gangliosidosis, indicating that this enzyme is responsible for the metabolic bypass of ß-hexosaminidase A deficiency. Together, our results provide the first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS function by catabolizing gangliosides and preventing their storage in lipofuscin bodies.-Pan, X., De Britto Pará De Aragão, C., Velasco-Martin, J. P., Priestman, D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt, F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

Altered mitochondrial function, capacitative calcium entry and contractions in the aorta of hypertensive rats.

OBJECTIVE: It has been suggested that Ca entry through store-operated Ca channels (SOCs) is regulated by a dynamic interplay between the endoplasmic reticulum Ca stores and the mitochondria. These relationships drive the activation and inactivation of SOCs, yet it remains unclear whether this regulation of SOCs by mitochondria is altered in the aorta of spontaneously hypertensive rats (SHRs). METHODS: We performed a thorough study of the mitochondrial membrane potential, the ability of mitochondria to deal with cytosolic Ca, capacitative Ca entry (CCE), and stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (orai1) protein expression, as well as the contractile capacity of aortic rings, in normotensive Wistar Kyoto rats (WKYs) and SHRs. RESULTS: Changes were observed in aortic tissue and cultured vascular smooth muscle cells isolated from SHRs relative to WKYs, including more depolarized mitochondria, stronger CCE upon the addition of Ca, larger cytosolic Ca transients (cytosolic Ca concentration) or aortic ring contraction elicited by endoplasmic reticulum depletion and a significant increase in STIM1 protein expression but not of orai1. CONCLUSION: These results suggest that the impaired Ca buffering capacity of partially depolarized mitochondria dysregulates CCE, leading to overfilling of the endoplasmic reticulum Ca store through enhanced STIM1/orai1 interactions and an increase in aorta contractions in SHRs. Thus, understanding the implications of the alterations to STIM1/orai1, and their relationship to mitochondria, may aid drug development and therapeutic strategies to treat hypertension, as well as its long-term sequelae in poorly controlled patients.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile.

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30-65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile.

Neoadjuvant Systemic Therapy in Breast Cancer: Association of Contrast-enhanced MR Imaging Findings, Diffusion-weighted Imaging Findings, and Tumor Subtype with Tumor Response.

Purpose To investigate the performance of tumor subtype and various magnetic resonance (MR) imaging parameters in the assessment of tumor response to neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline a model of pathologic response, considering pathologic complete response (pCR) as the complete absence of any residual invasive cancer or ductal carcinoma in situ (DCIS). Materials and Methods This was an institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From November 2009 to December 2014, 111 patients with histopathologically confirmed invasive breast cancer who were undergoing NST were included (mean age, 54 years; range, 27-84 years). Breast MR imaging was performed before and after treatment. Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs) were obtained by using two different methods. ADC ratio (mean posttreatment ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any residual invasive cancer or DCIS. Multivariate regression analysis and receiver operating characteristic analysis were performed. Results According to their immunohistochemical (IHC) profile, tumors were classified as human epidermal growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER) positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive subtypes. Absence of late enhancement at posttreatment MR imaging was significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC ratio significantly increased when pCR was achieved (P < .001). A κ value of 0.479 was found for late enhancement (P < .001), and the intraclass correlation coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with the single-value method and those obtained with the mean-value methods was observed. The model combining the IHC subtype, ADC ratio, and late enhancement had the highest association with pathologic response, achieving an AUC of 0.92 (95% confidence interval: 0.86, 0.97). Conclusion Triple-negative or HER2-positive tumors showing absence of late enhancement and high ADC ratio after NST are associated with pCR. © RSNA, 2016 Online supplemental material is available for this article.

Liver Growth Factor (LGF) Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich's Ataxia Transgenic Mice.

Friedreich's ataxia (FA) is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF), which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXN)YG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 µg/mouse) exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold) and heart (1.2-fold). LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.

Thyroid hormones inhibit TGF-ß signaling and attenuate fibrotic responses.

TGF-ß, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-ß/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD-binding elements in response to TGF-ß, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.

Autoregulatory loop of nuclear corepressor 1 expression controls invasion, tumor growth, and metastasis.

Nuclear corepressor 1 (NCoR) associates with nuclear receptors and other transcription factors leading to transcriptional repression. We show here that NCoR depletion enhances cancer cell invasion and increases tumor growth and metastatic potential in nude mice. These changes are related to repressed transcription of genes associated with increased metastasis and poor prognosis in patients. Strikingly, transient NCoR silencing leads to heterochromatinization and stable silencing of the NCoR gene, suggesting that NCoR loss can be propagated, contributing to tumor progression even in the absence of NCoR gene mutations. Down-regulation of the thyroid hormone receptor ß1 (TRß) appears to be associated with cancer onset and progression. We found that expression of TRß increases NCoR levels and that this induction is essential in mediating inhibition of tumor growth and metastasis by this receptor. Moreover, NCoR is down-regulated in human hepatocarcinomas and in the more aggressive breast cancer tumors, and its expression correlates positively with that of TRß. These data provide a molecular basis for the anticancer actions of this corepressor and identify NCoR as a potential molecular target for development of novel cancer therapies.

Amyloidosis of the Breast: Three Different and Unusual Presentations of a Rare Entity.

BACKGROUND: Amyloidosis involving the breast is a rare finding and it may present as a solitary mass called 'amyloid tumor'. According to the largest case series, the amyloid deposits are usually of the AL type (commonly x03BA; light chain). METHODS: We report 3 cases diagnosed at our institution in the period from 2000 to 2015. Radiological, histological and immunohistochemical studies were performed. RESULTS AND CONCLUSIONS: Together with a case presenting in a patient with multiple myeloma, we describe 2 unique presentations including 1 associated with CREST syndrome in a patient with a previous history of breast carcinoma and another, also associated with cancer, with transthyretin deposits in a woman with a TTR gene mutation and a family history of familial amyloidotic polyneuropathy. These cases are an example of the vast heterogeneity of this disorder regarding its clinical presentation, the type of amyloid deposits and other diseases associated with breast amyloidosis.

WNT-3A regulates an Axin1/NRF2 complex that regulates antioxidant metabolism in hepatocytes.

AIMS: Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a master regulator of oxidant and xenobiotic metabolism, but it is unknown how it is regulated to provide basal expression of this defense system. Here, we studied the putative connection between NRF2 and the canonical WNT pathway, which modulates hepatocyte metabolism. RESULTS: WNT-3A increased the levels of NRF2 and its transcriptional signature in mouse hepatocytes and HEK293T cells. The use of short interfering RNAs in hepatocytes and mouse embryonic fibroblasts which are deficient in the redox sensor Kelch-like ECH-associated protein 1 (KEAP1) indicated that WNT-3A activates NRF2 in a ß-Catenin- and KEAP1-independent manner. WNT-3A stabilized NRF2 by preventing its GSK-3-dependent phosphorylation and subsequent SCF/ß-TrCP-dependent ubiquitination and proteasomal degradation. Axin1 and NRF2 were physically associated in a protein complex that was regulated by WNT-3A, involving the central region of Axin1 and the Neh4/Neh5 domains of NRF2. Axin1 knockdown increased NRF2 protein levels, while Axin1 stabilization with Tankyrase inhibitors blocked WNT/NRF2 signaling. The relevance of this novel pathway was assessed in mice with a conditional deletion of Axin1 in the liver, which showed upregulation of the NRF2 signature in hepatocytes and disruption of liver zonation of antioxidant metabolism. INNOVATION: NRF2 takes part in a protein complex with Axin1 that is regulated by the canonical WNT pathway. This new WNT-NRF2 axis controls the antioxidant metabolism of hepatocytes. CONCLUSION: These results uncover the participation of NRF2 in a WNT-regulated signalosome that participates in basal maintenance of hepatic antioxidant metabolism.

Single reading with computer-aided detection performed by selected radiologists in a breast cancer screening program.

OBJECTIVES: To assess the impact of shifting from a standard double reading plus arbitration protocol to a single reading by experienced radiologists assisted by computer-aided detection (CAD) in a breast cancer screening program. METHODS: This was a prospective study approved by the ethics committee. Data from 21,321 consecutive screening mammograms in incident rounds (2010-2012) were read following a single reading plus CAD protocol and compared with data from 47,462 consecutive screening mammograms in incident rounds (2004-2010) that were interpreted following a double reading plus arbitration protocol. For the single reading, radiologists were selected on the basis of the appraisement of their previous performance. RESULTS: Period 2010-2012 vs. period 2004-2010: Cancer detection rate (CDR): 6.1‰ (95% confidence interval: 5.1-7.2) vs. 5.25‰; Recall rate (RR): 7.02% (95% confidence interval: 6.7-7.4) vs. 7.24% (selected readers before arbitration) and vs. 3.94 (all readers after arbitration); Predictive positive value of recall: 8.69% vs. 13.32%. Average size of invasive cancers: 14.6±9.5mm vs. 14.3±9.5mm. Stage: 0 (22.3/26.1%); I (59.2/50.8%); II (19.2/17.1%); III (3.1/3.3%); IV (0/1.9%). Specialized breast radiologists performed better than general radiologists. CONCLUSIONS: The cancer detection rate of the screening program improved using a single reading protocol by experienced radiologists assisted by CAD, at the cost of a moderate increase of the recall rate mainly related to the lack of arbitration.

NOD1 receptor is up-regulated in diabetic human and murine myocardium.

Type 2 diabetes has a complex pathology that involves a chronic inflammatory state. Emerging evidence suggests a link between the innate immune system receptor NOD1 (nucleotide-binding and oligomerization domain 1) and the pathogenesis of diabetes, in monocytes and hepatic and adipose tissues. The aim of the present study was to assess the role of NOD1 in the progression of diabetic cardiomyopathy. We have measured NOD1 protein in cardiac tissue from Type 2 diabetic (db) mice. Heart and isolated cardiomyocytes from db mice revealed a significant increase in NOD1, together with an up-regulation of nuclear factor κB (NF-κB) and increased apoptosis. Heart tissue also exhibited an enhanced expression of pro-inflammatory cytokines. Selective NOD1 activation with C12-γ-D-glutamyl-m-diaminopimelic acid (iEDAP) resulted in an increased NF-κB activation and apoptosis, demonstrating the involvement of NOD1 both in wild-type and db mice. Moreover, HL-1 cardiomyocytes exposed to elevated concentrations of glucose plus palmitate displayed an enhanced NF-κB activity and apoptotic profile, which was prevented by silencing of NOD1 expression. To address this issue in human pathology, NOD1 expression was evaluated in myocardium obtained from patients with Type 2 diabetes (T2DMH) and from normoglycaemic individuals without cardiovascular histories (NH). We have found that NOD1 was expressed in both NH and T2DMH; however, NOD1 expression was significantly pronounced in T2DMH. Furthermore, both the pro-inflammatory cytokine tumour necrosis factor α (TNF-α) and the apoptosis mediator caspase-3 were up-regulated in T2DMH samples. Taken together, our results define an active role for NOD1 in the heightened inflammatory environment associated with both experimental and human diabetic cardiac disease.

Efecto de la maca peruana (lepidium meyenii) y de la melatonina sobre el desarrollo testicular del ratón expuesto a hipoxia hipobárica continua / Effect of peruvian maca (lepidium meyenii) and melatonin on testicular development of mice exposed to continuous hypobaric hypoxia

El estudio de la hipoxia hipobárica (HH) determina un problema de salud pública y laboral en poblaciones que habitan en zonas de altura. La disminución del oxígeno afecta a diferentes órganos, incluyendo el testículo. El organismo responde frente a la hipoxia estimulando la angiogénesis, el flujo sanguíneo testicular e incrementa la temperatura intraescrotal, lo cual produce un daño de la espermatogénesis. Nuestro estudio valoró el efecto que produce la HH sobre el testículo del ratón. Se utilizó una cámara hipobárica regulada a 4.200 metros sobre el nivel del mar (msnm), en periodos de hipoxia durante 8,3; 16,6 y 24,9 días, en comparación a un grupo control en normoxia (500 msnm). En estos tres grupos, a unos ratones se administró melatonina, a otros maca (Lepidium meyenii) y a otros la combinación de melatonina y maca. Los objetivos fueron evaluar si la ingesta de maca protege al testículo, reduciendo el daño generado por la hipoxia, y determinar un posible efecto sinérgico de la melatonina y de la maca. La exposición a HH continua produjo una disminución del diámetro de los túbulos seminíferos y del lumen tubular; además, el seminograma demostró una reducción del recuento espermático, un aumento de la teratozoospermia y una reducción de la calidad del ADN espermático. La administración de maca aislada o la combinación de maca y melatonina en animales sometidos a HH produjo una notable mejoría de los parámetros relacionados con la función de los espermatozoides, siendo significativos la disminución del número de espermatozoides con morfología anormal y de la compactación del DNA, alcanzando en algunos casos valores próximos a los de los animales normóxicos. Los datos del presente modelo de HH corroboran los excelentes beneficios que la ingesta de maca tiene sobre la capacidad reproductiva de poblaciones que viven en áreas geográficas de grandes alturas.

Hypobaric hypoxia (HH) is a decisive factor in human health in populations that reside at high altitude levels. Low oxygen rate affects most tissues and organs, including the testis. In humans, hypoxia stimulates angiogenesis, testicular blood flow and increases intrascrotal temperature which determines negative effects on sperm production. Our study researched the effects of HH in mice testicle. Mice were housed in a hypobaric chamber with a setting at 4,200 m above sea level during three different periods of hypoxia (8.3, 16.6 and 24.9 days). Control groups were housed at normoxic conditions (500 m above sea level). Hypoxic mice were treated with melatonin, maca plant (Lepidium meyenii) and melatonin and maca combination. The aim of present study was to determine if maca consumption protects testis against harmful effects of hypoxia and to determine a possible synergistic effect between melatonin and maca administration. In this article we have demonstrated that hypoxia produces a considerable decrease of seminiferous tubules diameter and lumen diameter. Moreover, seminogram showed a reduced sperm count, increased teratozoospermia and a reduction of DNA quality. The HH mice treatment with maca or maca-melatonin combination showed statistically significant improvement at sperm function parameters, and in the reduction of sperm morphology abnormalities and DNA compaction, in some cases attaining rates closer to those registered in normoxic mice. Our experimental data corroborates that maca consumption improves reproductive capacity of populations that inhabit high altitude regions.

Dynamic contrast-enhanced MRI reveals the extent and the microvascular pattern of breast ductal carcinoma in situ.

To report the role of magnetic resonance imaging (MRI) in assessing the extent of breast ductal carcinoma in situ (DCIS). To assess whether the microvascularity pattern in DCIS correlates with magnetic resonance enhancement. Eighty-five histologically proven DCIS (77 pure DCIS, eight microinvasive DCIS) were prospectively studied with MRI. The morphology of magnetic resonance enhancement and the kinetic curve was recorded. Histopathologically, intraductal lesions were classified according to Van Nuys score. Tumor microvascularity was immunohistochemically assessed in a subset of 24 DCIS evaluating the number of microvessels, microvascularity area, and microvascularity pattern (diffuse or periductal). On the mammogram, 74% of DCIS appeared as microcalcifications. On MRI, 70% of DCIS showed enhancement. Non-mass-like uptake was observed in 78% of cases. The mean size of nonenhancing carcinomas was significantly lower than that of enhancing carcinomas (p = 0.033). The diffuse pattern was more frequent than the periductal pattern. A significant relationship between the morphology of MR enhancement and the microvascularity pattern was observed (p = 0.036); thus, 90% of DCIS showing segmental enhancement on MRI displayed a diffuse pattern while all DCIS with ductal enhancement showed a periductal pattern. There was a significant relationship between the maximum area of microvascularity and the vascular pattern (p = 0.015); periductal patterns showed larger areas than diffuse patterns. The lesion size was significantly larger as the Van Nuys score increased (p < 0.001) and was also related to the number of microvessels (p = 0.012). The mean area of microvascularity of DCIS was significantly larger as the Van Nuys score increased (p = 0.02). Breast MRI helps depict the extent of DCIS and reveals its microvascular pattern.

Sterile inflammation in acetaminophen-induced liver injury is mediated by Cot/tpl2.

Cot/tpl2 (MAP3K8) activates MKK1/2-Erk1/2 following stimulation of the Toll-like/IL-1 receptor superfamily. Here, we investigated the role of Cot/tpl2 in sterile inflammation and drug-induced liver toxicity. Cot/tpl2 KO mice exhibited reduced hepatic injury after acetaminophen challenge, as evidenced by decreased serum levels of both alanine and aspartate aminotransferases, decreased hepatic necrosis, and increased survival relative to Wt mice. Serum levels of both alanine and aspartate aminotransferases were also lower after intraperitoneal injection of acetaminophen in mice expressing an inactive form of Cot/tpl2 compared with Wt mice, suggesting that Cot/tpl2 activity contributes to acetaminophen-induced liver injury. Furthermore, Cot/tpl2 deficiency reduced neutrophil and macrophage infiltration in the liver of mice treated with acetaminophen, as well as their hepatic and systemic levels of IL-1α. Intraperitoneal injection of damage-associated molecular patterns from necrotic hepatocytes also impaired the recruitment of leukocytes and decreased the levels of several cytokines in the peritoneal cavity in Cot/tpl2 KO mice compared with Wt counterparts. Moreover, similar activation profiles of intracellular pathways were observed in Wt macrophages stimulated with Wt or Cot/tpl2 KO damage-associated molecular patterns. However, upon stimulation with damage-associated molecular patterns, the activation of Erk1/2 and JNK was deficient in Cot/tpl2 KO macrophages compared with their Wt counterparts; an effect accompanied by weaker release of several cytokines, including IL-1α, an important component in the development of sterile inflammation. Taken together, these findings indicate that Cot/tpl2 contributes to acetaminophen-induced liver injury, providing some insight into the underlying molecular mechanisms.

Role of computer-aided detection in very small screening detected invasive breast cancers.

This study aims to assess computer-aided detection (CAD) performance with full-field digital mammography (FFDM) in very small (equal to or less than 1 cm) invasive breast cancers. Sixty-eight invasive breast cancers less than or equal to 1 cm were retrospectively studied. All cases were detected with FFDM in women aged 49-69 years from our breast cancer screening program. Radiological characteristics of lesions following BI-RADS descriptors were recorded and compared with CAD sensitivity. Age, size, BI-RADS classification, breast density type, histological type of the neoplasm, and role of the CAD were also assessed. Per-study specificity and mass false-positive rate were determined by using 100 normal consecutive studies. Thirty-seven (54.4 %) masses, 17 (25 %) calcifications, 6 (8.8 %) masses with calcifications, 7 (10.3 %) architectural distortions, and 1 asymmetry (1.5 %) were found. CAD showed an overall sensitivity of 86.7 % (masses, 86.5 %; calcifications, 100 %; masses with calcifications, 100 %; and architectural distortion, 57.14 %), CAD failed to detect 9 out of 68 cases: 5 of 37 masses, 3 of 7 architectural distortions, and 1 of 1 asymmetry. Fifteen out of 37 masses were hyperdense, and all of them were detected by CAD. No association was seen among mass morphology or margins and detectability. Per-study specificity and CAD false-positive rate was 26 % and 1.76 false marks per study. In conclusion, CAD shows a high sensitivity and a low specificity. Lesion size, histology, and breast density do not influence sensitivity. Mammographic features, mass density, and thickness of the spicules in architectural distortions do influence.

Mammographic features of screening detected pT1 (a-b) invasive breast cancer using BI-RADS lexicon.

AIM: To describe mammographic features in screening detected invasive breast cancer less than or equal to 10mm using Breast Imaging Reporting and Data System lexicon in full-field digital mammography. PATIENTS AND METHODS: A retrospective analysis of 123 pT1 (a-b) invasive breast cancers in women aged 50-69 years from our screening program. Radiologic patterns were: masses, calcifications, distortions, asymmetries and mixed. Masses: shape, margins and density, and calcifications: morphology, number of flecks and size of the cluster were taken into account, following Breast Imaging Reporting and Data System terminology. RESULTS: We found 61 masses (49.6%), 8 masses with calcifications (6.5%), 30 groups of calcifications (24.4%), 19 architectural distortions (15.4%), 1 architectural distortion with calcifications (0.8%), 4 asymmetries (3.2%). Sixty out of 69 masses were irregular in shape, 6 lobular, 2 ovals and 1 round. Thirty-four showed ill-defined margins, 29 spiculated and 6 microlobulated. Most of them showed a density similar to surrounding fibroglandular tissue. Calcifications were pleomorphic or fine linear in 24 of 30 (80%). Most of cases showed more than 10 flecks and a size greater than 1cm. CONCLUSION: The predominant radiologic finding is an irregular, isodense mass those margins tend to share different descriptors, being ill-defined margins the most constant finding. Calcifications representing invasive cancer are predominantly pleomorphic with more than 10 flecks per cm. Architectural distortion and invasive tubular carcinoma are more common than reported in general series.

Selecting the best anthropometric variables to characterize a population of healthy elderly persons.

The objective is to select the best anthropometric measurements to characterize a healthy elderly population. For that, 1030 healthy elderly persons (508 men and 522 women) living independently or in an institution (in both public and private homes) were enrolled for this population-based, cross-sectional study conducted from February 2004 to May 2005. Anthropometric measurements were made by the same investigator according to standard techniques of the WHO. Across several age groups, men were significantly heavier and taller than women whereas skinfold thicknesses were significantly greater in women than men. Through statistical analysis we were able to identify the variables providing most information and that could also best discriminate between sex, age and independent versus institutionalized persons: height, weight, one of the skinfold thickness measurements and mid-upper arm circumference. The number of age groups in both the male and female populations could be limited to three.

Selecting the best anthropometric variables to characterize a population of healthy elderly persons / Selección de las variables antropométricas más adecuadas para caracterizar una población de personas mayores sanas

The objective is to select the best anthropometric measurements to characterize a healthy elderly population. For that, 1030 healthy elderly persons (508 men and 522 women) living independently or in an institution (in both public and private homes) were enrolled for this population-based, cross-sectional study conducted from February 2004 to May 2005. Anthropometric measurements were made by the same investigator according to standard techniques of the WHO. Across several age groups, men were significantly heavier and taller than women whereas skinfold thicknesses were significantly greater in women than men. Through statistical analysis we were able to identify the variables providing most information and that could also best discriminate between sex, age and independent versus institutionalized persons: height, weight, one of the skinfold thickness measurements and mid-upper arm circumference. The number of age groups in both the male and female populations could be limited to three (AU)

El objetivo es la selección de las variables antropométricas más adecuadas para caracterizar poblaciones sanas de personas mayores. Para ello se han seleccionado aleatoriamente 1030 de estas personas (508 hombres y 522 mujeres) institucionalizados en residencias públicas, privadas y no institucionalizados. Todas las medidas antropométricas se realizaron por parte del mismo investigador de acuerdo con las técnicas estandarizadas por la OMS. En todos los grupos de edad se ha encontrado que los hombres son significativamente más altos y tienen un peso mayor que las mujeres, al contrario que ocurre con los distintos pliegues. Mediante el análisis estadístico de los datos hemos podido identificar las variables que proporcionan mayor información y que además permiten diferenciar los sujetos por sexo, edad y lugar de residencia: peso, altura, uno de los pliegues y la circunferencia muscular del brazo. En cuanto a los segmentos de edad, pueden reducirse a tres (AU)