Fixated and Not Fixated Regions of Mammograms: A Higher-Order Statistical Analysis of Visual Search Behavior

Publication date: Available online 27 January 2017
Source:Academic Radiology
Author(s): Suneeta Mall, Patrick Brennan, Claudia Mello-Thoms
Rationale and ObjectivesVisual search is an inhomogeneous yet efficient sampling process accomplished by the saccades and the central (foveal) vision. Areas that attract the central vision have been studied for errors in interpretation of medical imaging. In this study, we extend existing visual search studies to understand what characterizes areas that receive direct visual attention and elicit a mark by the radiologist (True and False Positive decisions) from those that elicit a mark but were captured by the peripheral vision. We also investigate if there are any differences between these areas and those that are never fixated by radiologists.Materials and MethodsEight radiologists participated in this fully crossed multi-reader multi-case visual search study of digital mammography (DM) involving 120 two-view cases (59 cancers). From these DM images, 3 types of areas, namely Fixated Clusters (FC), Marked Peripherally Fixated Clusters (MPFC) and Never Fixated Clusters (NFC), were extracted and analysed using statistical information theory (in the form of third and fourth-order cumulants and polyspectrum [specifically bispectrum and trispectrum]) in addition to traditional second-order statistics (in the form of power spectrum) and other nonspectral features to characterize these types of areas.ResultsOur results suggest that energy profiles of FC, MPFC, and NFC areas are distinct. We found evidence that energy profiles and dwell time of these areas influence radiologists' decisions (and confidence in such decisions). We also noted that foveated areas are selected on the basis of being most informative.ConclusionWe show that properties of these areas influence radiologists' decisions and their confidence in the decisions made.



http://ift.tt/2kCWvON

Foxo3a inhibits mitochondrial fission and protects against doxorubicin-induced cardiotoxicity by suppressing MIEF2

Publication date: Available online 27 January 2017
Source:Free Radical Biology and Medicine
Author(s): Luyu Zhou, Ruibei Li, Cuiyun Liu, Teng Sun, Lynn Htet Htet Aung, Chao Chen, Jinning Gao, Yanfang Zhao, Kun Wang
Doxorubicin (DOX) as a chemotherapeutic drug is widely used to treat a variety of human tumors. However, a major factor limiting its clinical use is its cardiotoxicity. The molecular components and detailed mechanisms regulating DOX-induced cardiotoxicity remain largely unidentified. Here we report that Foxo3a is downregulated in cardiomyocytes and mouse heart in response to DOX treatment. Foxo3a attenuates DOX-induced mitochondrial fission and apoptosis in cardiomyocytes. Cardiac specific Foxo3a transgenic mice show reduced mitochondrial fission, apoptosis and cardiotoxicity upon DOX administration. Furthermore, Foxo3a directly targets mitochondrial dynamics protein of 49kDa (MIEF2) and suppresses its expression at transcriptional level. Knockdown of MIEF2 reduces DOX-induced mitochondrial fission and apoptosis in cardiomyocytes and in vivo. Also, knockdown of MIEF2 protects heart from DOX-induced cardiotoxicity. Our study identifies a novel pathway composed of Foxo3a and MIEF2 that mediates DOX cardiotoxicity. This discovery provides a promising therapeutic strategy for the treatment of cancer therapy and cardioprotection.



http://ift.tt/2kcLsiw

Complementary and alternative medicine in radiation oncology

Abstract

Background

Complementary and alternative medicine (CAM) are gaining in importance, but objective data are mostly missing. However, in previous trials, methods such as acupuncture showed significant advantages compared to standard therapies. Thus, the aim was to evaluate most frequently used methods, their significance and the general acceptance amongst cancer patients undergoing radiotherapy (RT).

Methods

A questionnaire of 18 questions based on the categorical classification released by the National Centre for Complementary and Integrative Health was developed. From April to September 2015, all patients undergoing RT at the Department of Radiation Oncology, Technical University of Munich, completed the survey. Changes in attitude towards CAM were evaluated using the questionnaire after RT during the first follow-up visit (n = 31).

Results

Of 634 patients, 333 answered the questionnaire (52.5%). Of all participants, 26.4% used CAM parallel to RT. Before RT, a total of 39.3% had already used complementary medicine. The most frequently applied methods during therapy were vitamins/minerals, food supplements, physiotherapy/manual medicine, and homeopathy. The majority (71.5%) did not use any complementary treatment, mostly stating that CAM was not offered to them (73.5%). The most common reasons for use were to improve the immune system (48%), to reduce side effects (43.8%), and to not miss an opportunity (37.8%). Treatment integrated into the individual therapy concept, e.g. regular acupuncture, would be used by 63.7% of RT patients.

Conclusion

In comparison to other studies, usage of CAM parallel to RT in our department is considered to be low. Acceptance amongst patients is present, as treatment integrated into the individual oncology therapy would be used by about two-third of patients.

http://ift.tt/2kbSJPC

Thyroid disorders in polycystic ovary syndrome

OBJECTIVE: Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general population – approximately 27% and 8%, respectively. This is extremely important in young women, because both disorders are connected with fertility problems. As HT and PCOS occur together, fertility problems may become a serious clinical issue in these patients.

MATERIALS AND METHODS: A systematic literature review in PubMed of PCOS- and HT-related articles in English, published until December 2015 was conducted.

RESULTS: The reasons for joint prevalence still remain unclear. Genetic and autoimmune backgrounds are recognized to be possible common etiological factors. Three genetic polymorphisms have been described to play a role in PCOS as well as in HT. They are polymorphism of the gene for fibrillin 3 (FBN3) regulating the activity of transforming growth factor-b (TGF-b) and regulatory T cell levels, gonadotropin-releasing hormone receptor (GnRHR) polymorphism and CYP1B1 polymorphism standing for estradiol hydroxylation. High estrogen-to-progesterone ratios owing to anovulatory cycles, as well as high estrogen levels during prenatal life, disrupt development of the thymus and its function in maintaining immune tolerance, and are suspected to enhance autoimmune response in PCOS. Vitamin D deficiency could be also involved in the pathogenesis of HT and PCOS.

CONCLUSIONS: The above-mentioned common etiological factors associated with fertility problems in HT and PCOS require further research.

L'articolo Thyroid disorders in polycystic ovary syndrome sembra essere il primo su European Review.

http://ift.tt/2jmqhX7

Evaluation of maternal history of miscarriage, infertility, and in-vitro fertilization use as associated factors in PHACE

Abstract

The etiology of PHACE (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Coarctation of the aorta, and Eye anomalies) is unknown. A genetic etiology has been proposed but there are no published reports of heritability in families of children with PHACE. PHACE has a female predominance although preliminary X-inactivation studies have not demonstrated significant skewing in affected female patients or their mothers.¹ Copy number variation studies have yet to identify a common pathogenic variant.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jeJJda

The objective Psoriasis Area Severity Index: A randomised controlled pilot study comparing the effectiveness of cyclosporine and methotrexate using an objective PASI (oPASI)

Abstract

A randomised controlled pilot study was performed to compare the clinical effectiveness of cyclosporine and methotrexate, using a new objective severity assessment method, which we then compared with the Psoriasis Area Severity Index (PASI) for usefulness and reliability.

Psoriatic patients with psoriatic lesions over 5% of body surface area were enrolled and underwent 16 weeks of treatment with either cyclosporine or methotrexate. In the cyclosporine group, the initial dose was 150 mg/day for females and 200 mg/day for males.

This article is protected by copyright. All rights reserved.

http://ift.tt/2k1JjDW

Possible inducible skin-associated lymphoid tissues (iSALT)-like structures with CXCL13+ fibroblast-like cells in secondary syphilis

Abstract

Non-lymphoid organs, are not merely the sites for effector T-cell-function.Ectopic accumulations of lymphoid cells arise in non-lymphoid organs under long-lived self-perpetuating chronic inflammation.¹ These accumulations are called tertiary lymphoid organs (TLOs), and they function as antigen-presenting sites.¹ TLOs are characterized by their cellular, organizational, chemokine, and vascular similarity to lymph nodes (LNs).¹

This article is protected by copyright. All rights reserved.

http://ift.tt/2jeODqj

Chronic Urticaria and Atopic Disorders: a Cross-sectional Study of 11,271 Patients

Abstract

Chronic urticaria (CU) and atopic disorders such as atopic dermatitis (AD), allergic rhinoconjunctivitis (AR), and asthma are related to aberrant immune function. The relationship between atopic disorders and CU is controversial, mostly since epidemiological data are lacking.

The aim of our study was to investigate the association between CU and asthma, AD, and AR using a database of Clalit Health Services (CHS) - the largest healthcare provider organization in Israel.

This article is protected by copyright. All rights reserved.

http://ift.tt/2k1v561

BRAF inhibitor-associated cutaneous squamous cell carcinoma: new mechanistic insight, emerging evidence for a viral involvement, and perspectives on clinical management

Abstract

Mutations in the BRAF proto-oncogene occur in the majority of cutaneous melanomas. The commonly detected valine (V) to glutamate (E) mutation (V600E) is known to drive melanomagenesis and has thus been the target of two highly selective chemotherapeutic agents: vemurafenib and dabrafenib. While BRAF inhibitor therapy has revolutionized the treatment of metastatic melanoma, unanticipated cutaneous toxicities including the development of cutaneous squamous cell carcinomas (cSCCs) are frequently reported and hinder therapeutic durability. However, the mechanisms by which BRAF inhibitors induce cutaneous neoplasms are poorly understood, thus posing a challenge for specific therapies. In this review, we summarize the clinical and molecular profile of BRAF inhibitor-associated cSCCs, with a focus on factors that may contribute to disease pathogenesis. In particular, we discuss the emerging evidence pointing toward viral involvement in BRAF inhibitor-induced cutaneous neoplasms and offer new perspectives on future therapeutic interventions. Continued clinical and mechanistic studies along this line will not only allow for better understanding of the pathogenic progression of BRAF inhibitor-induced cSCCs, but also lead to development of new therapeutic and preventative options for patients receiving targeted cancer therapy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jf3hOn

BRAFV600 inhibitor discontinuation after complete response in advanced melanoma. A retrospective analysis of 16 patients

Abstract

BRAF inhibitors (BRAFi) improve progression-free survival and overall survival in patients with advanced melanoma (1,2), with 3 to 6% of patients experiencing complete remission (CR)(1,3). Nevertheless, this efficacy comes at a cost with 90% of patients experiencing at least one adverse event and 45% grade 3 or 4 adverse events (4).

Management of long-term responders is not yet well delineated: safety argues for treatment continuation, because evolution after discontinuation is unknown.

This article is protected by copyright. All rights reserved.

http://ift.tt/2k1PAj3

Non-invasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling

Summary

Background

Protein expression is disturbed in psoriatic stratum corneum. Non-invasive methods for the description of pathophysiological changes and drug profiling in psoriasis are desirable.

Objectives

Undertake large scale non-invasive protein expression studies in psoriatic stratum corneum to identify biomarkers of pathophysiological processes and use them for drug profiling.

Methods

Psoriatic stratum corneum was harvested through repetitive tape-stripping. Non-lesional and lesional stratum corneum, as well as vehicle- and drug-treated lesional stratum corneum samples were collected. Protein extracts from non-lesional and lesional skin biopsies were used for comparison. Calcipotriol-Betamethasone (CB) was used as a reference medication. Proteins extracted from pooled tape strips were quantified using mass spectrometry (MS), western blotting, ELISA and Luminex technologies.

Results

MS-based methods identified 140 proteins differentially expressed in psoriatic stratum corneum. Epidermis development, glycolysis, regulation of apoptosis, cytoskeleton organization and peptide cross-linking were modulated, all reflecting perturbed epidermal differentiation.

Using antibody-based techniques, increased levels of sICAM1, of CXCL1 and CXCL8 attracting neutrophils, of CXCL10 and CCL4 attracting Th1 cells, and of CCL2 and CCL4 attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers TNF, IL12B, IL17A and IL17F in lesional stratum corneum was successful, while the Th2 cytokines IL4, IL5 and IL13, not involved in the disease process, were not detected. The pruritic cytokine IL31 was detected in lesional stratum corneum.

CXCL1, CXCL8, CXCL10 and sICAM, were used to investigate disease remission, ranking three topical treatments according to their known clinical efficacy.

Conclusions

Protein biomarker quantification in psoriatic stratum corneum detects key pathophysiological mechanisms and enables non-invasive drug profiling in translational medicine settings.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jeN1Nq

Multimodal evaluation of the amygdala's functional connectivity

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Rebecca Kerestes, Henry W. Chase, Mary L. Phillips, Cecile D. Ladouceur, Simon B. Eickhoff
The amygdala is one of the most extensively studied human brain regions and undisputedly plays a central role in many psychiatric disorders. However, an outstanding question is whether connectivity of amygdala subregions, specifically the centromedial (CM), laterobasal (LB) and superficial (SF) nuclei, are modulated by brain state (i.e., task vs. rest). Here, using a multimodal approach, we directly compared meta-analytic connectivity modeling (MACM) and specific co-activation likelihood estimation (SCALE)-derived estimates of CM, LB and SF task-based co-activation to the functional connectivity of these nuclei as assessed by resting state fmri (rs-fmri). Finally, using a preexisting resting state functional connectivity-derived cortical parcellation, we examined both MACM and rs-fmri amygdala subregion connectivity with 17 large-scale networks, to explicitly address how the amygdala interacts with other large-scale neural networks. Analyses revealed strong differentiation of CM, LB and SF connectivity patterns with other brain regions, both in task-dependent and task-independent contexts. All three regions, however, showed convergent connectivity with the right ventrolateral prefrontal cortex (VLPFC) that was not driven by high base rate levels of activation. Similar patterns of connectivity across rs-fmri and MACM were observed for each subregion, suggesting a similar network architecture of amygdala connectivity with the rest of the brain across tasks and resting state for each subregion, that may be modified in the context of specific task demands. These findings support animal models that posit a parallel model of amygdala functioning, but importantly, also modify this position to suggest integrative processing in the amygdala.



http://ift.tt/2kcwQQc

Spatiotemporal reconstruction of auditory steady-state responses to acoustic amplitude modulations: Potential sources beyond the auditory pathway

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Ehsan Darestani Farahani, Tine Goossens, Jan Wouters, Astrid van Wieringen
Investigating the neural generators of auditory steady-state responses (ASSRs), i.e., auditory evoked brain responses, with a wide range of screening and diagnostic applications, has been the focus of various studies for many years. Most of these studies employed a priori assumptions regarding the number and location of neural generators. The aim of this study is to reconstruct ASSR sources with minimal assumptions in order to gain in-depth insight into the number and location of brain regions that are activated in response to low- as well as high-frequency acoustically amplitude modulated signals.In order to reconstruct ASSR sources, we applied independent component analysis with subsequent equivalent dipole modeling to single-subject EEG data (young adults, 20–30 years of age). These data were based on white noise stimuli, amplitude modulated at 4, 20, 40, or 80Hz. The independent components that exhibited a significant ASSR were clustered among all participants by means of a probabilistic clustering method based on a Gaussian mixture model.Results suggest that a widely distributed network of sources, located in cortical as well as subcortical regions, is active in response to 4, 20, 40, and 80Hz amplitude modulated noises. Some of these sources are located beyond the central auditory pathway. Comparison of brain sources in response to different modulation frequencies suggested that the identified brain sources in the brainstem, the left and the right auditory cortex show a higher responsiveness to 40Hz than to the other modulation frequencies.



http://ift.tt/2k1Bq1g

Left posterior inferior frontal gyrus is causally involved in reordering during sentence processing

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Philipp Kuhnke, Lars Meyer, Angela D. Friederici, Gesa Hartwigsen
Storage and reordering of incoming information are two core processes required for successful sentence comprehension. Storage is necessary whenever the verb and its arguments (i.e., subject and object) are separated over a long distance, while reordering is necessary whenever the argument order is atypical (e.g., object-first order in German, where subject-first order is typical). Previous neuroimaging work has associated storage with the left planum temporale (PT), and reordering with the left posterior inferior frontal gyrus (pIFG). Here, we tested the causal role of the PT and pIFG in storage and reordering using repetitive transcranial magnetic stimulation (rTMS). We applied either effective rTMS over PT or pIFG, or sham rTMS, while subjects listened to sentences that independently varied storage demands (short vs. long argument–verb distance) and reordering demands (subject– vs. object-first argument order). We found that rTMS over pIFG, but not PT, selectively affected reordering during the processing of sentences with a long argument–verb distance. Specifically, relative to sham rTMS, rTMS over pIFG significantly increased the performance difference between object– and subject-first long-distance sentences. These results demonstrate a causal involvement of left pIFG in reordering during sentence comprehension and thus contribute to a better understanding of the role of the pIFG in language processing.



http://ift.tt/2kcudy0

Encoding, preparation and implementation of novel complex verbal instructions

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Carlos González-García, Juan E. Arco, Ana F. Palenciano, Javier Ramírez, María Ruz
Verbal instructions allow humans to acquire and implement complex novel rules in few seconds. A major question that remains elusive is how the brain represents this information prior to successful task execution. In this experiment, we studied the brain regions involved in representing categorical stimulus information during the encoding of novel instructions, their preparation and also their implementation, as well as the relation of the fidelity of these representations to observable behavior. To do so, we devised a novel instructions paradigm to delimitate these three stages. Using univariate and multivariate analyses of functional magnetic resonance data, our study revealed that the semantic content (faces or letters) of complex novel instructions can be decoded several seconds before the onset of a target, as soon as instructions are encoded. Crucially, the quality of the information represented in domain-general and category-selective regions correlated with subsequent behavioral performance. This suggests that the rapid transformation of novel instructions into coherent behavior is supported by control mechanisms that use available, relevant information about the current rule prior to its execution. In addition, our results highlight the relation between these control processes and others such as prospective memory and maintenance of future intentions.



http://ift.tt/2k1KNhz

Hexamidine salts – applications in skin health and personal care products

Abstract

Hexamidine (HEX) has been used as a preservative in topical preparations since the 1950s. A number of studies also indicate that the molecule plays a beneficial role in skin homeostasis. In this review we describe the physicochemical properties of hexamidine diisethionate (HEX D) and the corresponding hydrochloride salt (HEX H). The biocidal and protease inhibition properties of HEX are outlined as well as the effects of HEX on lipid processing enzymes, corneocyte maturity, stratum corneum thickness and Trans epidermal water loss (TEWL). Skin permeation properties of HEX D and HEX H are summarised and formulation approaches for effective dermal targeting of HEX are discussed.

This article is protected by copyright. All rights reserved.

http://ift.tt/2kCK7Cg

Glasgow Coma Scale for Field Triage of Trauma: A Systematic Review [Internet].

To assess the predictive utility, reliability, and ease of use of the total Glasgow Coma Scale (tGCS) versus the motor component of the Glasgow Coma Scale (mGCS) for field triage of trauma, and effects on clinical decisionmaking and clinical outcomes.

http://ift.tt/2kuJOWS

Silica, Some Silicates, Coal Dust and para-Aramid Fibrils.

This volume evaluates the carcinogenic risks to humans posed by exposure to crystalline and amorphous silica, some silicates (palygorskite, sepiolite, wollastonite, and zeolites other than erionite), coal dust, and para-aramid fibrils. The volume opens with a discussion of the many complexities involved in assessing the cancer risks associated with occupational exposure to inhaled mineral dusts, and the special toxicological considerations required when evaluating the results of experimental studies. Against this background, the first and most extensive monograph evaluates human and animal carcinogenicity data on silica, concentrating on evidence of an increased risk for lung cancer. On the basis of this evaluation, crystalline silica inhaled in the form of quartz or cristobalite from occupational sources was classified as carcinogenic to humans. For amorphous silica, evidence from both epidemiological and experimental studies was judged inadequate, and amorphous silica could not be classified.

http://ift.tt/2kcePSn

Immunotherapy for the treatment of multiple myeloma

Publication date: Available online 27 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade. Genetically engineered T cells, such as chimeric antigen receptor T cells or T cell receptor-engineered T cells, have also shown encouraging results in recent clinical studies of patients with MM. In this paper, we discuss recent progress in immunotherapy for the treatment of MM.



http://ift.tt/2jyfGLV

Serum and tissue markers in colorectal cancer: State of art

Publication date: Available online 27 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Massimiliano Berretta, Lara Alessandrini, Chiara De Divitiis, Guglielmo Nasti, Arben Lleshi, Raffaele Di Francia, Gaetano Facchini, Carla Cavaliere, Carlo Buonerba, Vincenzo Canzonieri
Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade, the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e. bevacizumab, cetuximab, panitumab, aflibercept and regorafenib), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future, the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment. Moreover, molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long-term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of serum and tissue markers according to the recently published English literature. This paper is an extension of the article "Biological and clinical markers in colorectal cancer: state of art" by Cappellani A published in Jan 2010.



http://ift.tt/2kBSESd