TET1 and TDG Suppress Inflammatory Response in Intestinal Tumorigenesis: Implications for Colorectal Tumors With the CpG Island Methylator Phenotype.

BACKGROUND & AIMS: Aberrant DNA methylation is frequent in colorectal cancer (CRC), but underlying mechanisms and pathologic consequences are poorly understood. METHODS: We disrupted active DNA demethylation genes Tet1 and/or Tdg from ApcMin mice and characterized the methylome and transcriptome of colonic adenomas. Data were compared to human colonic adenocarcinomas (COAD) in The Cancer Genome Atlas. RESULTS: There were increased numbers of small intestinal adenomas in ApcMin mice expressing the TdgN151A allele, whereas Tet1-deficient and Tet1/TdgN151A-double heterozygous ApcMin colonic adenomas were larger with features of erosion and invasion. We detected reduction in global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-mutant ApcMin mice and hypermethylation of CpG islands in Tet1-mutant ApcMin adenomas. Up-regulation of inflammatory, immune, and interferon response genes was present in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. This up-regulation was also seen in murine colonic organoids and human CRC lines infected with lentiviruses expressing TET1 or TDG short hairpin RNA. A 127-gene inflammatory signature separated colonic adenocarcinomas into 4 groups, closely aligned with their microsatellite or chromosomal instability and characterized by different levels of DNA methylation and DNMT1 expression that anticorrelated with TET1 expression. Tumors with the CpG island methylator phenotype (CIMP) had concerted high DNMT1/low TET1 expression. TET1 or TDG knockdown in CRC lines enhanced killing by natural killer cells. CONCLUSIONS: Our findings reveal a novel epigenetic regulation, linked to the type of genomic instability, by which TET1/TDG-mediated DNA demethylation decreases methylation levels and inflammatory/interferon/immune responses. CIMP in CRC is triggered by an imbalance of methylating activities over demethylating activities. These mice represent a model of CIMP CRC.

Biomarkers in Sepsis: A Current Review of New Technologies.

Sepsis syndromes have been recognized since antiquity yet still pose significant challenges to modern medicine. One of the biggest challenges lies in the heterogeneity of triggers and its protean clinical manifestations, as well as its rapidly progressive and lethal nature. Thus, there is a critical need for biomarkers that can quickly and accurately detect sepsis onset and predict treatment response. In this review, we will briefly describe the current consensus definitions of sepsis and the ideal features of a biomarker. We will then delve into currently available and in-development markers of pathogens, hosts, and their interactions that together comprise the sepsis syndrome.

Leishmania donovani Transmission Cycle Associated with Human Infection, Phlebotomus alexandri Sand Flies, and Hare Blood Meals, Israel1.

Cutaneous leishmaniasis caused by Leishmania major or L. tropica and visceral leishmaniasis caused by L. infantum have been reported in Israel. We collected Phlebotomus spp. sand flies in the Negev desert of southern Israel to identify circulating Leishmania spp. Of 22,636 trapped sand flies, 80% were P. alexandri. We sequenced Leishmania-specific internal transcribed spacer 1 fragments and K26 genes. Of 5,019 Phlebotomus female sand flies, 2.5% were Leishmania DNA-positive; 92% of infections were L. donovani. Phylogenetic analyses showed separate clustering of L. donovani and L. infantum. P. alexandri flies positive for L. donovani harbored blood meals from European hares. Leishmania DNA isolated from a patient with cutaneous leishmaniasis who lived in the survey area was identical to L. donovani from P. alexandri flies. We report circulation of L. donovani, a cause of visceral leishmaniasis, in southern Israel. Prompt diagnosis and Leishmania spp. identification are critical to prevent leishmaniasis progression.

Limbic self-neuromodulation as a novel treatment option for emotional dysregulation in premenstrual dysphoric disorder (PMDD); a proof-of-concept study.

AIM: To assess the efficacy of a novel neurofeedback (NF) method, targeting limbic activity, to treat emotional dysregulation related to premenstrual dysphoric disorder (PMDD). METHODS: We applied a NF probe targeting limbic activity using a functional magnetic resonance imaging-inspired electroencephalogram model (termed Amyg-EFP-NF) in a double-blind randomized controlled trial. A frontal alpha asymmetry probe (AAS-NF), served as active control. Twenty-seven participants diagnosed with PMDD (mean age = 33.57 years, SD = 5.67) were randomly assigned to Amyg-EFP-NF or AAS-NF interventions with a 2:1 ratio, respectively. The treatment protocol consisted of 11 NF sessions through three menstrual cycles, and a follow-up assessment 3 months thereafter. The primary outcome measure was improvement in the Revised Observer Version of the Premenstrual Tension Syndrome Rating Scale (PMTS-OR). RESULTS: A significant group by time effect was observed for the core symptom subscale of the PMTS-OR, with significant improvement observed at follow-up for the Amyg-EFP group compared with the AAS group [F(1, 15)=4.968, P = 0.042]. This finding was specifically robust for reduction in anger [F(1, 15) = 22.254, P < 0.001]. A significant correlation was found between learning scores and overall improvement in core symptoms (r = 0.514, P = 0.042) suggesting an association between mechanism of change and clinical improvement. CONCLUSION: Our preliminary findings suggest that Amyg-EFP-NF may serve as an affordable and accessible non-invasive treatment option for emotional dysregulation in women suffering from PMDD. Our main limitations were the relatively small number of participants and the lack of a sham-NF placebo arm.

Artificial Antigen Presenting Cells for Detection and Desensitization of Autoreactive T cells Associated with Type 1 Diabetes.

Autoimmune diseases and in particular type 1 diabetes rely heavily on treatments that target the symptoms rather than prevent the underlying disease. One of the barriers to better therapeutic strategies is the inability to detect and efficiently target rare autoreactive T-cell populations that are major drivers of these conditions. Here, we develop a unique artificial antigen-presenting cell (aAPC) system from biocompatible polymer particles that allows specific encapsulation of bioactive ingredients. Using our aAPC, we demonstrate that we are able to detect rare autoreactive CD4 populations in human patients, and using mouse models, we demonstrate that our particles are able to induce desensitization in the autoreactive population. This system provides a promising tool that can be used in the prevention of autoimmunity before disease onset.

Adapting an evidence-supported optimization program for mental health and sport performance in collegiate athletes to fit youth from ethnic/racial minority and low-income neighborhoods: A National Institutes of Health stage model feasibility study.

The current study addresses the need to empirically develop effective mental health interventions for youth from ethnic/racial minority and low-income neighborhoods. Using Stage Model evaluation methods supported by the National Institutes of Health in the US to address underutilization of mental healthcare among racial/ethnic minority youth, this feasibility study demonstrates empirical adaptation of an innovative sport-specific psychological intervention for use in youth from ethnic/racial minority and low-income neighborhoods. An international group of professionals familiar with sport performance and mental health intervention serving the target population experientially examined the adapted intervention protocols in workshops and provided feedback. Survey results indicated the professionals found the intervention components were easy to administer and likely to be safe, enjoyable, engaging and efficacious for youth mental health and sport performance. The protocols were revised based on feedback from these professionals and the intervention was examined in a case trial involving an Asian American youth who evidenced Social Anxiety Disorder. Case study results indicated the intervention could be implemented with integrity, and severity of psychiatric symptoms and factors interfering with sport performance decreased after intervention implementation. The participant's relationships with family, coaches and teammates were also improved.

Somatic engagement alters subsequent neurobehavioral correlates of affective mentalizing.

Socio-emotional encounters involve a resonance of others' affective states, known as affect sharing (AS); and attribution of mental states to others, known as theory-of-mind (ToM). Empathy necessitates the integration of both processes, yet their interaction during emotional episodes and subsequent generation of inferences on others' affective states has rarely been tested. To address this, we developed a novel experimental design, wherein we manipulated AS by presenting nonverbal emotionally negative movies twice-each time accompanied by one of two soundtracks that accentuated either somatic cues or externally generated sounds. Movies were followed by questions addressing affective-ToM (emotional inferences), cognitive-ToM (inferences on beliefs and knowledge), and non-ToM aspects. Results revealed a neural differentiation between AS, affective-ToM, and cognitive-ToM. AS movies activated regions that have been implicated in emotional (e.g., amygdala) and somatosensory processing, and synchronized brain activity between participants in the latter. Affective-ToM activated the middle insula, limbic regions, and both ventral and dorsal portions of the medial prefrontal cortex (ventral medial prefrontal cortex [VMPFC] and dorsal medial prefrontal cortex [DMPFC], respectively), whereas cognitive-ToM activated posteromedial and lateral-prefrontal and temporal cortices. Critically, AS movies specifically altered neural activation in AS and ToM-related regions during subsequent affective-ToM inferences, most notably in the DMPFC. Moreover, DMPFC-VMPFC connectivity correlated with affective-ToM accuracy, when such questions followed AS movies. Our results associate empathic processes with designated neural activations and shed light on how neuro-behavioral indices of affective ToM are shaped by preceding somatic engagement.

An Early Unexpected Immune Thrombotic Thrombocytopenic Purpura Relapse Associated with SARS-CoV-2 Infection: A Case Report and Literature Review.

SARS-CoV-2 has been reported as a possible triggering factor for the development of several autoimmune diseases and inflammatory dysregulation. Here, we present a case report of a woman with a history of systemic lupus erythematosus and antiphospholipid syndrome, presenting with concurrent COVID-19 infection and immune thrombotic thrombocytopenic purpura (TTP). The patient was treated with plasma exchange, steroids, and caplacizumab with initial good response to therapy. The course of both TTP and COVID-19 disease was mild. However, after ADAMTS-13 activity was normalized, the patient experienced an early unexpected TTP relapse manifested by intravascular hemolysis with stable platelet counts requiring further treatment. Only 3 cases of COVID-19 associated TTP were reported in the literature thus far. We summarize the literature and suggest that COVID-19 could act as a trigger for TTP, with good outcomes if recognized and treated early.

Multimodal immersive trail making-virtual reality paradigm to study cognitive-motor interactions.

BACKGROUND: Neuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention-one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test-retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function. METHODS: Healthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance. RESULTS: Construct validity was substantiated by moderate correlations between the'gold standard' pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test-retest reliability (intraclass correlation; VR: tA 0.60-0.75, tB 0.59-0.89; original: tA 0.75-0.85, tB 0.77-0.80) and discriminant validity (area under the curve; VR: tA 0.70-0.92, tB 0.71-0.92; original: tA 0.73-0.95, tB 0.77-0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants. CONCLUSIONS: The present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.

ß-TrCP upregulates HIF-1 in prostate cancer cells.

The substantial availability of hypoxia-inducible factor 1 (HIF-1) for pathophysiological states, such as malignancies and ischemia, is primarily regulated post-translationally through the ubiquitin proteolytic system. The balance between degradation and stabilization of HIF-1α protein is determined by specific E3 ligases. In our search for new E3 ligases that might affect HIF-1α protein expression, we studied the effects of beta-transducin repeat-containing protein (ß-TrCP) on the hypoxic pathway in cancer cells. ß-TrCP is overexpressed in many tumors and regulates various cellular processes through mediating the degradation of important targets. Unexpectedly, we found that ß-TrCP overexpression increases HIF-1α protein expression level as well as HIF-1 transcriptional activity by stabilizing HIF-1α protein and preventing its ubiquitination and proteasomal degradation in prostate cancer cells. By using a proteomic approach, we succeeded in demonstrating that ß-TrCP interferes with the association between HIF-1α and HSP70/CHIP, a HIF-1α established E3 ligase complex. Whereas the E3 ligase activity of ß-TrCP is well known, antagonizing another E3 ligase is a new mechanism of action of this important E3. We suggest that destroying or suppressing ß-TrCP and thereby interrupting the HIF-1 pathway, could be valuable antitumor therapy.

Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study.

BACKGROUND: Ketamine has been demonstrated to improve depressive symptoms.AimsEvaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD). METHOD: In a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Twenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient. CONCLUSIONS: Repeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.Declaration of interestNone.

Robust inter-subject audiovisual decoding in functional magnetic resonance imaging using high-dimensional regression.

Major methodological advancements have been recently made in the field of neural decoding, which is concerned with the reconstruction of mental content from neuroimaging measures. However, in the absence of a large-scale examination of the validity of the decoding models across subjects and content, the extent to which these models can be generalized is not clear. This study addresses the challenge of producing generalizable decoding models, which allow the reconstruction of perceived audiovisual features from human magnetic resonance imaging (fMRI) data without prior training of the algorithm on the decoded content. We applied an adapted version of kernel ridge regression combined with temporal optimization on data acquired during film viewing (234 runs) to generate standardized brain models for sound loudness, speech presence, perceived motion, face-to-frame ratio, lightness, and color brightness. The prediction accuracies were tested on data collected from different subjects watching other movies mainly in another scanner. Substantial and significant (QFDR<0.05) correlations between the reconstructed and the original descriptors were found for the first three features (loudness, speech, and motion) in all of the 9 test movies (R¯=0.62, R¯ = 0.60, R¯ = 0.60, respectively) with high reproducibility of the predictors across subjects. The face ratio model produced significant correlations in 7 out of 8 movies (R¯=0.56). The lightness and brightness models did not show robustness (R¯=0.23, R¯ = 0). Further analysis of additional data (95 runs) indicated that loudness reconstruction veridicality can consistently reveal relevant group differences in musical experience. The findings point to the validity and generalizability of our loudness, speech, motion, and face ratio models for complex cinematic stimuli (as well as for music in the case of loudness). While future research should further validate these models using controlled stimuli and explore the feasibility of extracting more complex models via this method, the reliability of our results indicates the potential usefulness of the approach and the resulting models in basic scientific and diagnostic contexts.

Analysis of false-negative readings of automated breast ultrasound studies.

BACKGROUND: To assess the reasons for false-negative readings of automated breast ultrasound (ABUS) studies. METHODS: Between 2012 and 2015, 1,890 ABUS studies were performed at our tertiary medical center. Those for which false-negative results were documented in the initial ABUS report against the corresponding hand-held ultrasound (HHUS) scan were reviewed by three specialized breast radiologists. Key images of specific lesions were marked on the ABUS and HHUS scans and compared for quality (equal, better with HHUS, better with ABUS). Readers were also asked to identify the reasons for the differences in image quality between the scans: poor visibility, lesion location, or fibroglandular tissue shadowing. RESULTS: Twenty-two ABUS studies met the study criteria. Two of the three readers found that most lesions were better demonstrated with HHUS. Overall agreement among the readers was moderate (kappa 0.36, SD 0.15, p = 0.002). Highest agreement was found for better image quality for HHUS than ABUS (kappa 0.4, SD 1.3, p = 0.0007). Of the four biopsy-proven carcinomas, three were found by all three readers to be better depicted with HHUS; two were located peripherally and were not seen by ABUS. For all readers, the most common reason for false-negative readings was poor visibility, followed by peripheral lesion location and shadowing obscuring the lesion. CONCLUSIONS: Several factors may make reading ABUS images difficult. Resolution can be diminished by imperfect transducer-breast contact, and fibrotic breasts can cause artifacts such as marked shadowing. Peripheral lesions may be missed because of blind spots. Reader training and experience may play an important role in managing these issues. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:245-251, 2017.

Functional connectivity dynamics during film viewing reveal common networks for different emotional experiences.

Recent theoretical and empirical work has highlighted the role of domain-general, large-scale brain networks in generating emotional experiences. These networks are hypothesized to process aspects of emotional experiences that are not unique to a specific emotional category (e.g., "sadness," "happiness"), but rather that generalize across categories. In this article, we examined the dynamic interactions (i.e., changing cohesiveness) between specific domain-general networks across time while participants experienced various instances of sadness, fear, and anger. We used a novel method for probing the network connectivity dynamics between two salience networks and three amygdala-based networks. We hypothesized, and found, that the functional connectivity between these networks covaried with the intensity of different emotional experiences. Stronger connectivity between the dorsal salience network and the medial amygdala network was associated with more intense ratings of emotional experience across six different instances of the three emotion categories examined. Also, stronger connectivity between the dorsal salience network and the ventrolateral amygdala network was associated with more intense ratings of emotional experience across five out of the six different instances. Our findings demonstrate that a variety of emotional experiences are associated with dynamic interactions of domain-general neural systems.

Functional comparison of engineered T cells carrying a native TCR versus TCR-like antibody-based chimeric antigen receptors indicates affinity/avidity thresholds.

Adoptive transfer of Ag-specific T lymphocytes is an attractive form of immunotherapy for cancers. However, acquiring sufficient numbers of host-derived tumor-specific T lymphocytes by selection and expansion is challenging, as these cells may be rare or anergic. Using engineered T cells can overcome this difficulty. Such engineered cells can be generated using a chimeric Ag receptor based on common formats composed from Ag-recognition elements such as αß-TCR genes with the desired specificity, or Ab variable domain fragments fused with T cell-signaling moieties. Combining these recognition elements are Abs that recognize peptide-MHC. Such TCR-like Abs mimic the fine specificity of TCRs and exhibit both the binding properties and kinetics of high-affinity Abs. In this study, we compared the functional properties of engineered T cells expressing a native low affinity αß-TCR chains or high affinity TCR-like Ab-based CAR targeting the same specificity. We isolated high-affinity TCR-like Abs recognizing HLA-A2-WT1Db126 complexes and constructed CAR that was transduced into T cells. Comparative analysis revealed major differences in function and specificity of such CAR-T cells or native TCR toward the same antigenic complex. Whereas the native low-affinity αß-TCR maintained potent cytotoxic activity and specificity, the high-affinity TCR-like Ab CAR exhibited reduced activity and loss of specificity. These results suggest an upper affinity threshold for TCR-based recognition to mediate effective functional outcomes of engineered T cells. The rational design of TCRs and TCR-based constructs may need to be optimized up to a given affinity threshold to achieve optimal T cell function.

A Dedicated Follow-Up Clinic for BRCA Mutation Carriers.

BACKGROUND: Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33-68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a "home" for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Value of ultrasound in detecting central compartment lymph node metastases in differentiated thyroid carcinoma.

The value of ultrasound in detecting central compartment lymph node metastasis in patients with well-differentiated thyroid carcinoma (WDTC) is unclear. Prospective patients with WDTC attending a university-affiliated tertiary medical center between July 2010 and June 2011 underwent neck ultrasound for detection of central compartment lymph node metastases prior to surgery. Central lymph node dissection was performed during the initial surgery regardless of ultrasound findings. The sensitivity and specificity of preoperative ultrasound in detecting central lymph node metastases were calculated according to the final histopathological results. Sixty-four patients met the study criteria. Twenty-four had pathologic central compartment lymph nodes according to preoperative ultrasound, 20 of which were confirmed by histological examination. One patient was found to have pathological central lymph nodes by histology which was not detected by US. Sensitivity of preoperative ultrasound was 95%, specificity 90%, and negative and positive predictive values 97 and 83%, respectively. Preoperative ultrasound may serve as an accurate and important tool for deciding the extent of surgery in WDTC.

Melanoma cells present high levels of HLA-A2-tyrosinase in association with instability and aberrant intracellular processing of tyrosinase.

Short-lived protein translation products are proposed to be a major source of substrates for major histocompatibility complex (MHC) class I antigen processing and presentation; however, a direct link between protein stability and the presentation level of MHC class I-peptide complexes has not been made. We have recently discovered that the peptide Tyr((369-377)) , derived from the tyrosinase protein is highly presented by HLA-A2 on the surface of melanoma cells. To examine the molecular mechanisms responsible for this presentation, we compared characteristics of tyrosinase in melanoma cells lines that present high or low levels of HLA-A2-Tyr((369-377)) complexes. We found no correlation between mRNA levels and the levels of HLA-A2-Tyr((369-377)) presentation. Co-localization experiments revealed that, in cell lines presenting low levels of HLA-A2-Tyr((369-377)) complexes, tyrosinase co-localizes with LAMP-1, a melanosome marker, whereas in cell lines presenting high HLA-A2-Tyr((369-377)) levels, tyrosinase localizes to the endoplasmic reticulum. We also observed differences in tyrosinase molecular weight and glycosylation composition as well as major differences in protein stability (t(1/2) ). By stabilizing the tyrosinase protein, we observed a dramatic decrease in HLA-A2-tyrosinase presentation. Our findings suggest that aberrant processing and instability of tyrosinase are responsible for the high presentation of HLA-A2-Tyr((369-377)) complexes and thus shed new light on the relationship between intracellular processing, stability of proteins, and MHC-restricted peptide presentation.

A novel functional infrared imaging system coupled with multiparametric computerised analysis for risk assessment of breast cancer.

OBJECTIVE: We evaluated a functional three-dimensional (3D) infrared imaging system (3DIRI) coupled with multiparametric computer analysis for risk assessment of breast cancer. The technique provides objective risk assessment for the presence of a malignant tumour based on automated parameters derived from a clinically known training set. METHODS: Following institutional review board approval, we recruited 434 women for this prospective multicentre trial, including 256 healthy woman undergoing routine screening mammography with BI-RADS-1 results and 178 women with newly diagnosed breast cancer. This was a two-phase study: an initial training and calibration phase, followed by a two-armed blinded evaluation phase (52 healthy and 66 with breast cancer). 3DIRI data sets were acquired using a non-contact, no radiation system. RESULTS: The sensitivity and specificity of functional infrared imaging in providing the correct risk for the presence of breast cancer were 90.9 % and 72.5 %, respectively. The area under the ROC curve was 86 %. Forty-two of the 60 (70 %) cancers in women correctly classified by the system as suspicious were smaller than 20 mm in size. CONCLUSION: The preliminary blinded results of this novel technology show sufficient performance of functional infrared imaging in providing risk assessment for breast cancer to warrant further clinical studies. KEY POINTS: • 3D functional infrared imaging (3DIRI) provides new metabolic signatures from breast lesions. • 3DIRI offers high sensitivity for risk assessment of breast cancer. • It also has reasonable specificity. • This initial experience warrants further evaluation in larger clinical trials.

Urinary Incontinence in Parous Women Practicing Non-Extreme Competitive Sports Compared to the General Population.

INTRODUCTION AND OBJECTIVE: This cross-sectional study aimed to compare the prevalence of urinary symptoms in physically active females to the general population represented by medical staff. MATERIALS AND METHODS: We conducted a survey utilizing the UDI-6 questionnaire on women playing catchball for at least one year and training twice a week or more in an official Israeli competitive league. The control group consisted of women practicing medicine (physicians and nurses). RESULTS: The study group consisted of 317 catchball players and the control group consisted of 105 medical staff practitioners. Both groups were similar in most of the demographic characteristics. Urinary symptoms represented by UDI-6 scores were higher in women in the catchball group. Frequency and urgency symptoms were common in women playing catchball. Stress urinary incontinence (SUI) was insignificant between the groups (43.8% in the catchball group and 35.2% in the medical staff group, p = 0.114). However, severe symptoms of SUI were more common in catchball players. CONCLUSIONS: The rates of all urinary symptoms were higher in in catchball players. SUI symptoms were common in both groups. However, severe symptoms of SUI were more common in catchball players.