Metastasis Upregulated Genes Have Distinct Function in C. elegans Cell Migrations

Cell migration is vital for normal animal development but also contributes to the invasive spreading of early stage metastatic cancer. From two published databases, we complied 107 genes unregulated in either breast cancer or melanoma metastases and investigated their requirement in two Caenorhabditis elegans cell migrations: the male linker cell (LC) and hermaphrodite distal tip cells (DTC) which have similar functions as gonadal leader cells that undergo a complex migration while pulling non-motile followers. We performed an RNAi screen to identify genes implicated in normal LC and DTC migrations. Thirty-two genes from the metastasis list were required for the cell migration of which 13 genes effected the migration of both LC and DTC, 18 genes effected only LC migration, and 4 genes only DTC migration. The genes used by both cell types corresponded to genes involved in cell cycle activity, adhesion, cytoskeleton organization, protein degradation activity, spliceosome activity, ubiquitin-like modification and function, and peptidase inhibition. The genes used by only the LC corresponded to genes involved in adhesion, cytoskeletal organization, methyltransferase activity, metalloproteinase activity, and signaling. Those genes used by only DTC corresponded to genes involved in signaling, peptidase inhibition, and utrophin activity. The significant differences among the developmental cell migrations and the overlap in genes shared between the two metastases underscores the value of characterizing diverse genes and considering cell type in developing treatments

Screening for eating disorders: false negatives and eating disorders not otherwise specified

OBJECTIVE: To study the problem of false negatives in the screening for eating disorders. SUBJECTS AND METHODS: We administered the Eating Attitudes Test (EAT40) and the Eating Disorder Inventory (EDI) to 186 Italian female students (age 17.68 ± 0.9; BMI 20.84 ± 2.69). Then we submitted not only high-scorers but also all the subjects to a semi-structured diagnostic interview (Eating Disorder Examination - EDE 12.0D). The diagnosis of eating disorders not otherwise specified (EDNOS) was applied to cases which met all the DSM-IV criteria for AN and/or BN with one exception. RESULTS: 17 girls (9.1%) fulfilled diagnostic criteria for eating disorders: 1 bulimia nervosa full-syndrome and 16 EDNOS. Of the 17 girls 11 were EAT low-scorers (< 30) and 8 were EDI low-scorers (< 50); 5 subjects scored below the cutoff on both instruments. We calculated sensitivity (35.3%), specificity (88.8%), positive predictive value (PPV, 24.0%) and negative predictive value (NPV, 93.2%) of the EAT40; the respective values for the EDI were 52.9% (sensitivity), 85.2% (specificity), 26.4% (PPV) and 94.7% (NPV). DISCUSSION AND CONCLUSION: Our data show that the introduction of the EDNOS diagnoses increases the PPV of the two questionnaires but lowers their sensitivity. We conclude that using a two stage screening approach leads to a very high rate of false negatives with a significant underestimation of the prevalence of eating disorders, particularly of EDNOS

Validating the Body Uneasiness Test (BUT) in obese patients

OBJECTIVE: To investigate the psychometric properties of the Body Uneasiness Test (BUT) in a large sample of subjects with obesity seeking treatment. BUT is a 71-item self-report questionnaire in two parts: BUT-A which measures weight phobia, body image concerns, avoidance, compulsive self-monitoring, detachment and estrangement feelings towards one’s own body (depersonalization); and BUT-B, which looks at specific worries about particular body parts or functions. METHODS: We recruited a clinical sample of 1,812 adult subjects (age range 18-65 years, females 1,411, males 401) with obesity (Body Mass Index, BMI ≥30 kg/m2) and a normal weight (BMI value between 18.5 and 25 kg/m2) non-clinical sample of 457 adult subjects (females 248, males 209) with an Eating Attitudes Test-26 (EAT-26) score under the cut-off point 20 (scores ≥20 indicate possible cases of eating disorders). RESULTS: The exploratory and confirmatory analyses confirmed a structural five-factor model for BUT-A and an eight-factor model for BUT-B. Internal consistency was satisfactory. Concurrent validity with Binge Eating Scale (BES) and Three-Factor Eating Questionnaire (TFEQ) was evaluated. The authors calculated mean values for BUT scores in adult (18-65 years) patients with obesity, and evaluated the influence of gender, age and BMI. Females obtained statistically significant higher scores than males in all age groups and in all classes of obesity; patients with obesity, compared with normal weight subjects, generally obtained statistically significant higher scores, but few differences could be attributed to the influence of BMI. CONCLUSION: The BUT can be a valuable multidimensional tool for the clinical assessment of body uneasiness in obesity; the scores of its sub-scales do not show a linear correlation with BMI values

Thermal Imaging of Nanostructures by Quantitative Optical Phase Analysis

International audienceWe introduce an optical microscopy technique aimed at characterizing the heat generation arising from nanostructures, in a comprehensive and quantitative manner. Namely, the technique permits (i) mapping the temperature distribution around the source of heat, (ii) mapping the heat power density delivered by the source, and (iii) retrieving the absolute absorption cross section of light-absorbing structures. The technique is based on the measure of the thermal-induced refractive index variation of the medium surrounding the source of heat. The measurement is achieved using an association of a regular CCD camera along with a modified Hartmann diffraction grating. Such a simple association makes this technique straightforward to implement on any conventional microscope with its native broadband illumination conditions. We illustrate this technique on gold nanoparticles illuminated at their plasmonic resonance. The spatial resolution of this technique is diffraction limited, and temperature variations weaker than 1 K can be detected

Expression and Function of Osteopontin in Vascular Adventitial Fibroblasts and Pathological Vascular Remodeling

Osteopontin is known to play important roles in various diseases including vascular disorders. However, little is known about its expression and function in vascular adventitial fibroblasts. Adventitial fibroblasts have been shown to play a key role in pathological vascular remodeling associating with various vascular disorders. In this study, we measured activation of Osteopontin and its biological functions in cultured adventitial fibroblasts and injured rat carotid injury arteries induced by balloon angioplasty. Our results showed that angiotensin II and aldosterone increased Osteopontin expression in adventitial fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1 pathways were involved in Osteopontin upregulation. In addition, Adventitial fibroblast migration stimulated by Angiotensin II and aldosterone required OPN expression. Perivascular delivery of antisense oligonucleotide for Osteopontin suppressed neointimal formation post-injury. We concluded that upregulation of Osteopontin expression in adventitial fibroblasts might be important in the pathogenesis of vascular remodeling after arterial injury

Arginine Metabolism by Macrophages Promotes Cardiac and Muscle Fibrosis in mdx Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD.We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial effects of short-term treatments.Our findings demonstrate that arginine metabolism by arginase promotes fibrosis of muscle in muscular dystrophy and contributes to kyphosis. Our findings also show that long-term, dietary supplementation with arginine exacerbates fibrosis of dystrophic heart and muscles. Thus, commonly-practiced dietary supplementation with arginine by DMD patients has potential risk for increasing pathology when performed for long periods, despite reports of benefits acquired with short-term supplementation

Histology and PSMA Expression on Immunohistochemistry in High-Risk Prostate Cancer Patients: Comparison with 68Ga-PSMA PET/CT Features in Primary Staging

PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44–50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes

Nd3+ activated CaF2 NPs as colloidal nanothermometers in the biological window

CaF2 nanoparticles activated with Nd3þ ions have been investigated as potential optical nanothermometers in the biological windows. The variation of the Nd3þ emission around 850 and 1060 nm as a function of the temperature has been measured. A ratiometric approach, based on the relative changes in the intensities of different emission bands of the Nd3þ has been considered to investigate the thermometric properties of the NPs. The evaluated thermal sensitivity is around 0.12% K1, a value that is similar to those found for other water dispersible nanothermometers based on the near-infrared luminescence of the Nd3þ lanthanide ion. The temperature uncertainty is around 1.8 C, small enough to monitor the local temperature during a photothermal treatment