Central nesfatin-1-expressing neurons are sensitive to peripheral inflammatory stimulus

Recently, a novel factor with anorexigenic properties was identified and called nesfatin-1. This protein (82 aac) is not only expressed in peripheral organs but it is also found in neurons located in specific structures including the hypothalamus and the brainstem, two sites strongly involved in food intake regulation. Here, we studied whether some of the neurons that become activated following an injection of an anorectic dose of lipopolysaccharides (LPS) exhibit a nesfatin-1 phenotype. To this end, we used double immunohistochemistry to target the expression of the immediate-early gene c-fos and of nesfatin-1 on coronal frozen sections of the rat brain. The number of c-Fos+/nesfatin-1+ neurons was evaluated in the immunosensitive structures reported to contain nesfatin-1 neurons; i.e. paraventricular hypothalamic nucleus (PVN), supraoptic nucleus (SON), arcuate nucleus (ARC) and nucleus of the solitary tract (NTS). LPS strongly increased the number of c-Fos+/nesfatin-1+ neurons in the PVN, SON and NTS, and to a lesser extent in the ARC. Triple labeling showed that a portion of the nesfatin-1 neurons activated in response to LPS within the NTS are catecholaminergic since they co-express tyrosine hydroxylase (TH). Our data therefore indicate that a portion of nesfatin-1 neurons of both the hypothalamus and brainstem are sensitive to peripheral inflammatory signals, and provide the first clues suggesting that centrally released nesfatin-1 may contribute to the neural mechanisms leading to endotoxaemic anorexia

Estimating VAIA windstorm damaged forest area in Italy using time series Sentinel-2 imagery and continuous change detection algorithms

Mapping forest disturbances is an essential component of forest monitoring systems both to support local decisions and for international reporting. Between the 28 and 29 October 2018, the VAIA storm hit the Northeast regions of Italy with wind gusts exceeding 200 km h−1. The forests in these regions have been seriously damaged. Over 490 Municipalities in six administrative Regions in Northern Italy registered forest damages caused by VAIA, that destroyed or intensely damaged forest stands spread over an area of 67,000 km2. The present work tested the use of two continuous change detection algorithms, i.e., the Bayesian estimator of abrupt change, seasonal change, and trend (BEAST) and the continuous change detection and classification (CCDC) to map and estimate forest windstorm damage area using a normalized burned ration (NBR) time series calculated on three years Sentinel-2 (S2) images collection (i.e., January 2017–October 2019). We analyzed the accuracy of the maps and the damaged forest area using a probability-based stratified estimation within 12 months after the storm with an independent validation dataset. The results showed that close to the storm (i.e., 1 to 6 months November 2018–March 2019) it is not possible to obtain accurate results independently of the algorithm used, while accurate results were observed between 7 and 12 months from the storm (i.e., May 2019 – October 2019) in terms of Standard Error (SE), percentage SE (SE%), overall accuracy (OA), producer accuracy (PA), user accuracy (UA), and gmean for both BEAST and CCDC (SE< 3725.3 ha, SE% < 9.69, OA > 89.7, PA and UA > 0.87, gmean > 0.83)

Predictive Role Of Body Composition Parameters In Operable Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BACKGROUND: Fat tissue is strongly involved in BC tumorigenesis inducing insulin resistance, chronic inflammation and hormonal changes. Computed tomography (CT) imaging instead of body mass index (BMI) gives a reliable measure of skeletal muscle mass and body fat distribution. The impact of body composition parameters (BCPs) on chemosensitivity is still debated. We examined the associations between BCPs and tumor response to neoadjuvant chemotherapy (NC) in patients treated for operable breast cancer (BC). METHODS: A retrospective review of BC patients treated with NC in Modena Cancer Center between 2005 and 2017 was performed. BCPs, such as subcutaneous fat area (SFA), visceral fat area (VFA), lumbar skeletal muscle index (LSMI) and liver-to-spleen (L/S) ratio were calculated by Advance workstation (General Electric), software ADW server 3.2 or 4.7. BMI and BCPs were correlated with pathological complete response (pCR) and survival outcomes. RESULTS: 407 patients were included in the study: 55% with BMI < 25 and 45% with BMI 65 25. 137 of them had pre-treatment CT scan imagines. Overweight was significantly associated with postmenopausal status and older age. Hormonal receptor positive BC was more frequent in overweight patients (p<0.05). Postmenopausal women had higher VFA, fatty liver disease and obesity compared to premenopausal patients. No association between BMI classes and tumor response was detected. High VFA and liver steatosis were negative predictive factors for pCR (pCR rate: 36% normal VFA vs 20% high VFA, p= 0.048; no steatosis 32% vs steatosis 13%, p=0.056). Neither BMI classes nor BCPs significantly influenced overall survival and relapse-free survival. CONCLUSION: Visceral adiposity as well as steatosis were closely involved in chemosensitivity in BC patients treated with NC. Their measures from clinically acquired CT scans provide significant predictive information that outperform BMI value. More research is required to evaluate the relationship among adiposity site and survival outcomes

Inverse Association of Longitudinal Variations in Fat Tissue Radiodensity and Area

Increased CT-derived fat tissue radiodensity has been indicated as a poor prognostic factor in oncological settings, although the reasons are not clear. One hypothesis is that increased radiodensity may reflect the loss of fat droplets within adipocytes, being a proxy of recent weight loss. This study aims to test this hypothesis by evaluating the association between longitudinal variations in fat tissue radiodensity and area in a cohort of COVID-19 patients. Baseline and 2-3-month follow-up chest CT scans of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure subcutaneous, visceral, and intermuscular adipose tissue (SAT, VAT, and IMAT) areas and densities at the T7-T8 vertebrae, and longitudinal variations were computed for each variable. The associations between each compartment area and radiodensity variations (standardized values) were evaluated in univariate linear models and models adjusted by age and sex. A total of 196 COVID-19 survivors with suitable baseline and follow-up CT scans were included (mean age 65 +/- 11 years, 62 (31.6%) females, 25% with diabetes and 2.6% with morbid obesity). Longitudinal variation in SAT area was inversely associated with longitudinal variation in SAT radiodensity in univariate models (coeff -0.91, 95%CI = -1.70/-0.12, p = 0.02) and after adjustment by age and sex (coeff -0.89, 95%CI = -1.7/-0.09, p = 0.03). The effect was similar and stronger for IMAT (coeff -2.1, 95%CI = -3.06/-1.19, p < 0.01 in adjusted models), and absent for VAT. Longitudinal variations in subcutaneous and intermuscular adipose tissue areas and densities are inversely associated. Higher adipose tissue radiodensity may be due to decrease in fat area (i.e., weight loss), explaining the poor prognostic effect found in cancer patients

The Prognostic Role of Early Skeletal Muscle Mass Depletion in Multimodality Management of Patients with Advanced Gastric Cancer Treated with First Line Chemotherapy: A Pilot Experience from Modena Cancer Center

Background: Few data about the link between nutritional status and survival are available in the metastatic gastric cancer (GC) setting. The aim of this work was to evaluate the prognostic role of tissue modifications during treatment and the benefit of a scheduled nutritional assessment in this setting. Methods: Clinical and laboratory variables of 40 metastatic GC patients treated at Modena Cancer Center were retrieved: 20 received a nutritional assessment on the oncology’s discretion, the other 20 received a scheduled nutritional assessment at baseline and every 2–4 weeks. Anthropometric parameters were calculated on Computed Tomography (CT) images at the baseline and after 3 months of chemotherapy. Results: A correlation between baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS), Lymphocyte to Monocyte Ratio (LMR), C-reactive protein (PCR), Prognostic Nutritional Index (PNI) and Overall survival (OS) was highlighted. Among the anthropometric parameters, early skeletal muscle mass depletion (ESMMD) >10% in the first months of treatment significantly impacted on mOS (p = 0.0023). A link between ESMMD and baseline LDH > 460 U/L, baseline CRP > 2.2 mg/dL and weight decrease during treatment emerged. Patients evaluated with a nutritional scheduled support experienced a mean gain in subcutaneous and visceral fat of 11.4% and 10.21%, respectively. Conclusion: We confirm the prognostic impact of ESMMD > 10% during chemotherapy in metastatic GC. The prognostic role of a scheduled nutritional assessment deserves further confirmation in large prospective trials

Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience

BACKGROUND: Breast cancer (BC) detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. METHODS: We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44) were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC). The standardized incidence ratio (SIR) was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. RESULTS: After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI) = 1.6 to 7.6; p < 0.001]. The incidence observed among BRCA carriers (SIR = 20.3; 95% CI = 3.1 to 83.9; P < 0.001), women at increased (SIR = 4.5; 95% CI = 1.5 to 8.3; P < 0.001) or intermediate risk (SIR = 7.0, 95% CI = 2.0 to 17.1; P = 0.0018) was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74). CONCLUSION: The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in the slightly increased risk group. These results support the effectiveness of the proposed program to identify and monitor individuals at high risk, whereas prospective trials are needed for women belonging to families with sporadic BC or OC