Age-Dependent Neuropsychiatric Symptoms in the NF-κB/c-Rel Knockout Mouse Model of Parkinson’s Disease

Non-motor symptoms are frequently observed in Parkinson’s disease (PD) and precede the onset of motor deficits by years. Among them, neuropsychiatric symptoms, including anxiety, depression, and apathy, are increasingly considered as a major challenge for patients with PD and their caregivers. We recently reported that mice lacking the nuclear factor-κB (NF-κB)/c-Rel protein (c-rel–/– mice) develop an age-dependent PD-like pathology and phenotype characterized by the onset of non-motor symptoms, including constipation and hyposmia, starting at 2 months of age, and motor deficits at 18 months. To assess whether c-rel–/– mice also suffer from neuropsychiatric symptoms, in this study we tested different cohorts of wild-type (wt) and c-rel–/– mice at 3, 6, 12, and 18–20 months with different behavioral tests. Mice lacking c-Rel displayed anxiety and depressive-like behavior starting in the premotor phase at 12 months, as indicated by the analysis with the open field (OF) test and the forced swim test with water wheel (FST), respectively. A deficit in the goal-oriented nesting building test was detected at 18–20 months, suggesting apathetic behavior. Taken together, these results indicate that c-rel–/– mice recapitulate the onset and the progression of PD-related neuropsychiatric symptoms. Therefore, this animal model may represent a valuable tool to study the prodromal stage of PD and for testing new therapeutic strategies to alleviate neuropsychiatric symptoms

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer

Abstract Background Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. Methods In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. Results The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0–96.3%) and a false-negative rate of 14.0% (95% CI = 6.3–25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2–93.7%), an accuracy of 94.9% (95% CI = 90.3–97.8%) and a negative predictive value of 92.7% (95% CI = 86.1–96.8%). Conclusion Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered

Different Aaenosine A2A receptor expression in peripheral cells from elderly patients with vascular dementia and Alzheimer's disease

The line between vascular dementia (VaD) and Alzheimer's disease (AD) is often blurred. In this study we investigated whether adenosine A2A receptor (A2AR) expression can be used to differentiate between VaD and AD. We evaluated the expression of this receptor in the peripheral blood mononuclear cells of patients with VaD, mild cognitive impairment, AD, and controls. We found statistically significant lower levels of A2AR mRNA in VaD compared to AD subjects. These data suggest that A2AR expression may help in the differential diagnosis between VaD and AD

Epigenetic Regulation of Fatty Acid Amide Hydrolase in Alzheimer Disease

OBJECTIVE: Alzheimer disease (AD) is a progressive, degenerative and irreversible neurological disorder with few therapies available. In search for new potential targets, increasing evidence suggests a role for the endocannabinoid system (ECS) in the regulation of neurodegenerative processes. METHODS: We have studied the gene expression status and the epigenetic regulation of ECS components in peripheral blood mononuclear cells (PBMCs) of subjects with late-onset AD (LOAD) and age-matched controls (CT). RESULTS: We found an increase in fatty acid amide hydrolase (faah) gene expression in LOAD subjects (2.30 ± 0.48) when compared to CT (1.00 ± 0.14; *p<0.05) and no changes in the mRNA levels of any other gene of ECS elements. Consistently, we also observed in LOAD subjects an increase in FAAH protein levels (CT: 0.75 ± 0.04; LOAD: 1.11 ± 0.15; *p<0.05) and activity (pmol/min per mg protein CT: 103.80 ± 8.73; LOAD: 125.10 ± 4.00; *p<0.05), as well as a reduction in DNA methylation at faah gene promoter (CT: 55.90 ± 4.60%; LOAD: 41.20 ± 4.90%; *p<0.05). CONCLUSIONS: Present findings suggest the involvement of FAAH in the pathogenesis of AD, highlighting the importance of epigenetic mechanisms in enzyme regulation; they also point to FAAH as a new potential biomarker for AD in easily accessible peripheral cells

A Two-Phase Approach to Evaluate and Optimize an Interlibrary Loan Service: The Case Study of Provincia di Brescia

WeanalyzethecasestudyofProvinciadiBrescia,anItalianpublicbody managing libraries in the province of Brescia, in Northern Italy. The public body offers an interlibrary loan service organized as follows. Libraries are divided into established groups, each associated with a fixed route. According to a predetermined calendar, each library is visited by a courier a few times a week. The transportation of the items in the network is performed by an external logistics firm, selected through a reverse auction. To assess the current implementation of the service in terms of routing and transportation costs, we propose a two-phase approach based on machine learning and mixed-integer linear programming, and we evaluate it on the data of 2019. Then, we discuss its applicability in reality, and provide a few insights

Latissimus Dorsi Myocutaneous Flap in Immediate Reconstruction after Salvage Mastectomy Post-Lumpectomy and Radiation Therapy

Background: Breast reconstruction after salvage mastectomy (SM) for recurrent cancer represents a challenge in preradiated patients due to the increased complication rate. Latissimus dorsi myocutaneous flap (LDMF) represents a good reconstructive option due to its versatility, safety, and adaptability. Methods: Fifty-nine patients treated in the Breast Surgery Unit at the University Hospital of Parma (Italy) between January 2010 and December 2017 for ipsilateral breast recurrent cancer, previously treated by partial mastectomy plus whole-breast radiation therapy, were analyzed. They underwent SM and immediate reconstruction with implant-assisted pedicled LDMF. We registered local treatment, oncologic characteristics, complications, capsular contracture rate, DASH test, and BREAST-Q scores. Results: Mean implant volume was 403 g (range 135-650 g). Contralateral operations were 16/59 (27.1%). We obtained complete postoperative pain control in most cases with paracetamol. Medium hospital stay was 2.8 days. We registered 3.4% major complications and 6.8% minor ones. Mean follow-up was 26.65 months (range 3-91.9 months). DASH questionnaire evidenced no disability for 71.19% of patients and minimum disability for 28.81% of them. BREAST-Q Aesthetic Questionnaire obtained 92.72%. No patient developed Baker III or IV capsular contracture. Conclusions: LDMF with implant is a reliable and safe procedure for 1-step breast reconstruction after SM for recurrent cancer in radiated breast. It entails a low rate of major complications, achieving stable and pleasant results without significant upper limb functional impairment, also for elderly women and larger breasts. Thus, a definite role is yet predictable for this flap in the setting of SM in all cases not suitable for free-flap reconstruction

One-step prepectoral breast reconstruction with porcine dermal matrix-covered implant: A protective technique improving the outcome in post-mastectomy radiation therapy setting

Background: Post-mastectomy radiotherapy (PMRT) applied on implant-assisted immediate breast reconstruction (IBR) involves a marked increase in complication rate. The recent opportunity of performing an ADM-assisted prepectoral breast reconstruction (PPBR) raised the hypotesis of a protective interaction between ADM and periprosthetic tissues under PMRT. Methods: We performed a retrospective monocentric analysis of a cohort of consecutively treated patients undergone one-step PPBR between January 2015 and September 2018. The aim is to examine complication rate and aesthetic satisfaction of patients, in order to evaluate if this reconstructive technique could be recommendable in PMRT setting. Group 1 comprised 158 patients not submitted to PMRT and Group 2 twenty-eight patients undergone PMRT. Results: All post-operative complications were not statistically different between the two groups, except for capsular contracture (P=0.011). We obtained very high percentages in all BREAST-Q categories in Group 2 patients: satisfaction with breasts 86.8±13.9, satisfaction with implants 6.5±3.0, high satisfaction for no adverse effects of radiation 15.7±6.8. According to multivariate analysis no risk factor was significantly associated with complications. Conclusions: We may conclude that one-step PPBR with porcine ADM followed by PMRT is well tolerated, with no significant risk of adverse outcomes, at least in the short-term follow-up. These promising outcomes warrant further studies to examine the existence of a protective effect due to ADM integration with subcutaneous tissue