Neurochemical and Behavioral Characterization after Acute and Repeated Exposure to Novel Synthetic Cannabinoid Agonist 5-MDMB-PICA

Since the early 2000s, herbal mixtures containing synthetic cannabinoids (SCs), broadly known as Spice/K2, have been marketed as a legal marijuana surrogate and have become very popular among adolescents. Adolescence is a critical period of development, which is associated with an increased vulnerability to the central effects of drugs. Despite growing concerns about the negative effects of the use of SCs, newly synthetized compounds are increasingly detected in drugs seized by the authorities, posing a serious threat to public health. 5F-MDMB-PICA has been recently detected and classified as a highly potent agonist of CB1 and CB2 cannabinoid receptors. Here, we first investigated the rewarding properties of 5F-MDMB-PICA in C57BL/6 adolescent and adult mice by in vivo brain microdialysis. Data showed that acute administration of a selected dose of 5F-MDMB-PICA (0.01 mg/kg i.p.) stimulates the release of dopamine in the nucleus accumbens shell of adolescent, but not of adult, mice. To further investigate the consequences of repeated exposure to this dose of 5F-MDMB-PICA, a separate group of adolescent mice was treated for 14 consecutive days and evaluated for behavioral abnormalities at adulthood, starting from 7 days after drug discontinuation. Data showed that this group of adult mice displayed an anxiety-like and compulsive-like state as revealed by an altered performance in the marble burying test. Our study suggests an alarming vulnerability of adolescent mice to the effects of 5F-MDMB-PICA. These findings provide a useful basis for understanding and evaluating both early and late detrimental effects that may derive from the use of SCs during adolescence

Overall treatment strategy for patients with metastatic NSCLC with activating EGFR mutations

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) are standard of care in the first-line (1L) setting for patients with metastatic non-small cell lung cancer (mNSCLC) with activating EGFR mutations. EGFR activating mutations are a predictive factor for response to EGFR-TKIs. Meta-analyses have shown that patients with exon 21_L858R mutations exhibit reduced sensitivity to EGFR-TKIs, resulting in inferior patient outcomes compared to those with exon 19 deletion mutations, with worse overall survival, progression-free survival, objective response, and disease control rates. Clinical activity observed with 1L therapy with first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKIs is not permanent, and resistance inevitably develops in all cases, supporting the importance of overall treatment planning. The introduction of the 3G EGFR-TKI, osimertinib, provides an opportunity to overcome T790M-mediated resistance to 1G, and 2G EGFR-TKIs. Additionally, with the use of osimertinib, fewer T790M mutations are being detected as T790M is not a reported resistance mechanism to 3G EGFR-TKIs. However, there are currently no approved targeted therapies after 3G EGFR-TKIs. In order to further improve patient outcomes, there is a need to explore additional options for the overall treatment strategy for patients, including 1L and beyond. Combination of vascular endothelial growth factor (VEGF) inhibitors and EGFR-TKIs or chemotherapy and EGFR-TKIs may be a potential therapeutic approach in the 1L setting. This review discusses current treatment options for mNSCLC with activating EGFR mutations based on tumor, patient, and treatment characteristics and how an overall treatment plan may be developed

Surgical approach to adrenal ganglioneuroma: Case report and literature review

Objective: Ganglioneuroma (GN) is a benign tumor with a slow growth that can originate from any paravertebral sympathetic plexus. It is usually asymptomatic or with nonspecific symptoms. TC and RM scan are helpful to study GN. It is usually represented by an ovalshaped retroperitoneal mass or, in case of adrenal impairment, by low radiologic contrast media attenuation. Surgical treatment is mandatory. Literature shows how the laparoscopic approach is the most used, especially in lesions that are 6 cm or smaller. Our purpose is to describe our experience on an incidental adrenal GN of about 5 cm treated by the laparoscopic transperitoneal approach. Materials and methods: A 33-year-old male had ultrasound occasional finding of an about 4 cm adrenal mass. TC and RM scan identified a retroperitoneal mass (max diameter 48 mm). The lesion was removed with a transperitoneal laparoscopic approach. Results: No intraoperative or postoperative complications occurred. The patient was discharged 3 days after surgery. Conclusions: Up to the present laparoscopic surgery is the best approach for GN treatment

skin flap squamous cell carcinoma developed after urethroplasty

Objectives: To describe our experience in diagnosis and treatment of urethral carcinoma following urethroplasty with a Orandi penile skin flap. Material and methods: Our patient underwent to Orandi penile skin flap urethroplasty then developed a urethral epidermoid carcinoma on the flap approximately 15 years later. We treated this case with a partial penectomy surgery and perineostomy. Surgery was followed by chemotherapy with cisplatin and 5-fluorouracil. The progression of the disease led to a salvage surgery of total penectomy and asportation of testicles and scrotum.Results: Despite the success of the surgery, the disease progressed and three months after the last surgical operation the patient died. Conclusions: Urethral carcinoma on skin flap is a rare complication of the urethroplasty surgery but with severe consequences, so we recommend to undertake a long-term urological follow up in patients undergone such kind of surgery

Defects in III-N LEDs: experimental identification and impact on electro-optical characteristics

III-N light-emitting-diodes (LEDs) are subject of intense investigations, thanks to their high efficiency and great reliability. The quality of the semiconductor material has a significant impact on the electro-optical performance of LEDs: for this reason, a detailed characterization of defect properties and the modeling of the impact of defects on device performance are of fundamental importance. This presentation addresses this issue, by discussing a set of recent case studies on the topic; specifically, we focus on the experimental characterization of defects, and on the modeling of their impact on the electro-optical characteristics of the devices

Low-protein diets for chronic kidney disease patients: The Italian experience

open20Nutritional treatment has always represented a major feature of CKD management. Over the decades, the use of nutritional treatment in CKD patients has been marked by several goals. The first of these include the attainment of metabolic and fluid control together with the prevention and correction of signs, symptoms and complications of advanced CKD. The aim of this first stage is the prevention of malnutrition and a delay in the commencement of dialysis. Subsequently, nutritional manipulations have also been applied in association with other therapeutic interventions in an attempt to control several cardiovascular risk factors associated with CKD and to improve the patient's overall outcome. Over time and in reference to multiple aims, the modalities of nutritional treatment have been focused not only on protein intake but also on other nutrients.openBellizzi, Vincenzo; Cupisti, Adamasco; Locatelli, Francesco; Bolasco, Piergiorgio; Brunori, Giuliano; Cancarini, Giovanni; Caria, Stefania; De Nicola, Luca; Di Iorio, Biagio R; Di Micco, Lucia; Fiaccadori, Enrico; Garibotto, Giacomo; Mandreoli, Marcora; Minutolo, Roberto; Oldrizzi, Lamberto; Piccoli, Giorgina B; Quintaliani, Giuseppe; Santoro, Domenico; Torraca, Serena; Viola, Battista FBellizzi, Vincenzo; Cupisti, Adamasco; Locatelli, Francesco; Bolasco, Piergiorgio; Brunori, Giuliano; Cancarini, Giovanni; Caria, Stefania; De Nicola, Luca; Di Iorio, Biagio R; Di Micco, Lucia; Fiaccadori, Enrico; Garibotto, Giacomo; Mandreoli, Marcora; Minutolo, Roberto; Oldrizzi, Lamberto; Piccoli, Giorgina B; Quintaliani, Giuseppe; Santoro, Domenico; Torraca, Serena; Viola, Battista F

Notulae to the Italian alien vascular flora: 11

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, exclusions, and status changes for Italy or for Italian administrative regions. Nomenclatural and distribution updates published elsewhere are provided as Suppl. material 1