Among gynaecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumour occurrence, growth and development. Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcription factor, playing an important role in protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) activate NRF2 signalling, inducing the expression of antioxidant enzymes, such as haem oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), that protect cells against oxidative stress. However, NRF2 activation in cancer cells is responsible for the development of chemoresistance, inactivating drug-mediated oxidative stress that normally leads to cancer cells’ death. In this review, we report evidence from the literature describing the effect of NRF2 on ovarian cancer, with a focus on its function in drug resistance, NRF2 natural and synthetic modulators and its protective function in normal ovarian preservation.

Prophylaxis is safe in cirrhotic patients without esophageal varices; the real need for prophylaxis should be better assessed.

Total knee modular megaprosthesis or osteochondral allograft are used to preserve joint movement in bone tumours of the proximal tibia. The aim of this study was to compare two groups of patients with total knee modular megaprosthesis and osteochondral allograft through an objective analysis. Eighteen patients, ten treated with prosthesis (TKR group) and eight with osteochondral allografts (AL group), were included in the study. X-ray, muscular strength measurements, and studies of gait analysis including electromyography (EMG) were used to compare functional results of patients. In the TKR group a higher incidence of knee extension lag was found. While the TKR group had a prevalent knee stiff/hyperextension pattern with reduced rectus femoris activity, the AL group had a higher percentage of normal knee pattern. Knee extensor muscular strength was reduced in the TKR group. TKR functional performance during gait is in most cases abnormal, consistent with the weakness of the extensor apparatus and knee extension lag. Although a greater rate of normal walking was found in the AL group, problems related to a short patellar tendon, knee instability, and joint mismatching were considered to be responsible for abnormal knee kinematics. An allograft, when optimal reconstruction is performed, gives better functional results.Résumé Les prothèses totales massives et les allogreffes ostéochondrales sont utilisées pour préserver le mouvement articulaire dans les tumeurs du tibia proximal. Le but de cette étude était de comparer 2 groupes de patients ayant reçus ces traitements. 18 patients étaient inclus dans l'étude, 10 traités par prothèse (groupe TKR) et 8 par allogreffe ostéochondrale (groupe AL). Les radiographies, la mesure de la force musculaire, l'étude de la boiterie incluant l'EMG étaient utilisées pour comparer les résultats fonctionnels. Dans le groupe TKR une plus grande incidence de perte d'extension était notée. Tandis que le groupe TKR avait une réduction de l'activité du Rectus fémorus , le groupe AL avait un plus grand pourcentage de fonction normale. La force musculaire des extenseurs était réduite dans le groupe TKR. La performance fonctionnelle durant la marche des TKR étaient la plupart du temps anormal avec faiblesse de l'appareil extenseur et perte d'extension. Bien qu'un taux plus élevé de marche normale était trouvé dans le groupe AL, les problèmes dû à un tendon rotulien court, une instabilité articulaire et à une articulation mal adaptée étaient supposés responsable d'une cinématique anormale du genou. L'allogreffe, quand une reconstruction optimale était réalisée donnait un meolleur résultat fonctionnel.

Background: Synthetic benzimidazole opioids (BOs) are highly potent m-opioid receptor agonists with heroin-like effects. Isotonitazene was first available in 2019 in the drug market, although new analogs have multiplied recently. The authors aimed to identify BO use trends and gather toxicological data from BO-related cases to assist in clinical and forensic investigations.Methods: A systematic literature search was conducted according to the PRISMA guidelines. PubMed and Scopus databases were accessed in October 2021 to identify scientific reports of BO-related intoxication and fatalities. Publication dates, case descriptions, symptoms, autopsy findings, and concentrations of BOs and metabolites in biological matrices were compiled.Results: Data from 8 case reports with 93 fatalities involving isotonitazene (n = 65), metonitazene (n = 20), etonitazepyne (Npyrrolidino etonitazene) (n = 8), flunitazene (n = 4), and/or butonitazene (n = 1), and 1 acute intoxication involving etonitazepyne were collected. Autopsy findings included pulmonary congestion/high lung weight (66%), cardiomegaly/high cardiac weight (39%), cerebral edema (22%), gastric contents in the airways (22%), and organ congestion (22%). Median peripheral blood concentrations were 1.7 ng/mL for isotonitazene (0.4-9.5 ng/mL, n = 13), 5.4 ng/mL for metonitazene (0.52-33 ng/mL, n = 17), 5.4 ng/mL for etonitazepyne (2.4-8.3 ng/mL, n = 2), 1.3 ng/mL for flunitazene (0.58-2.1 ng/mL, n = 2), and 3.2 ng/mL for butonitazene (n = 1). Central nervous system depressants were almost always coadministered.Conclusions: Isotonitazene was predominant in cases from 2019 to mid-2020 and was replaced by metonitazene after scheduling in the United States. Typical findings on opioid overdoses have been reported. Peripheral blood concentrations were consistent with a potency similar to that of fentanyl. These results must be interpreted carefully, considering the scarcity of reports on BO-related cases and drug co-exposures.

According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances’ cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.