Jensenholt4261

A mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, named GSB-106, was designed and synthesized in our scientific group. The compound activated TrkB, MAPK/ERK, PI3K/AKT, and PLCγ in in vitro experiments. In vivo experiments with rodents revealed its antidepressant-like activity in the forced swim and the tail suspension tests at the dose range of 0.1-5.0 mg/kg (i.p., p.o.). However, GSB-106 was not studied in depression models modulating major depression in humans. In the present study, the GSB-106 antidepressant-like activity was revealed in mice at the depression model induced by 28-day social defeat stress with 21-days oral administration (0.1 mg/kg) after stress. At the same time, GSB-106 restored reduced locomotor activity and completely eliminated the anhedonia manifestations. The compound also restored reduced levels of synaptophysin and CREB in the hippocampus. In addition, the Trk receptor antagonist K252A, and the PLC inhibitor U73122, were found to completely block the antidepressant-like activity of GSB-106 in the forced swimming test in mice. Thus, the present results demonstrate the dipeptide BDNF mimetic GSB-106 reversed depressive-like behavior and restored hippocampal neuroplasticity in a rodent depression model. These effects of GSB-106 are probably regulated by TrkB signaling.Chronic kidney disease (CKD) is one of the most common chronic non-communicable degenerative diseases and it represents an important risk factor for cardiovascular morbidity and mortality. The Mediterranean diet, in which extra virgin olive oil (EVOO) is the main source of vegetal fats, represents a nutritional-diet regimen that is useful for the treatment of CKD and its comorbidities. Calcitriol chemical structure We tested two different EVOOs, characterized by a high (Synergy) and medium (Luxolio) content of minor polar compounds (MPCs), detected by HPLC-DAD-MS analysis, in 40 nephropathic patients, at a dose of 40 mL/day for 9 weeks. We evaluated the effects of these two EVOOs on renal function, body composition, oxidative stress, and inflammatory state, after 9 weeks of EVOOs consumption (T1) and after 2 months of wash-out (T2). We observed an improvement of renal function biomarkers (estimated-glomerular filtration rate, albuminuria, azotemia, uric acid), lipid profile, oxidative stress, inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein) and in body composition at T1. These healthy effects were greater and persisted over time after the wash-out period in Synergy patients. The high MPC EVOO content seems to exert an antioxidant and anti-inflammatory effect in nephropathic patients and these protective actions are maintained over time.Lack of cereal nutritional water productivity (NWP) information disadvantages linkages of nutrition to water-food nexus as staple food crops in Sub-Saharan Africa (SSA). This study determined the suitability of sorghum (Sorghum bicolor L. Moench) genotypes to alleviate protein, Zn and Fe deficiency under water-scarce dryland conditions through evaluation of NWP. Sorghum genotypes (Macia, Ujiba, PAN8816, IsiZulu) NWP was quantified from three planting seasons for various sorghum seed nutrients under dryland semi-arid conditions. Seasons by genotypes interaction highly and significantly affected NWPStarch, Ca, Cu, Fe, and significantly affected NWPMg, K, Na, P, Zn. Genotypic variations highly and significantly affected sorghum NWPProtein, Mn. Macia exhibited statistically superior NWPprotein (13.2-14.6 kg·m-3) and NWPZn (2.0-2.6 g·m-3) compared to other tested genotypes, while Macia NWPFe (2.6-2.7 g·m-3) was considerably inferior to that of Ujiba and IsiZulu landraces under increased water scarcity. Excellent overall NWPprotein, Fe and Zn under water scarcity make Macia a well-rounded genotype suitable to alleviating food and nutritional insecurity challenges in semi-arid SSA; however, landraces are viable alternatives with limited NWPprotein and Zn penalty under water-limited conditions. These results underline genotype selection as a vital tool in improving "nutrition per drop" in semi-arid regions.The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy.This study aimed to discover concurrences of adverse drug reactions (ADRs) and derive models of the most frequent items of ADRs based on the SIDER database, which included 1430 marketed drugs and 5868 ADRs. First, common ADRs of organic drugs were manually reclassified according to side effects in the human system and followed by an association rule analysis, which found ADRs of digestive and nervous systems often occurred at the same time with a good association rule. Then, three algorithms, linear discriminant analysis (LDA), support vector machine (SVM) and deep learning, were used to derive models of ADRs of digestive and nervous systems based on 497 organic monomer drugs and to identify key structural features in defining these ADRs. The statistical results indicated that these kinds of QSAR models were good tools for screening ADRs of digestive and nervous systems, which gave the ROC AUC values of 81.5%, 98.9%, 91.5%, 69.5%, 78.4% and 78.8%, respectively. Then, these models were applied to investigate ADRs of 1536 organic compounds with four phase and zero rule-of-five (RO5) violations from the ChEMBL database. Based on the consensus ADRs' predictions of models, 58.1% and 42.6% of compounds were predicted to cause these two ADRs, respectively, indicating the significance of initial assessment of ADRs in early drug discovery.The COVID-19 emergency has imposed distanced education and has interrupted most rehabilitation services. Adolescents with disabilities have been isolated, and the burden on their families has been exacerbated. A cross-sectional survey was administered to adolescents with disability and to parents of disabled children to describe their experience during lockdown and their concerns or expectations about rehabilitation. A sample of 53 adolescents and 239 parents completed the survey. Adolescents were ages 13-18 years old (45.3% female). Most parents were between 35 and 55 years old (84.9% female). While 53.6% of the parents reported no positive effects of the lockdown, 92.5% of the adolescents expressed favorable consequences. The increased time spent with family members was judged positively by 27.2% of parents and by 64.2% of adolescents. Concern for their child's disability was expressed by 47.3% of parents, while 73.6% of adolescents expressed concerns regarding the ban on meeting friends. In both groups, anxiety symptoms were correlated with the fear of contracting COVID-19 and with financial problems. Parents would have liked even more remote support from school and healthcare professionals, which was available for most participants. Thus, socioeconomic support, assistive technology and telerehabilitation strategies might help families with disabilities during a lockdown.Cognitive dysfunction affects the performance of Activities of Daily Living (ADL) and the quality of life of people with these deficits and their caregivers. To the knowledge of the authors, to date, there are few studies that focus on knowing the relationship between personal autonomy and deductive reasoning and/or categorization skills, which are necessary for the performance of the ADL. The aim of this study was to explore the relationships between ADL and categorization skills in older people. The study included 51 participants 31 patients with cognitive impairment and 20 without cognitive impairment. Two tests were administered to assess cognitive functions (1) the Montreal Cognitive Assessment (MoCA); and (2) the digital version of Riska Object Classification test (ROC-d). In addition, the Routine Tasks Inventory-2 (RTI-2) was applied to determine the level of independence in activities of daily living. People with cognitive impairment performed poorly in categorization tasks with unstructured information (p = 0.006). Also, the results found a high correlation between cognitive functioning and the performance of ADLs (Physical ADL r = 0.798; p less then 0.001; Instrumental ADL r = 0.740; p less then 0.001), a moderate correlation between Physical ADLs and categorization skills (unstructured ROC-d r = 0.547; p less then 0.001; structured ROC-d r = 0.586; p less then 0.001) and Instrumental ADLs and categorization skills in older people (unstructured ROC-d r = 0.510; p less then 0.001; structured ROC-d r = 0.463; p less then 0.001). The ROC-d allows the assessment of categorization skills to be quick and easy, facilitating the assessment process by OT, as well as the accuracy of the data obtained.

Due to the rarity of osteosarcoma and limited indications for radiotherapy (RT), data on RT for this tumor are scarce. This study aimed to investigate the utilization of RT for osteosarcomas in the recent 20 years and to identify factors related to patients' response to radiation.

We performed a retrospective analysis of patients irradiated for osteosarcoma treatment. We planned to assess differences in the utilization of RT between the periods of 2000-2010 and 2011-2020, identify the risk factors associated with local progression (LP), determine whether RT-related parameters are associated with LP, and calculate patients' survival.

A total of 126 patients with osteosarcoma who received 181 RT treatments were identified. We found a difference in RT techniques between RT performed in the years 2000-2010 and that performed in the years 2011-2020. LP was observed after 37 (20.4%) RT treatments. Intent of RT, distant metastases, and concomitant systemic treatment affected the risk of LP. Five-year overall survival was 33% (95% confidence interval (26%-43%)).