Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives

Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and post-operative chemotherapy. In order to ameliorate survival rates of patients, new therapeutic approaches have been evaluated, mainly immunotherapy with antibody-drug conjugates or immunoconjugates. These molecules consist of a carrier (frequently an antibody) joined by a linker to a toxic moiety (drug, radionuclide, or toxin). Although several clinical trials with immunoconjugates have been conducted, mainly in hematological tumors, their potential as therapeutic agents is relatively under-explored in many types of cancer. In this review, we report the immunoconjugates directed against OS surface antigens, considering the in vitro and in vivo studies. To date, several attempts have been made in preclinical settings, reporting encouraging results and demonstrating the validity of the idea. The clinical experience with glembatumumab vedotin may provide new insights into the real efficacy of antibody-drug conjugates for OS therapy, possibly giving more information about patient selection. Moreover, new opportunities could arise from the ongoing clinical trials in OS patients with unconjugated antibodies that could represent future candidates as carrier moieties of immunoconjugates

A Systemic and Severe Infection via Cytomegalovirus and Other Herpesviruses in a Young Apparently Immunocompetent Patient: A Case Report

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Integrated environmental analysis of urban waste separate collection in the Sorrento peninsula, in Italy

The main aim of this work was to study the kerbside collection system of two municipalities in the Sorrento peninsula (in Italy) with an integrated approach based on the three pillars of sustainability: society, environment and economy. The studied municipality are Sorrento (16,745 inhabitants, 1,681 inhabitants/km²) and Piano di Sorrento (13,159 inhabitants, 1,793 inhabitants/km2). Piano di Sorrento and especially Sorrento are tourist towns and this obviously has an impact on the quantity and quality of urban waste. In 2014, the percentage of separate collection was 63.3% in Piano di Sorrento with a per capita production of 465.7 kg/inhabitant/year, and 63.8% in Sorrento with 775 kg/inhabitant/day. In every municipality, there is a separate collection centre (SCC). In the SCC, the citizens can deliver the recyclables from urban waste obtaining economic benefits similarly to the system described in De Feo and Polito (2015). The sociological analysis was developed by means of a structured questionnaire similar to that developed by De Feo and Polito (2015). The economic analysis was conducted in the light of the Extended Producer Responsibility (EPR) system, evaluating the money recovery from the recyclable materials theoretically contained in the residual waste. The analysis was carried out considering three real scenarios: (1) 2000, without separate collection; (2) 2008, when the Campania region of Southern Italy was suffering serious problems with the management of urban waste because the region did not have enough waste management facilities; (3) 2014, when there was an effective kerbside collection system in the two municipalities. The environmental analysis was performed for scenarios (1), (2) and (3) applying the Life Cycle Assessment (LCA) approach to the urban waste management, internal collection and external transport systems. As shown in Figure 1, in 2014, the increasing percentages of separate collection allowed to avoid the production of environmental impacts, with greater benefits for the citizens of Piano di Sorrento. On the other hand, for Sorrento it was calculated the number of theoretical additional touristic bus/day in the case of a “Zero Waste” management of the hotels in terms of avoided production of equivalent CO2. The result was obtained as the ratio between the difference of the impact produced by the hotels all operated in a normal way and the hotels all managed with a Zero Waste approach, and the impact of a single bus (as a function of the distance). Please click Additional Files below to see the full abstract

Determinación de parámetros de transporte de calor y masa en materiales constructivos

La norma Iram N° 11.625/91 considera la condensación del vapor de agua transportado en los cerramientos edilicios, por el gradiente de presión de vapor. Frente a las condiciones climatológicas de nuestra región en época invernal, puede ocurrir el congelamiento del agua ocluida proveniente de la condensación, situación no contemplada en la norma. Además, es necesario la determinación de los parámetros de transporte de calor y masa correspondientes a materiales de construcción de origen local. El modelo experimental permite determinar las conductividades térmicas de dichos materiales, secos y húmedos, la variación de las mismas con diferentes porcentajes de humedad y las permeabilidades al pasaje de vapor de agua. Estas mediciones son necesarias para el diseño de un modelo de predicción del riesgo de congelamiento. Describimos el equipo experimental y adjuntamos las tablas correspondientes a las determinaciones.Facultad de Arquitectura y Urbanism

Evaluation of Orexin-A serum levels in karate athletes cohort

The lateral hypothalamus products various neuropeptides, among of these the Orexin-A (hypocretin-1) is a protein that regulates numerous physiological and behavioural processes involving in energy balance and metabolic status, physical activity, blood glucose levels, and food intake. Many data literature reported that the production of Orexin-A increases following regular and structured physical activity. Indeed, it improves energy metabolism and insulin sensitivity, and also modulate energy expenditure and thermogenesis. The higher Orexin-A tone is an endogenous factor that predicts physical activity, improving BMI and the energy expenditure aspect. It is well known that physical activity has positive effects on health and body weight, it improves cognitive performance increasing Orexin-A levels. Given these evidences, the aim of this study is evaluated Orexin-A serum levels in a cohort of karate athletes. Fort these reasons, were recruited 10 young karate athletes and 10 matched non-athletes as control. We evaluated biochemical and anthropometric parameters, and Orexin-A serum levels through ELISA-test. Our results showed that there is a statistical difference between karate athletes and non-athletes in BMI and in biochemical parameters such as glycaemic and lipid profile. Interestingly, Orexin-A serum levels are statistical higher in karate athletes compared to non- athletes. The differences between athlete and non-athletes in this study could be attributed to a better training-related hypothalamic activity in karate athletes. In addition, these evidences indicate that the physical activity has beneficial effects not only on anthropometric and biochemical parameters but also on orexin-A levels, and then on central nervous system

Physical activity as protective factor against COVID-19 disease

The Coronavirus Pandemic has forced millions of people around the world to look at home. This resulted, as a consequence, in a remodelling of the lifestyle; in this scenario the correct nutrition combined with regular physical activity becomes fundamental for health. Although the sedentary lifestyle of a few weeks involves risks such as lowering the immune system, it favours overweight and obesity, high blood pressure, metabolic disorders, depression and anxiety, and in some subjects they react to the risk of onset of cardiovascular disease, diabetes and other diseases. The importance of healthy lifestyle is crucial to prevent also viral infection. Indeed, as reported by many data literature, during lung infections, IL-6 and TNF-a create the pathway between adipose tissue and lung system demonstrating the important involvement of adipose tissue in lung diseases. In obese condition, adipose tissue endocrine function is altered. There is an imbalance in the production of pro-inflammatory cytokines such as IL-6 and TNF-a and anti-inflammatory mediators such as IL-10. In the light of these evidences, the immune response is influenced by nutritional status and by physical activity which are able to reduce pro-inflammatory mediators and increase anti-inflammatory mediators such as IL-10 . In addition, the power of viral infection is influenced by host predisposition. For these reasons, a correct lifestyle, and physical activity are a valid strategy in the prevention and treatment of not metabolic diseases also of inflammatory diseases

Autism spectrum disorder and physical activity

Autism is a common developmental disorder characterized by difficulties with speech and behaviours, such as lack of social abilities and repetitive behaviours. Some studies have shown that after the intervention of physical activity, all of the social interaction ability, communication ability, stereotyped behaviour and sports skills of children and adolescents with autism have been improved, which can reduce the degree of autism. The prevalence of autism spectrum disorder (ASD) has increased dramatically and is currently estimated at 1 in 68 children. ASD is defined by two symptom dimensions including social impairments and circumscribed and repetitive behaviours and interests (American Psychiatric Association). One subgroup that has increased is those with ASD without intellectual disability who currently comprise 68% of those diagnosed. Current guidelines recommend that youth engage in ≥ 60 minutes of Physical Activity daily, with the majority being moderate-to-vigorous, and muscle strengthening activities ≥ 3 days per week. Despite the significant need, few exercise programs have been developed or adapted for children with ASD, and there is a lack of evidence-based exercise treatments. Recommendations for improving exercise intervention studies in ASD include testing of treatments in function-ally-homogeneous (narrower) subgroups with ASD using larger well-characterized samples. This is necessary as children with ASD have different tolerances for activities/tasks and functional heterogeneity will likely lead to variable treatment responsiveness. Additionally, group-based treatments will be more applicable for children with ASD without intellectual disability

Swine cortical and cancellous bone: histomorphometric and densitometric characterisation

Introduction: Swine bone morphology, composition and remodelling are similar to humans’, therefore they are considered good models in bone-related research. They have been used for several studies involving bone growth, bone and cartilage fractures and femoral head osteonecrosis. Nevertheless, the literature about pig normal bone features is incomplete. This work aims to fill the literature gaps on the microarchitecture and Bone Mineral Density (BMD) of swine femoral diaphysis and distal epiphysis and tibial plateau and diaphysis.Materials and methods: Five hind limbs were collected from slaughtered 80-100 kg pigs. Microscopic analysis of cortical and cancellous bone from middle/distal femur and proximal/middle tibia was performed to determine basic histomorphometric parameters at different sites. Dual-energy X-Rays Absorptiometry was also employed to evaluate BMD. ANOVA and correlation between BMD, bone area (BA) and cortical thickness were performed.Results and discussion: Diaphyseal cortical bone was mostly plexiform both in the tibia and the femur; primary/secondary osteons without clear organization were also found. Mean values for bone area, bone perimeter, trabecular width, number and separation and BMD at different anatomical sites were defined. No significant difference was found for these values at different anatomical sites. BMD proved to be positively correlated with cortical thickness (r=0,80; p<0,01). Despite the small sample size, these results seem homogeneous. They could therefore represent reference values for normal bone parameters in pigs. Applied anatomy and regenerative medicine, in fact, demand very precise information about bone micromorphology, composition and density to provide reliable indication in bone substitutes building. Moreover, since the interpretation of bone abnormalities is based on mastering normal bone characteristics, the definition of reference parameters is mandatory to avoid misinterpretation and allow comparative evaluation.Conclusion: The results of this study, although preliminary, may be considered a dependable starting point for the definition of normal bone features in pigs

A comparison between overweight cutoff points for detection of high blood pressure in adolescents

OBJETIVOS: Avaliar a acurácia de três pontos de corte na determinação da pressão arterial elevada em adolescentes, dada a forte relação entre o excesso de peso e valores elevados de pressão arterial. MÉTODOS: Participaram do estudo 1.021 adolescentes de ambos os sexos, selecionados de maneira aleatória nas escolas públicas e particulares de Londrina (PR). O peso corporal foi aferido por meio de balança digital, e a estatura, por um estadiômetro portátil com extensão máxima de 2 metros. A pressão arterial foi avaliada através de um aparelho automático. A capacidade do índice de massa corporal de detectar a pressão arterial elevada foi averiguada por meio da curva ROC e seus parâmetros (sensibilidade, especificidade e área sob a curva). RESULTADOS: Os pontos de corte da proposta nacional apresentaram maior acurácia (masculino: 0,636±0,038; feminino: 0,585±0,043) quando comparados aos pontos de corte das propostas internacional (masculino: 0,594±0,040; feminino: 0,570±0,044) e norte-americana (masculino: 0,612±0,039; feminino: 0,578±0,044). CONCLUSÃO: A proposta nacional foi a que apresentou melhor acurácia na indicação de valores elevados de pressão arterial.OBJECTIVES: To evaluate the accuracy of three different cutoff points for the detection of high blood pressure in adolescents, given the strong relationship between overweight and high blood pressure levels. METHODS: A total of 1,021 adolescents of both sexes were enrolled in the study, selected at random from public and private schools in Londrina, Brazil. Their body weight was measured using a digital balance, and their height with a portable stadiometer with a maximum extension of 2 meters. Arterial blood pressure was measured using an automatic apparatus. The capacity of body mass index to detect high blood pressure was gauged using ROC curves and their parameters (sensitivity, specificity, and area under the curve). RESULTS: The cutoff points proposed in a Brazilian standard exhibited greater accuracy (males: 0.636±0.038; females: 0.585±0.043) than the cutoff points proposed in an international (males: 0.594±0.040; females: 0.570±0.044) and a North-American standard (males: 0.612±0.039; females: 0.578±0.044). CONCLUSIONS: The Brazilian proposal offered greatest accuracy for indicating high blood pressure levels

Effects of Tibetan Music on Neuroendocrine and Autonomic Functions in Patients Waiting for Surgery: A Randomized, Controlled Study

Background. The aim of this study was to investigate the effects of listening to Tibetan music on anxiety and endocrine, autonomic, cognitive responses in patients waiting for urologic surgery. Methods. Sixty patients waiting for surgery were enrolled to the study. They were randomized in music (M) and control (C) groups. The M group listened to a low-frequency Tibetan music for 30 min (T0–T30) through headphones, and the C group wore headphones with no sound. The State Trait Anxiety Inventory Questionnaire (STAI) Y-1 was administered at T0 and T30. Normalized low (LFnu) and high frequencies (HFnu) of heart rate variability, LF/HF ratio, and galvanic skin response (GRS) data were analyzed at T0, T10, T20, T30, and T35. The salivary α-amylase (sAA) samples were collected at T0, T35, and T45. Results. In the M group, the STAI Y-1 score decreased at T30 versus baseline p<0.001, sAA levels decreased at T35 versus T0p=0.004, and GSR remained unchanged. In the C group, the STAI Y-1 score remained unchanged, sAA level increased at T35 versus T0p<0.001, and GSR slightly increased at T35 versus baseline p=0.359. LFnu was lower, and HFnu was significantly higher (T10–T30) in M versus C group. Mean LF/HF ratio slightly reduced in the M group. Conclusions. Our results suggest that preoperative listening to relaxing Tibetan music might be a useful strategy to manage preoperative anxiety