Hip fracture. Preliminary results supporting significative correlations between the psychological wellbeing of patients and their relative caregivers

Background and aim. Hip fracture is one of the major causes of loss of self-sufficiency in older patients. The associated caregiving rehabilitation task often falls to the lot of a member of the patient’s family. Our study aims at assessing the relationship between the psychological well-being of patients with hip fracture and their caregivers. Methods. The study was carried-out on 53 elderly patients with hip fracture and their primary caregivers. The Mini Mental State Examination (patient), Activities of Daily Living (patient), Instrumental Activities of Daily Living (patient), Geriatric Depression Scale (patient), Psychological General Well-Being Index (patient/caregiver) and the Caregiver Burden Inventory (caregiver) were administered to each participant. Results. The results revealed significant correlations between stress levels and the psychological well-being of hip-fracture patients and relative caregivers. In particular, the Caregiver Burden Inventory’s total score was negatively related to the patient’s Psychological General Well-Being Index score (p < 0.05) and with Anxiety (p < 0.05), Depressed Mood (p < 0.01), Positive Well-being (p < 0.05) and General Health (p < 0.05) subscale scores, as well as with the patient’s Activities of Daily Living (p < 0.05) score. Patients’ Psychological General Well-Being Index scores were related to the caregivers’ General Health subscale (p < 0.01), and negatively related to Caregiver Burden Inventory Time Dependence (p < 0.05) and Social Burden (p < 0.05) subscales, as well as with the Geriatric Depression Scale score (p < 0.05). Conclusion. A mutual relationship seems to exist between a patient’s psychological well-being and his/her caregiver’s burden. These findings highlight the importance of a bio-psychosocial approach to both patients and caregivers

Development of biologic devices for mesothelin immunotargeting

La mesotelina \ue8 una glicoproteina di superfice cellulare sintetizzata a partire da un precursore di 71 kDa che viene processato in un frammento di 40 kDa legato alla membrana ed un fattore solubile potenziante i megacariociti di 31 KDa. La mesotelina rappresenta un promettente biomarcatore tumorale; in condizioni fisiologiche \ue8 espressa dalle cellule mesoteliali delle sierose dell\u2019organismo (pleura, pericardio e peritoneo) mentre \ue8 overespressa sulla superficie cellulare di diversi istotipi tumorali tra cui: il mesotelioma maligno, il carcinoma ovarico, pancreatico e polmonare. La sua funzione \ue8 sconosciuta ma recentemente \ue8 stato ipotizzato un suo ruolo nei meccanismi di adesione cellulare attraverso il legame all\u2019antigene tumorale CA125. La limitata espressione della mesotelina a livello dei tessuti fisiologici e, di contro, l\u2019elevata espressione in molti tumori, rendono questo antigene un possibile target nella immunoterapia anti-tumorale. Il presente lavoro descrive la generazione di un nuovo anticorpo monoclonale anti-mesotelina ottenuto mediante la tecnologia degli ibridomi e la caratterizzazione delle sue propriet\ue0 di riconoscimento. Tale anticorpo monoclonale \ue8 stato testato per valutare un suo potenziale utilizzo terapeutico e diagnostico. L\u2019anticorpo anti-mesotelina ha dimostrato, in analisi condotte mediante citofluorimetria, una notevole specificit\ue0, essendo in grado di riconoscere cellule che esprimono l\u2019antigene mesotelina costitutivamente (OVCAR-3) e per trasfezione (HEK293-mesotelina); allo stesso tempo l\u2019anticorpo ottenuto non possiede la capacit\ue0 di legare cellule mesotelina negative. La specificit\ue0 di riconoscimento in vitro \ue8 paragonabile all\u2019anticorpo monoclonale commerciale K1 da noi utilizzato come controllo positivo. Studi di binding, inoltre, hanno permesso di evidenziare la migliore affinit\ue0 del nostro anticorpo rispetto all\u2019anticorpo monoclonale commerciale K1. Basandoci su questi dati abbiamo sviluppato uno immunotossina chimica con le capacit\ue0 di riconoscimento del nostro anticorpo e l\u2019attivita citotossica della ricina (una potente tossina appartenente alla famiglia delle proteine inattivanti i ribosomi) con lo scopo di poter utilizzare tale costrutto nella immunoterapia passiva di tumori overesprimenti la mesotelina. Le frazioni raccolte e purificate dell\u2019immunotossina, ottenute mediante la produzione di un ponte disolfuro tra l\u2019anticorpo monoclonale e la ricina, risultano capaci di inibire del 50% la proliferazione cellulare (IC50). Tale attivit\ue0 citotossica si manifesta su cellule mesotelina positive ad una concentrazione di 0,03 nM e 0,09 nM rispettivamente a 36 h e 72 h di incubazione. Inoltre il nostro costrutto dimostra una elevata specificit\ue0 di riconoscimento in quanto non sono stati raggiunti valori di IC50 su cellule mesotelina-negative anche dopo aggiunta di concentrazioni pari o superiori a 78 nM dell\u2019immunotossina. Si \ue8 infine osservato che l\u2019attivit\ue0 citotossica di una concentrazione pari a 0,03 nM dell\u2019immunotossina \ue8 completamente neutralizzata dalla contemporanea aggiunta, nel terreno di coltura, dell\u2019 anticorpo anti-mesotelina da noi generato ad una concentrazione 1000 volte maggiore rispetto a quella dell\u2019immunotossina. Questo ultimo dato supporta i precedenti ottenuti potenziando l\u2019evidenza di una attivit\ue0 citotossica specifica e anticorpo mediata da parte della nostra immunotossina chimica.BACKGROUND: Mesothelin is a tumor differentiation antigen (Ag) that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is, however, highly expressed in several human cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer immunotherapy. RESULTS: In this study we have developed a monoclonal antibody (mAb) that is specific for the Ag mesothelin. It was produced by hybridomas technologies and we have performed Fluorescence Activated Cell Sorting (FACS) analysis to evaluate the specificity and affinity of this antibody for the Ag of interest. The mAb binds mesothelin-positive cell lines expressing the Ag constitutively (OVCAR-3) and transfected cells (HEK293-mesothelin). The same mAb not recognizes mesothelin-negative cell lines demonstrating an high specificity in vitro. Binding studies have demonstrated that our mAb has a better affinity with respect to mAb K1, a commercially available anti-mesothelin mAb. Our anti-mesothelin mAb was chemically linked to ricin A chain (RTA) toxin obtaining a powerful immunodelivered drug (immunotoxin, IT) with specific cytotoxic activity on mesothelin positive cells; in a cytotoxic assay on HEK293-mesothelin transfected cells the anti-mesothelin mAb-RTA IT shows an IC50 of 0.03 nM and 0,09 nM after 36 hrs and 72 hrs of incubation respectively; no cytotoxic activity was observed against mock-not transfected one and other mesothelin negative cells. As a further proof of specificity we observed that the cytotoxic activity of 0,03 nM of the above-mentionated IT on HEK293-mesothelin cells, is fully prevented by addition of whole molecule mesothelin-specific antibody at a concentration 1000 fold over IT. CONCLUSION: Our mAb holds great potential to be used as a research reagent and diagnostic tool in research laboratories and in the clinics because of its high quality and versatility. This antibody is also a strong candidate to be investigated for further in vivo passive immunotherapy studies. Moreover, the discovered of this new mAb anti-mesothelin enable us to develop in vivo diagnostic approaches using radionuclide, fluorescence trackers or nanoparticles. Its conjugation with therapeutic molecules allows a better distribution of the drug to the tumor sites; this ability increase the antitumor efficacy and reduce the specific toxicity at the same time

The Global Impact of the COVID-19 Pandemic on Individuals’ and Couples’ Sexuality

The COVID-19 pandemic and its related restrictions significantly impacted individuals' health, wellbeing, and security. Isolation, limitation of movement, social distancing, and forced cohabiting have had a strong influence on all areas of people's lives as well as on their sexuality. Investigating how the COVID-19 outbreak and its consequences impacted people's sexuality was the primary aim of this review. Particularly, we focused on: (1) the variables associated with the improvement or the deterioration of individuals' and couples' lives during the pandemic; (2) the use of sex as a coping strategy; (3) the impact of COVID-19 outbreak on LGBT people. Results have shown that the worsening of sexual life seems to be related to couples' conflict, emotions and psychological difficulties, being female, being single or away from the partner, being a health care worker, and having children. Moreover, a detrimental effect on sexuality was associated with stress, forced cohabitation, routine, anxiety and worry about the job and the pandemic, feeling partner distance, being unhappy with their partner, and lack of privacy. On the other hand, improvements in sexuality were associated with living happily with a partner, being happy and satisfied with a partner, feeling less stressed and more bored, having more free time, having fewer recreation opportunities, and having minor workload. During the pandemic, there was an increase in using sex toys, pornography consumption, masturbating, and trying sexual experimentations. Among LGBT people, an increase was found in the number of casual sexual partners potentially due to the perceived lower likelihood of transmission through sex. Moreover, the increase in sexual activity may have represented a coping strategy to quarantine-related distress

Properties of graphene-related materials controlling the thermal conductivity of their polymer nanocomposites

Different types of graphene-related materials (GRM) are industrially available and have been exploited for thermal conductivity enhancement in polymers. These include materials with very different features, in terms of thickness, lateral size and composition, especially concerning the oxygen to carbon ratio and the possible presence of surface functionalization. Due to the variability of GRM properties, the differences in polymer nanocomposites preparation methods and the microstructures obtained, a large scatter of thermal conductivity performance is found in literature. However, detailed correlations between GRM-based nanocomposites features, including nanoplatelets thickness and size, defectiveness, composition and dispersion, with their thermal conductivity remain mostly undefined. In the present paper, the thermal conductivity of GRM-based polymer nanocomposites, prepared by melt polymerization of cyclic polybutylene terephtalate oligomers and exploiting 13 different GRM grades, was investigated. The selected GRM, covering a wide range of specific surface area, size and defectiveness, secure a sound basis for the understanding of the effect of GRM properties on the thermal conductivity of their relevant polymer nanocomposites. Indeed, the obtained thermal conductivity appeares to depend on the interplay between the above GRM feature. In particular, the combination of low GRM defectiveness and high filler percolation density was found to maximize the thermal conductivity of nanocomposites

A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds' activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan

Aluminum modulation of proteolytic activities

The effect of aluminum ions on the activity of proteolyic activities, mainly serine proteases and calpains, has been examined. Aluminum affects the biological activity of proteolytic activities either through a direct effect on the enzyme molecule or through a deregulation of the control mechanisms acting on them. Binding of the ion, most likely results in molecular rearrangements affecting both the substrates binding site and the site involved in the recognition of macromolecular inhibitors. As whole, the data reported clearly indicate that aluminum significatively affects the intracellular protein turnover, most likely triggering catastrophic events for the cellular life. The physiopathological significance of these effects has been discussed, in particular for neurological disorders (the Alzheimer's disease included) where an imbalance of proteolytic as well as antiproteolytic systems appears a crucial event both for the formation of neuritic plaques and neurofibrillary tangles which are the major hallmarks of the disease. © 2002 Elsevier Science B.V. All rights reserved