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Background: Family or friend carers of people with cancer report high levels of depression, anxiety, caregiving strain, and unmet needs. Limited strategies for identification and management of distress have been established among cancer carers. This paper describes the protocol of two linked studies: Study 1a, a distress screening and stepped care pathway feasibility study and Study 1b, a hybrid implementation-effectiveness Randomised Controlled Trial (RCT) to assess the benefit of a comprehensive, carer-centred online Cognitive Behavioural Therapy (iCBT) program for carers with anxiety and depression., Methods: For Study 1a, 300 cancer carers will be screened for distress. Carers with low distress will be referred to publicly available carer resources. Carers scoring 4 and higher on the distress thermometer will complete depression and anxiety measures. Carers with high anxiety/depression will be recommended psychological therapy. Carers with mild/moderate anxiety and/or depression will be allocated to the Carers iCBT Program, evaluated via a RCT with waitlist control group (Study 1b). For Study 1b, intervention group carers will receive access to a 6-lesson self-directed online iCBT program. Waitlist-controls will access the intervention at 14 weeks. Intervention and control groups will complete baseline, 6 week, and 14 week self-report measures; controls will complete additional measures at 20 and 28 weeks. A sample size of n = 166 carers in the iCBT RCT is needed., Conclusions: If acceptable, feasible and effective, this pathway and iCBT intervention could offer a sustainable, scalable and low-cost approach to identifying and managing distress in carers, and potentially improving patient and carer outcomes., Trial Registration: Australian and New Zealand Clinical Trial Registry number: ACTRN12623001341617p., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Many oncology health professionals (HPs) report communicating with carers as complex; and receive limited carer-relevant training. We developed an online HP education program for supporting and managing carer involvement (eTRIO). We aimed to assess whether HPs' self-efficacy in carer communication, knowledge, and decision-making preferences improve following eTRIO. Satisfaction and implementation potential were assessed., Methods: This type 1 hybrid effectiveness-implementation study used a pre-post single arm intervention design. HPs completed baseline measures, the eTRIO online module, and measures at 1- and 12-weeks post-intervention. Measures included: self-efficacy in carer communication (13-items), applied knowledge (7-items), preference for carer involvement in decisions (1-item). Fifteen of participants completed feedback interviews which underwent thematic analysis. User analytics were collected and analysed., Results: Fifty-six HPs completed baseline measures, 42 completed post- and follow-up measures. At baseline mean self-efficacy score was 88. HPs showed a statistically significant increase in self-efficacy post-intervention (mean = 105.8, CI [12.99, 20.47]), maintained at 12-weeks (mean = 101.1, CI [8.00, 15.72]). There were no changes in knowledge or decision-making preferences. Program engagement and satisfaction were high, 86.7% participants rated eTRIO as very/extremely helpful., Conclusions and Practice Implications: eTRIO provided HPs with confidence to effectively engage with carers and manage complex situations such as family dominance. These gains are noteworthy, as conflict with families/carers contributes to HP burnout., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: People living with multimorbidity often rely on the support of informal family carers, yet challenges frequently arise when carers of people with multimorbidity (PwM) interact with health professionals (HPs) and healthcare systems. This study aimed to provide insights into the experiences and challenges involved in working with carers of PwM, from HPs' perspectives., Methods: Twenty-one HPs (11 doctors, 5 nurses and 5 allied health professionals) from varying specialities participated in semi-structured interviews. Interviews were transcribed and qualitatively analysed using thematic analysis., Results: Five themes were identified: carer involvement makes multimorbidity easier to manage, differing views on HP's responsibilities to carers, multimorbidity makes management harder for HPs, strategies to support carers of PwM, and multimorbidity is one aspect of complexity., Conclusions: HPs recognise unique needs of carers of PwM, yet perceive challenges addressing these needs and supporting this commonly overlooked group., Practice Implications: The unmet needs of carers of PwM that HPs identified in this study suggest pathways for future improvements and interventions, including HP education and training, and appropriate referral pathways for carers of PwM to access supportive services. Underpinning these findings is the need for greater recognition and respect for the critical work of family carers in healthcare., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In a previous work we have shown that exposure to aluminum (Al) chloride (AlCl3) enhanced the neurotoxicity of the amyloid beta(25-35) fragment (Abeta(25-35)) in neuroblastoma cells and affected the expression of Alzheimer's disease (AD)-related genes. Caffein, a compound endowed with beneficial effects against AD, exerts neuroprotection primarily through its antagonist activity on A2A adenosine receptors (A2AR), although it also inhibits A1Rs with similar potency. Still, studies on the specific involvement of these receptors in neuroprotection in a model of combined neurotoxicity (Abeta(25-35)+AlCl3) are missing. To address this issue, cultured SH-SY5Y cells exposed to Abeta(25-35)+AlCl3 were assessed for cell viability, morphology, intracellular ROS activity and expression of apoptosis-, stress- and AD-related proteins. To define the role of A1R and A2ARs, pretreatment with caffein, specific receptor antagonists (DPCPX or SCH58261) or siRNA-mediated gene knockdown were delivered. Results indicate that AlCl3 treatment exacerbated Abeta(25-35) toxicity, increased ROS production, lipid peroxidation, β-secretase-1 (BACE1) and amyloid precursor protein (APP). Interestingly, SCH58261 successfully prevented toxicity associated to Abeta(25-35) only, whereas pretreatment with both DPCPX and SCH58261 was required to fully avert Abeta(25-35)+AlCl3-induced damage, suggesting that A1Rs might also be critically involved in protection during combined toxicity. The effects of caffein were mimicked by both N-acetyl cysteine, an antioxidant, and desferrioxamine, likely acting through distinct mechanisms. Altogether, our data establish a novel protective function associated with A1R inhibition in the setting of combined Abeta(25-35)+AlCl3 neurotoxicity, and expand our current knowledge on the potential beneficial role of caffein to prevent AD progression in subjects environmentally exposed to aluminum., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Age-related cognitive decline is accompanied by an increase of neuronal apoptosis and a dysregulation of neuroplasticity-related molecules such as brain-derived neurotrophic factor and neurotoxic factors including beta amyloid (Aβ) peptide. Because it has been previously demonstrated that phosphodiesterase-5 inhibitors (PDE5-Is) protect against hippocampal synaptic dysfunction and memory deficits in mouse models of Alzheimer's disease and physiological aging, we investigated the effect of a treatment with the PDE5-I, sildenafil, on cell death, pro- and antiapoptotic molecules, and Aβ production. We demonstrated that chronic intraperitoneal injection of sildenafil (3 mg/kg for 3 weeks) decreased terminal deoxyuridine triphosphate nick end labeling-positive cells in the CA1 hippocampal area of 26-30-month-old mice, downregulating the proapoptotic proteins, caspase-3 and B-cell lymphoma 2-associated X, and increasing antiapoptotic molecules such as B-cell lymphoma protein-2 and brain-derived neurotrophic factor. Also, sildenafil reverted the shifting of amyloid precursor protein processing toward Aβ42 production and the increase of the Aβ42:Aβ40 ratio in aged mice. Our data suggest that PDE5-I might be beneficial to treat age-related detrimental features in a physiological mouse model of aging., (Copyright © 2014 Elsevier Inc. All rights reserved.)

DNA double strand breaks (DSB) are the gravest form of DNA damage in eukaryotic cells. Failure to detect DSB and activate appropriate DNA damage responses can cause genomic instability, leading to tumorigenesis and possibly accelerated aging. Phosphorylated histone H2AX (γH2AX) is used as a biomarker of cellular response to DSB and its potential for monitoring DNA damage and repair in human populations has been explored in this review. A systematic search was conducted in PubMed for articles, in English, on human studies reporting γH2AX as a biomarker of either DNA repair or DNA damage. A total of 68 publications were identified. Thirty-four studies (50.0%) evaluated the effect of medical procedures or treatments on γH2AX levels; 20 (29.4%) monitored γH2AX in specific pathological conditions with a case/control or case/case design; 5 studies (7.4%) evaluated the effect of environmental genotoxic exposures, and 9 (13.2%) were descriptive studies on cancer and aging. Peripheral blood lymphocytes (44.6%) or biopsies/tissue specimens (24.3%) were the most commonly used samples. γH2AX was scored by optical microscopy as immunostained foci (78%), or by flow cytometry (16%). Critical features affecting the reliability of the assay, including protocols heterogeneity, specimen, cell cycle, kinetics, study design, and statistical analysis, are hereby discussed. Because of its sensitivity, efficiency and mechanistic relevance, the γH2AX assay has great potential as a DNA damage biomarker; however, the technical and epidemiological heterogeneity highlighted in this review infer a necessity for experimental standardization of the assay., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: To identify characteristic computed tomographic (CT) and computer-derived features of hamartomas manifesting as small pulmonary nodules., Methods: Individuals with a diagnosis of hamartoma were identified among participants in the International Early Lung Cancer Action Program and were included if there thin section CT images that included the entire nodule. The CT findings were reviewed to determine the nodule consistency (solid, part-solid, nonsolid), nodule diameter (average of length and width), shape (round, lobulated, neither) and edge (smooth, not smooth). Computer measures of nodule compactness, sphericity, surface regularity and gradient (change in gray-scale between the nodule and the surrounding parenchyma) were determined. Volume doubling time (VDT) was also determined for those with at least two scans with similar imaging acquisitions., Results: A total of 21 cases of hamartomas that had histologic or cytologic confirmation were identified. The median age was 60 and 12 (57%) were men. Average diameter was 10.7 mm (5-20.7 mm). All were solid in consistency and were described by the radiologist as having either round or lobulated shape with a smooth edge. None had pathognomonic radiologic findings for hamartoma. Computer measures demonstrated that all were compact and spherical, with a regular surface and a sharp margin between the nodule and surrounding parenchyma. Of nine on whom the VDT could be calculated, eight had VDTs longer than 450 days., Conclusion: Both radiologist and computer derived features of small hamartomas suggest a consistent presentation for these lesions which may be helpful in distinguishing them from other types of nodules., (Copyright © 2011. Published by Elsevier Inc.)

In our previous study we have identified PACAP, VIP and their receptors in rat malignant peripheral nerve sheath tumor (MPNST) cells, thus showing anti-apoptotic roles. Recently it has been shown that the tumor suppressor neurofibromin, encoded by the Neurofibromatosis type I (NF1) gene, promotes MPNST cells sensitivity to apoptosis after serum withdrawal. In the present study we investigated whether PACAP or VIP negatively regulate NF1 expression under normal or serum-dependent pro-apoptotic culture conditions. Results indicated that serum itself significantly influenced gene and protein levels. In fact, the low NF1 levels of cells cultured in normal serum-containing medium were remarkably increased in cells switched to low- or no-serum after 24h and 48 h. Treatment with 100 nM PACAP or VIP did not affect NF1 expression when using normal amounts of serum, whereas it significantly inhibited transcript and protein levels both in low- or no-serum cultured cells. In particular, PACAP reduced NF1 levels already after 24h in low-serum cultured cells, while VIP showed a similar effect only after serum deprivation. However, both PACAP and VIP downregulated gene and protein levels within 48 h either in low-dose and serum-starved cells. Results were confirmed by fluorescence microscopy, showing that 100 nM PACAP or VIP attenuated neurofibromin cytoplasmic localization only in low- or no-serum cultured cells. The present study provides a comprehensive analysis of both neuropeptides effect on NF1 expression in normal, low- or serum-starved MPNST cells, ameliorating the hypothesis that resistance to apoptosis in serum-deprived cells might be correlated to PACAP-/VIP-induced NF1 inhibition., ((c) 2009 Elsevier Ltd. All rights reserved.)

Background: Fibrillar aggregates of amyloid beta 25-35 (Abeta(25-35)) form rapidly in vitro able to lyse human red blood cells (RBCs). Human sera, albumin, and apolipoprotein E (ApoE) each limit fibrillation and cytotoxicity. Potentially, these substances protect neurons from Abeta(1-40/42) aggregates. Transferrin (TF) is investigated in this study., Methods: The Mattson red blood cells model was employed to determine whether co-incubation of transferrin and Abeta(25-35) prevented lysis. The formation of fibrillar Abeta(25-35) in the presence of transferrin was investigated using Congo red staining and spectrophotometric studies., Results: We found that incubation of 20 muM Abeta(25-35) with physiologic levels of transferrin prevented red blood cells lysis and the formation of macro-aggregates., Conclusions: These in vitro results suggest that transferrin may limit fibrillar beta amyloid formation in vivo and cytotoxicity.

The government of the Marche Region has approved an Act called the "Regional Health Plan" establishing rules for the organization and development of healthcare. The main aim of the general plan is to rationalize the activities of medical laboratories first by making up an inventory of existing facilities and tests performed, and by classifying laboratories on the basis of their specialization and the complexity of tests that they perform.Moreover, the possible role of point-of-care testing and the need for clinical advice by laboratory professionals has also been debated.

Aims: Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way., Methods: Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days., Results: Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months., Conclusions: After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.

Thirty-three patients with ovarian carcinoma who had no evidence of metastases or ascites demonstrated on computed tomography (CT) with and without contrast agent were examined with CT after injection of approximately 3000 cc of a 2.4% solution of nonionic contrast media into the peritoneum. After intraperitoneal injection with CT (IPC CT), 22 were diagnosed as having intraperitoneal metastases. Of these, 19 were found to be true positives and 3 false negatives. Three other patients diagnosed as normal were found to have metastases. In all patients the peritoneum was well outlined and generally any metastases smaller than 1 cm were demonstrated. It was possible to identify compartmentalization of the peritoneum and to determine the location of the lesion to be in the peritoneum or the extraperitoneal space. This information is necessary in the planning of chemotherapy, particularly endoperitoneal chemotherapy. Tiny metastases to the omentum or adherent loops of small bowel could not be seen well.

The present study was aimed to decide whether Na+ influx can be involved in regulation of murine L 1210 leukemia cell growth. Cells were cultivated in the presence of different concentrations of amiloride and cellular growth was monitored by 3H-thymidine incorporation/10(5) cells. This drug inhibited cell growth in concentrations ranging from 1 X 10(-5) to 1 X 10(-3) mmol/ml. Even short time treatments with amiloride caused irreversible alterations: the cells, although survived, lost their ability to divide. The results support the hypothesis that Na+ influx is necessary for the duplication of tumor cells.

The beta-adrenergic compound isoproterenol was used as oxidizable reagent in a whole-cell assay for the detection of bacterial peroxidase activities. Isoproterenol has been shown to constitute a useful reagent for detecting peroxidase activities in enzymatic tests, utilizing standard purified enzymes, and in the microbiological application proposed. The procedure developed is simple and rapid to perform. In contrast to currently used whole-cell tests for bacterial peroxidases, the assay described here does not need preliminary permeabilization; moreover, the compound utilized does not have related toxicological problems. Therefore, the isoproterenol assay may represent a low-cost safe additional peroxidase test in clinical bacteriology.