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Background: Advances in the treatment of brain tumours have increased the number of long-term survivors, but at the cost of side effects following cranial radiotherapy ranging from neurocognitive deficits to outright tissue necrosis. At present, there are no tools reflecting the molecular mechanisms underlying such side effects, and thus no means to evaluate interventional effects after cranial radiotherapy. Therefore, fluid biomarkers are of great clinical interest.Objective: Cerebrospinal fluid (CSF) levels of proteins involved in inflammatory signalling, synaptic plasticity and extracellular matrix (ECM) integrity were investigated following radiotherapy to the brain.Methods: Patients with small-cell lung cancer (SCLC) eligible for prophylactic cranial irradiation (PCI) were asked to participate in the study. PCI was prescribed either as 2 Gy/fraction to a total dose of 30 Gy (limited disease) or 4 Gy/fraction to 20 Gy (extensive disease). CSF was collected by lumbar puncture at baseline, 3 months and 1 year following PCI. Protein concentrations were measured using immunobased assays or mass spectrometry.Results: The inflammatory markers IL-15, IL-16 and MCP-1/CCL2 were elevated in CSF 3 months following PCI compared to baseline. The plasticity marker GAP-43 was elevated 3 months following PCI, and the same trend was seen for SNAP-25, but not for SYT1. The investigated ECM proteins, brevican and neurocan, showed a decline following PCI. There was a strong correlation between the progressive decline of soluble APPα and brevican levels.Conclusion: To our knowledge, this is the first time ECM-related proteins have been shown to be affected by cranial radiotherapy in patients with cancer. These findings may help us to get a better understanding of the mechanisms behind side effects following radiotherapy. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyse the psychosocial and physical effects of a reorganisation of data entry work at a data processing unit with 153 employees. The reorganisation was planned to redistribute the repetitive work and improve health and satisfaction as well as efficiency. Methods used were questionnaires and, for a sub-group of 22 participants, interviews, diaries and video recordings. During the one-and-a-half-year study period the data processing unit was closed down and the employees transferred to units with more varied tasks. The reorganisation gave opportunities to improve working conditions. The results of this study show that important improvements were achieved. The majority of the 22 participants got less data entry work and the changes permitted a better work-load distribution. However, the work content after the reorganisation still did not provide satisfactory mental variation for most of the subjects, and the changes did not seem to affect health complaints. [ABSTRACT FROM AUTHOR]

Objective: Treatment of pediatric brain tumors is associated with potential long-term cognitive sequelae. Patients treated with craniospinal irradiation for posterior fossa tumors are at high risk. New biomarkers that could help to differentiate treatment effects from other causes of cognitive dysfunction would be valuable in tailoring optimal survivorship care. Biomarkers that reflect biological mechanisms behind treatment-associated cognitive decline would also be important in the evaluation of future treatment regimens for pediatric brain or skull base tumors., Methods: In this biomarker-finding study, 10 adult survivors of pediatric medulloblastoma, skull base tumors, and posterior fossa low-grade glioma underwent study specific lumbar puncture at a minimum of 17 years following treatment. We analyzed cerebrospinal fluid biomarkers reflecting neuron and astrocyte integrity, amyloid metabolism, inflammation, extracellular matrix, synaptic integrity, and blood-brain barrier function. The values were compared with biomarker levels in healthy controls of comparable age., Results: Biomarkers reflecting neuronal injury (neurofilament light chain protein), astrocyte injury or activation (glial fibrillary acidic protein) as well as inflammation (YKL-40) were significantly elevated in cancer survivors compared to controls. Biomarkers reflecting amyloid metabolism showed a pattern of decrease in patients treated for medulloblastoma., Interpretation: The results suggest a potential chronic low-grade neurodegeneration and astrocyte activation in patients treated for pediatric brain or skull base tumors. Protein biomarkers of CNS disease could potentially be used to increase our understanding of the contribution from different tumor treatments with regard to long-term symptoms in cancer patients., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Treatment of malignant childhood posterior fossa tumors (CPFT) often includes surgical resection and craniospinal radiotherapy (CSI). Nasopharyngeal tumors in childhood (CNPHT) are often treated with surgery and radiotherapy (RT), leading to incidental brain irradiation. RT to the developing brain is associated with risks for cognitive impairments. We studied cognitive functioning, health-related quality of life (HRQOL), fatigue, and psychological distress, in adult survivors of CPFT and CNPHT, representing two groups, which had received high and low radiation dose-exposure to the brain, respectively. Cognitive tests were used to compare CPFT (n = 12) and CNPHT (n = 7) survivors to matched healthy controls (n = 28). HRQOL data was compared to the general population (GP) (n = 1415-1459). Average follow-up was 23 (CPFT) and 19 years (CNPHT). CPFT survivors had significant deficits in all cognitive domains. CNPHT survivors showed results below the control group but differed statistically only on one executive test. HRQOL-ratings indicated that both groups had similar self-reported cognitive problems. CPFT survivors reported more emotional problems and fatigue. Anxiety was seen in both CPFT and CNPHT survivors. This study confirmed long-term cognitive sequelae after RT in adult survivors of CPFT,and possible RT-induced cognitive deficits in adult CNPHT survivors.

Objectives: Curative treatment of nasal cavity and paranasal sinus cancer is challenging due to the proximity to critical anatomical structures. The purpose of this study was to analyze the impact of trimodality therapy with preoperative chemotherapy and reduced-dose radiotherapy followed by organ-preserving surgery for treating patients with nasal cavity and paranasal sinus cancer., Methods: This retrospective study included all 156 patients diagnosed with sinonasal cancer in western Sweden between 1986 and 2009. We determined the treatment selection pattern and treatment outcomes for 79 patients treated with preoperative chemoradiotherapy., Results: Squamous cell carcinoma was the most common histology. The five-year overall survival was 54%, and 85% of these patients had T3 or T4 tumors. The five-year cumulative incidence rate of local recurrence was 32%. The five-year overall survival in patients with squamous cell carcinoma and adenocarcinoma was 45% and 76%, respectively. The median preoperative radiation dose was 48 Gy. Orbital exenteration was performed in 7% of patients., Conclusions: Preoperative chemoradiotherapy may be beneficial for patients with advanced sinonasal cancer when primary radical surgery is challenging. Survival outcomes were comparable to outcomes reported in the literature despite conservative surgery and relatively low radiation doses in patients with locally advanced tumors.

Immunofluorescence quantification of γH2AX foci is a powerful approach to quantify DNA double-strand breaks induced by cancer therapy or accidental exposure to ionizing radiation. Here we report a modification to the γH2AX immunofluorescence labeling method, whereby cells are stained in-solution before being spotted and fixed onto microscope slides. Our modified method allows arraying of 16 patient samples/slide ready for foci counting in 2 h and demonstrated reliably detection of γH2AX foci in mononuclear cells prepared from patients who had undergone radiation therapy.

The aim of the study was to evaluate four different modes of human-computer interaction. The modes were: use of the keyboard alone as input device, use of keyboard and mouse, use of keyboard and mouse with a three-dimensional arm support, and use of a keyboard with a Trackpoint device in its centre. Ten women and 10 men volunteered to participate. Questions asked were whether working in the different modes influenced shoulder and forearm muscular load differently during word processing, and how much strain on the neck, shoulder and arms subjects perceived in the different modes. Muscular load was studied with electromyography in three shoulder muscles and three forearm muscles. The subjects also rated the different modes in one questionnaire concerning perceived strain and in one concerning preference for any of the modes tested. Intra-individual analysis for each muscle and mode showed two possible ways of decreasing the strain from computer mouse work on the shoulder muscles--either to use Trackpoint or to use the mouse combined with the movable arm support. However, both of these computer-interaction modes increased the muscular load in the hand and forearm.

The present aim was to measure and quantify upper-arm elevation and to find how changed work organization and work tasks influence arm movement during a working day. Sixteen female office workers participated in the study. Their main work was statistical data entry. Upper-arm elevation was measured on two occasions separated by 18 months, i.e., before and after a change of work organization. The measurements were performed during the whole of one ordinary working day. The differences between the two measurements were mostly non-significant. Arm elevation remained essentially below 30 degrees during the main time of the working day, and the subjects worked with limited arm movements. Despite new alternative office tasks, they did not achieve a change in their habitual arm postures, or in their neck-and-shoulder disorders.

This study investigated how ergonomic design influences neck-and-shoulder muscle strain, through keyboard assessment. Muscular activity was measured electromyographically (EMG) from six muscles in the forearm and shoulders of eight experienced typists using each of five different types of keyboard: one mechanical, one electromechanical, and one electronic typewriter; one personal computer/word processor (PC-XT) keyboard; and one angled at 20 degrees in the horizontal plane. The impact on muscular activity of using a palmrest was also studied. The mechanical typewriter induced a higher strain in the forearm and finger muscles than did the modern typewriters and keyboards. These induced no different strain on the neck-and-shoulder muscles, except for the right shoulder muscle, which was more active with the electronic typewriter than with the other machines. Using a palmrest did not decrease the strain on the muscles investigated. Use of the 'angled' PC-XT keyboard did not influence the measured muscular load on the forearm and finger muscles compared to typing on an ordinary PC-XT keyboard, but decreased the extensor muscular strain compared to the electronic typewriter.