Increase in mast cells and hyaluronic acid correlates to radiation-induced damage and loss of serous acinar cells in salivary glands: the parotid and submandibular glands differ in radiation sensitivity.

The detailed mechanisms which can explain the inherent radiosensitivity of salivary glands remain to be elucidated. Although DNA is the most plausible critical target for the lethal effects of irradiation, interactions with other constituents, such as cell membrane and neuropeptides, have been suggested to cause important physiological changes. Moreover, mast cells seem to be closely linked to radiation-induced pneumonitis. Therefore, in the present study the effects of fractionated irradiation on salivary glands have been assessed with special regard to the appearance of mast cells and its correlation with damage to gland parenchyma. Sprague-Dawley strain rats were unilaterally irradiated to the head and neck with the salivary glands within the radiation field. The irradiation was delivered once daily for 5 days to a total dose of 20, 35 and 45 Gy. The contralateral parotid and submandibular glands served as intra-animal controls and parallel analysis of glands was performed 2, 4, 10 or 180 days following the last radiation treatment. Morphological analysis revealed no obvious changes up to 10 days after the irradiation. At 180 days a radiation dose-dependent loss of gland parenchyma was seen, especially with regard to serious acinar cells in parotid gland and acinar cells and serous CGT (convoluted granular tubule) cells in the submandibular gland. These changes displayed a close correlation with a concomitant dose-dependent enhanced density of mast cells and staining for hyaluronic acid. This cell population seems to conform with the features of the connective tissue mast cell type. The parotid seems to be more sensitive to irradiation than the submandibular gland. Thus, the present results further strengthen the role of and the potential interaction of mast cells with radiation-induced tissue injury and alterations in normal tissue integrity

The importance of clinical and labour market histories in psychiatric disability retirement : analysis of the comprehensive Finnish national-level RETIRE data

Objectives Despite the stable incidence of mental disorders in Finland and Europe, mental health-related occupational disability has been increasing. We unveiled the paths to permanent psychiatric disability, recovery, or death, by analysing sequences of labour market participation. Methods The RETIRE register database includes information regarding all persons (n = 42,170) awarded an ICD-10 psychiatric disability pension between 2010 and 2015 in Finland. We identified clusters of typical paths of pre-retirement labour market history. Controlling for major mental disorders, age, and sex, we evaluated factors associated with returning to work (RTW), or death, over a 5-year follow-up period. Results Only 10.5% of the disabled subjects returned to work within the follow-up. Half of them ended up with a permanent disability pension. Seven distinguishable paths to disability were identified. Subjects in the cluster characterized by steady employment were relatively often females, lost their work ability due to affective disorders, and had the highest rate of returning to work (16.3%). Mortality was highest (9%) among the cluster characterized by long-term unemployment. Distributions of major diagnostic groups, as well as age and sex, differed between clusters. After their adjustment in the analysis of RTW or death, the identified labour market history paths prior to losing work ability remained as important independent prognostic factors for both outcomes. Conclusions The complex retirement process involves identifiable clinical and contextual associating factors. Labour market history patterns associate with varying prognoses after psychiatric retirement. Prolonged unemployment appears as a predictor of relatively poor prognoses, whereas employment indicates the opposite.Peer reviewe

Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis

We report a case of rapid eradication of melanoma brain metastases and simultaneous near-fatal encephalomyelitis following double immune checkpoint blockade. Brain damage marker S-100B and C reactive protein increased before symptoms or signs of encephalomyelitis and peaked when the patient fell into a coma. At that point, additional brain damage markers and peripheral T cell phenotype was analyzed. The analyses were repeated four times during the patient’s recovery. Axonal damage marker neurofilament light polypeptide (NFL) and astrocytic damage marker glial fibrillar acidic protein (GFAP) were very high in blood and cerebrospinal fluid and gradually normalized after immunosuppression and intensive care. The costimulatory receptor inducible T cell costimulatory receptor (ICOS) was expressed on a high proportion of CD4+ and CD8+T cells as encephalomyelitis symptoms peaked and then gradually decreased in parallel with clinical improvement. Both single and double immune checkpoint inhibitor-treated melanoma patients with other serious immune-related adverse events (irAE) (n=9) also expressed ICOS on a significantly higher proportion of CD4+ and CD8+T cells compared with controls without irAE (n=12). In conclusion, our results suggest a potential role for ICOS on CD4+ and CD8+T cells in mediating encephalomyelitis and other serious irAE. In addition, brain damage markers in blood could facilitate early diagnosis of encephalitis