Disability digital divide: survey of accessibility of eHealth services as perceived by people with and without impairment.

BACKGROUND: Sustainable and effective eHealth requires accessibility for everyone. Little is known about how accessibility of eHealth is perceived among people with various impairments. The aim of this study was to compare use and perceived difficulty in the use of eHealth among people with and without impairment, and how different types of impairment were associated with perceived difficulty in the use of eHealth. METHODS: This study used data collected in a nationwide survey in Sweden. Snowball sampling was used to recruit participants with self-reported impairment, from June to October 2019. In February 2020, the survey was posted to people in the general population who were matched to the participants with impairment by age, gender and county of residence. Multiple logistic regression was used to analyse the use of four eHealth services, and perceived difficulty in the use of six eHealth services. RESULTS: In total, 1631 participants with, and 1084 participants without impairment responded to the survey. Participants with impairment reported less use and more difficulty in the use of all eHealth services as compared to participants without impairment. When comparing types of impairment, booking healthcare appointments online was least used and most avoided by participants with communication, language and calculation impairments (adjusted odds ratio (aOR) use 0.64, 95% confidence interval (95%CI) 0.49-0.83; aOR avoid 1.64, 95%CI 1.19-2.27), and intellectual impairments (aOR use 0.28, 95%CI 0.20-0.39; aOR avoid 2.88, 95%CI 1.86-4.45). The Swedish national web-portal for health information and services, 1177.se, was reported difficult to use the most among participants with communication, language and calculation impairments (aOR 2.24, 95%CI 1.50-3.36), deaf-blindness (aOR 11.24, 95%CI 3.49-36.23) and hearing impairment (aOR 2.50, 95%CI 1.17-5.35). CONCLUSIONS: The results confirm the existence of an eHealth disability digital divide. People with impairment were not one homogeneous group, but differed in perceived difficulties in regard to eHealth. Based on a purposeful subgrouping of impairments, we showed that people with communication, language and calculation impairments, and intellectual impairments, reported least use and most difficulty in using eHealth. The findings can guide further research in creating eHealth that is accessible for all, including those with the most significant difficulties.

Outcome prediction for patients assessed by the medical emergency team: a retrospective cohort study.

BACKGROUND: Medical emergency teams (METs) have been implemented to reduce hospital mortality by the early recognition and treatment of potentially life-threatening conditions. The objective of this study was to establish a clinically useful association between clinical variables and mortality risk, among patients assessed by the MET, and further to design an easy-to-use risk score for the prediction of death within 30 days. METHODS: Observational retrospective register study in a tertiary university hospital in Sweden, comprising 2,601 patients, assessed by the MET from 2010 to 2015. Patient registry data at the time of MET assessment was analysed from an epidemiological perspective, using univariable and multivariable analyses with death within 30 days as the outcome variable. Predictors of outcome were defined from age, gender, type of ward for admittance, previous medical history, acute medical condition, vital parameters and laboratory biomarkers. Identified factors independently associated with mortality were then used to develop a prognostic risk score for mortality. RESULTS: The overall 30-day mortality was high (29.0%). We identified thirteen factors independently associated with 30-day mortality concerning; age, type of ward for admittance, vital parameters, laboratory biomarkers, previous medical history and acute medical condition. A MET risk score for mortality based on the impact of these individual thirteen factors in the model yielded a median (range) AUC of 0.780 (0.774-0.785) with good calibration. When corrected for optimism by internal validation, the score yielded a median (range) AUC of 0.768 (0.762-0.773). CONCLUSIONS: Among clinical variables available at the time of MET assessment, thirteen factors were found to be independently associated with 30-day mortality. By applying a simple risk scoring system based on these individual factors, patients at higher risk of dying within 30 days after the MET assessment may be identified and treated earlier in the process.

Pyrrole Hemithioindigo Antimitotics with Near-Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single-Cell Precision*.

We report the first cellular application of the emerging near-quantitative photoswitch pyrrole hemithioindigo, by rationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubs allow simultaneous visible-light imaging and photoswitching in live cells, delivering cell-precise photomodulation of microtubule dynamics, and photocontrol over cell cycle progression and cell death. This is the first acute use of a hemithioindigo photopharmaceutical for high-spatiotemporal-resolution biological control in live cells. It additionally demonstrates the utility of near-quantitative photoswitches, by enabling a dark-active design to overcome residual background activity during cellular photopatterning. This work opens up new horizons for high-precision microtubule research using PHTubs and shows the cellular applicability of pyrrole hemithioindigo as a valuable scaffold for photocontrol of a range of other biological targets.

Mandibular resection in patients with head and neck cancer: acute and long-term complications after reconstruction.

BACKGROUND: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient. AIMS/OBJECTIVES: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions. MATERIAL AND METHODS: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24). RESULTS: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication. CONCLUSIONS: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts. SIGNIFICANCE: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.

In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells from Jawbone Compared with Dental Tissue.

Autologous bone transplantation is the current gold standard for reconstruction of jawbone defects. Bone regeneration using mesenchymal stem cells (MSC) is an interesting alternative to improve the current techniques, which necessitate a second site of surgery resulting in donor site morbidity. In this study, we compared the osteogenic ability of jawbone MSC (JB-MSC) with MSC from tissues with neural crest origin, namely, the dental pulp, apical papilla and periodontal ligament. All four types of MSC were isolated from the same patient (n = 3 donors) to exclude inter-individual variations. The MSC growth and differentiation properties were characterized. The osteogenic differentiation potential in each group of cells was assessed quantitatively to determine if there were any differences between the cell types. All cells expressed the MSC-associated surface markers CD73, CD90, CD105, and CD146 and were negative for CD11b, CD19, CD34, CD45 and HLA-DR. All cell types proliferated at similar rates, exhibited similar clonogenic activity and could differentiate into adipocytes and osteoblasts. An alkaline phosphatase assay, OsteoImage™ assay for mineralization and qRT-PCR measuring the genes runx2, ALP and OCN, indicated that there were no significant differences in the osteogenic differentiation ability between the various MSCs. In conclusion, we show that from a small segment of jawbone it is possible to isolate sufficient quantities of MSC and that these cells can easily be expanded and differentiated into osteoblasts. JB-MSC appear to be good candidates for future bone regeneration applications in the craniofacial region.

Shortened life span, bradycardia, and hypotension in mice with targeted expression of an Igf2 transgene in smooth muscle cells.

IGF2 is known to affect the normal development and pathology of the cardiovascular system. We previously created mutant mice with targeted expression of an Igf2 transgene in the smooth muscle cells and showed that these mice spontaneously develop aortic intimal cushions. In the present work, we provide a general description of the phenotype of two independent lines of heterozygous transgenics. These mice showed organomegaly and a shortened life span. The latter trait was stronger in the line with a relatively more marked organomegaly and more pronounced in males than females in both lines. Postmortem histology revealed gross abnormalities of the cardiac architecture, suggesting that transgenic mice may accumulate lethal cardiovascular defects. Accordingly, apparently normal transgenic mice had mild cardiomegaly, an enlarged left ventricle, bradycardia, and hypotension. These observations are discussed in the light of the proposed therapeutic use of IGF2 in human cardiac diseases.

Monocyte derived interleukin (IL)-23 is an important determinant of synovial IL-17A expression in rheumatoid arthritis.

OBJECTIVE: To demonstrate gene expression of interleukin (IL)-17A, IL-23, and IL-12 and to determine the proximity of IL-17A and IL-23 producing cells in rheumatoid synovial tissue. METHODS: Total RNA was isolated from 25 synovial membranes obtained from 20 patients with rheumatoid arthritis (RA). Quantitative real-time polymerase chain reaction was used to measure IL-17A, IL-12p35, IL-23p19, p40, and GAPDH expression. Immunohistochemistry was utilized to determine cell type and proximity of IL-17A, IL-12, and IL-23 in rheumatoid synovium. RESULTS: IL-17A was present in 13/25 synovia. IL-12p35 was present in all samples while IL-23p19 was present in 23/25. p40 was present in 23/25 samples. Of the 2 p40- samples both were IL-23p19 and IL-12p35 positive. Mean expression of IL-23p19 was significantly higher in the IL-17A+ versus IL-17A- synovia (0.10 +/- 0.02 ng vs 0.05 +/- 0.01 ng; p < 0.05). There was no difference in IL-12p35 expression between IL-17A+ and IL-17A- synovia (0.5 +/- 0.21 ng vs 0.38 +/- 0.24 ng; p = 0.2). All IL-17A+ cells were in the vicinity of IL-23+ cells. IL-12+ cells were both close to and removed from IL-17A+ cells. Only a proportion of CD3+T cells appeared to produce IL-17A. CONCLUSION: IL-17A gene expression occurs in only a subset of rheumatoid synovial membranes. IL-23 gene expression is higher in IL-17A+ versus IL-17A- membranes. In keeping with this, IL-17A+ and IL-23+ cells colocalize in synovial membranes. IL-17 is not an absolute requirement in RA but may be important in amplifying the inflammatory response. Anti-IL23 therapies may have a role in those patients with IL-17A expression.

Insulin-like growth factor II plays a central role in atherosclerosis in a mouse model.

Insulin-like growth factor II is a fetal promoter of cell proliferation that is involved in some forms of cancer and overgrowth syndromes in humans. Here, we provide two sources of genetic evidence for a novel, pivotal role of locally produced insulin-like growth factor II in the development of atherosclerosis. First, we show that homozygosity for a disrupted insulin-like growth factor II allele in mice lacking apolipoprotein E, a widely used animal model of atherosclerosis, results in aortic lesions that are approximately 80% smaller and contain approximately 50% less proliferating cells compared with mice lacking only apolipoprotein E. Second, targeted expression of an insulin-like growth factor II transgene in smooth muscle cells, but not the mere elevation of circulating levels of the peptide, causes per se aortic focal intimal thickenings. The insulin-like growth factor II transgenics presented here are the first viable mutant mice spontaneously developing intimal masses. These observations provide the first direct evidence for an atherogenic activity of insulin-like growth factor II in vivo.