Employment Consequences of COVID-19 for People with Disabilities and Employers

Journal of Occupational Rehabilitation - Purpose The COVID-19 pandemic has disproportionately affected the lives of people with disabilities (PWD). How the pandemic affects the employment of PWD...     

Chromosomal instability and marker chromosome evolution in oral squamous cell carcinoma

Squamous cell carcinoma of the head and neck and its subset, oral squamous cell carcinoma (OSCC), arise through a multistep process of genetic alterations as a result of exposure to environmental agents, such as tobacco smoke, alcoholic beverages, and viruses, including human papillomavirus. We and others have shown that the karyotypes of OSCC are near-triploid and contain multiple structural and numerical abnormalities. However, despite a background of clonal chromosomal aberrations, individual cells within a culture express many nonclonal numerical and structural abnormalities, termed chromosomal instability (CIN). To evaluate CIN in oral cancer cells, we isolated clones from two OSCC cell lines and carried out classical cytogenetic analysis, fluorescence in situ hybridization using centromere-specific probes, and spectral karyotyping. We observed variation in chromosome number within clones and between clones of the same cell line. Although similar numbers of centromeric signals for a particular chromosome were present, "homologs" of a chromosome varied structurally from cell to cell (marker chromosome evolution) as documented by classical and spectral karyotyping. In addition to the numerical chromosome variations within a clone, we observed marker chromosome evolution by structural chromosome alterations. It appears that both intrinsic structural alterations and extrinsic cytoskeletal factors influence chromosome segregation, resulting in individual tumor cells that express unique karyotypes. We show that CIN and marker chromosome evolution are essential acquired features of neoplastic cells. Proliferation of this heterogeneous cell population may provide some cells with the ability to evade standard therapies.     

SNOMED takes the next step

Healthcare terminologies SNOMED and the Read Codes have been around for a long time. Now, a new terminology combining the two promises to take the industry one step closer to realizing the vision of an electronic patient record. Here 's a sneak peek at SNOMED CT.     

The level of DNA modification by (+)-syn-(11S,12R,13S,14R)- and (-)-anti-(11R,12S,13S,14R)-dihydrodiol epoxides of dibenzo[a,l]pyrene determined the effect on the proteins p53 and p21WAF1 in the human mammary carcinoma cell line MCF-7.

The polycyclic aromatic hydrocarbon (PAH) dibenzo[a,l]pyrene (DB[a,l]P), the most carcinogenic PAH tested in rodent bioassays, exerts its pathobiological activity via metabolic formation of electrophilically reactive DNA-binding fjord region (+)-syn-(11S,12R,13S,14R)- or (-)-anti-(11R,12S,13S,14R)-DB[a,l]P-dihydrodiol epoxides (DB[a,l]-PDEs). DB[a,l]P is metabolized to these DB[a,l]PDEs which bind to DNA in human mammary carcinoma MCF-7 cells. The molecular response of MCF-7 cells to DNA damage caused by DB[a,l]PDEs was investigated by analyzing effects on the expression of the tumor suppressor protein p53 and one of its target gene products, the cyclin-dependent kinase inhibitor p21WAF1. Treatment of MCF-7 cells with (+)-syn- and (-)-anti-DB[a,l]PDE at a concentration range of 0.001-0.1 microM resulted in DB[a,l]PDE-DNA adduct levels between 2 and 30, and 3 and 80 pmol/mg DNA, respectively, 8 h after exposure. (-)-anti-DB[a,l]PDE exhibited a higher binding efficiency that correlated with a significantly stronger p53 response at low concentrations of the dihydrodiol epoxides. The level of p53 increased by 6-8 h after treatment. The p21WAF1 protein amount exceeded control levels by 12 h and remained elevated for 96 h. At a dose of 0.01 microM (+)-syn-DB[a,l]PDE, an increase in p21WAF1 was observed in the absence of a detectable change in p53 levels. The results indicate that the increase in p53 induced by DB[a,l]PDEs in MCF-7 cells requires an adduct level of approximately 15 pmot/mg DNA and suggest that the level of adducts rather than the specific structure of the DB[a,l]PDE-DNA adduct formed triggers the p53 response. The PAH-DNA adduct level formed may determine whether p53 and p21VAF1 pathways respond, resulting in cell-cycle arrest, or fail to respond and increase the risk of mutation induction by these DNA lesions.     

Spherical tissue sampling in 3-dimensional power Doppler angiography: a new approach for evaluation of ovarian tumors.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of virtual spherical tissue sampling using 3-dimensional (3D) ultrasound power Doppler angiography to enhance differentiation between normal and pathologic ovaries. METHODS: Twenty-seven cases with ovarian tumors were analyzed: 14 with invasive cancers and 13 with borderline tumors confirmed by surgery. The control subjects consisted of 53 healthy ovulating women. Ultrasound scans were done, and 3D volumes were analyzed with 3-/4-dimensional software for personal computers based on 3D vascularity indices: the vascularization index, flow index, and vascularization-flow index. A virtual spherical tissue sample of 1 cm3 was taken from the place of the highest vessel density contained completely within the contours of the ovary. Calculations for the whole solid volume were done for comparison. RESULTS: Vascularity indices for both 1-cm3 spherical samples and whole dense parts of the ovaries were compared in the following groups: (1) ovarian tumors versus controls, (2) normal ovaries in the proliferative versus secretory phase, (3) invasive cancers versus borderline tumors, (4) invasive cancers versus normal ovaries, and (5) borderline tumors versus normal ovaries. Spherical 1-cm3 sampling achieved a higher degree of discrimination between the groups compared with the whole solid-part approach. CONCLUSIONS: Spherical 1-cm3 sampling of ovarian tissue with 3D ultrasound power Doppler angiography is a sensitive and promising approach to differentiate between ovarian tumors and normal ovaries. It opens the possibility to implement objective computerized positioning, standardized comparison, and analysis of ovarian tumors.     

Increased production of proinflammatory cytokines in adipose tissue of patients with end-stage renal disease

ObjectiveThe number of patients with end-stage renal disease (ESRD) is rising and these patients are at higher risk of cardiovascular disease. We studied the role of hormonal production of adipose tissue in the development of chronic inflammation in patients with ESRD before kidney transplantation.MethodsFifteen women with ESRD and 17 healthy women (control) underwent single blood drawing and visceral and subcutaneous adipose tissue sampling during surgery (kidney transplantation in the ESRD group or cholecystectomy in the control group). Serum concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-α, leptin, adiponectin, resistin, monocyte chemoattractant protein-1 were measured. Messenger RNA expression of the same hormones, adiponectin receptors 1 and 2 and immunocompetent cell marker CD68 in subcutaneous and visceral samples were measured using real-time polymerase chain reaction. Adipose tissue was examined immunohistochemically for CD68-positive cells.ResultsSerum concentrations of C-reactive protein, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 were significantly higher in the ESRD versus control group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-α and CD68 were significantly increased in the ESRD versus control group. Adiponectin receptor-1 and monocyte chemoattractant protein-1 mRNA expressions were significantly higher in visceral but not in subcutaneous adipose tissue of the ESRD group. Messenger RNA expressions of resistin, leptin, adiponectin, interleukin-6, and adiponectin receptor-2 in both fat depots did not significantly differ between groups. Increased infiltration of subcutaneous and visceral adipose tissue with CD68-positive immunocompetent cells was found in the ESRD group by histologic examination.ConclusionSubcutaneous and visceral adipose tissues in ESRD express higher amounts of proinflammatory cytokines and may play a role in the development of systemic inflammation.