Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Relationship of knee joint proprioception to pain and disability in individuals with knee osteoarthritis.

Proprioception plays an integral role in neuromotor control of the knee joint and deficits in knee joint proprioception are well documented in individuals with knee osteoarthritis (OA). However, the functional relevance of these deficits is not clear. This cross-sectional study evaluated the relationship between knee joint proprioception and pain and disability in a large cohort of individuals with knee OA. Two hundred and twenty participants (145 F, 75 M) with symptomatic knee OA were recruited from the community. Five non-weight bearing active tests with ipsilateral limb matching responses were performed at 20 degrees and 40 degrees flexion to measure knee joint position sense. Pain and disability were assessed by self-reported questionnaires and objective measures of balance and gait. Results showed little association between knee joint position sense variables and measures of pain and disability (r values <0.24, most p>0.05). When comparing participants with the worst and best joint position sense, no significant differences in pain and disability could be found (p>0.05). While our study design does not allow causality to be established, these results suggest that deficits in joint position sense may be due to factors other than pain and that deficits are not large enough to impact upon disability.     

The efficacy of 2 different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate the efficacy of methylphenidate in treating adults with attention-deficit hyperactivity disorder (ADHD), using subjective (self-report) and objective (computerized test) measures. METHOD: This double-blind crossover trial of placebo vs methylphenidate included subjects with childhood and current ADHD symptoms, IQs above 80, no other psychiatric condition explaining their difficulties or requiring other treatment, and no substance abuse in the previous 6 months. We administered 10 mg 3 times daily of medication (that is, placebo or methylphenidate) for 2 weeks. On the final day, subjects completed self-report measures and were tested on computerized tests. We then increased dosage to 15 mg 3 times daily for 2 weeks and administered a complete reassessment on the final day. Following a 1-week washout, we repeated this process on the second medication (that is, placebo or methylphenidate). RESULTS: Thirty adults with ADHD participated. Self-report measures and computerized tests showed significant improvements in ADHD symptoms on methylphenidate, compared with placebo. Other psychiatric symptoms (notably, anxiety and depression) were alleviated with methylphenidate. There was no significant difference between the 2 dosages of methylphenidate. CONCLUSION: Methylphenidate is effective in improving ADHD symptoms in adults with ADHD, is well tolerated, and has minimal side effects.     

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in a murine model of pulmonary eosinophilia and high IgE level.

T lymphocytes and eosinophils are probably involved in the pathogenesis of allergic bronchopulmonary aspergillosis (ABPA), a disease characterized by pulmonary eosinophilia and high serum and lavage IgE levels. We recently developed a murine model of ABPA. To investigate the mechanisms of T lymphocyte and eosinophil recruitment to the lung in this disease, we examined the expression of ICAM-1 in the lung tissue of mouse challenged with Aspergillus fumigatus (Af) antigen. C57B1/6 mice were intranasally exposed to Af (Af group) or saline (control group) three times a week for 1, 2 or 3 weeks. On days 4, 7, 14 and 21, mice were killed and lung tissue was fixed in acetone and embedded in glycol methacrylate. Serial 2-microns sections were stained with chromotrope 2R and MoAbs against ICAM-1, CD11a/CD18 (LFA-1) and CD3. Af-challenged mice presented significant increases in eosinophil, T lymphocyte and LFA-1-positive cell count and up-regulated expression of ICAM-1 in the lung tissue at all the time points examined. ICAM-1 expression intensity correlated with the number of T lymphocytes (r = 0.59, P < 0.01), LFA-1-positive cells (r = 0.68, P < 0.001), but not of eosinophils (r = -0.24, P > 0.05). These findings suggest that up-regulation of ICAM-1 expression is involved in the inflammatory process of this murine model of ABPA, and that this up-regulation may be more relevant to the the T lymphocyte accumulation in the lung.     

Development of a Programme Theory for Early Intervention Vocational Rehabilitation: A Realist Literature Review

Journal of Occupational Rehabilitation - Purpose Little is currently known about how early intervention vocational rehabilitation (EIVR) works for people with newly acquired neurological conditions...     

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.