The Kawa model: The power of culturally responsive occupational therapy

The Kawa (Japanese for river) model, developed by Japanese and Canadian rehabilitation professionals, presents an important and novel alternative to contemporary ‘Western’ models of rehabilitation. Rather than focussing primarily on the individual client, the Kawa model focusses on ‘contexts’ that shape and influence the realities and challenges of peoples' day-to-day lives. The first substantial model of rehabilitation practice developed outside of the West illuminates the transactional quality of human-environment dynamics and the importance of inter-relations of self and others through the metaphor of a river's flow. The model's reflection of Eastern thought and views of nature presents a useful point of comparison to familiar rational and mechanical explanations of occupation and well-being. In this article, the rationale for an alternative model in rehabilitation is presented, followed by an explanation of the structure and concepts of the Kawa model. Implications for culturally responsive practice as well as the model's significance to the advancement of culturally safe rehabilitation worldwide are discussed.     

Immunostimulatory oncolytic activity of coxsackievirus A11 in human malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive solid cancer with a poor prognosis, whereas coxsackievirus A11 (CVA11) is a potential oncolytic virus for cancer treatment. We here investigated the oncolytic activity of CVA11 with human MPM cell lines. CVA11 infection was cytotoxic in all six MPM cell lines examined and showed no or minimal cytotoxicity toward normal human normal cell lines. MPM cells with a higher surface level of intercellular adhesion molecule-1 (ICAM-1) expression tended to be more susceptible to CVA11-induced cytotoxicity, and a neutralizing antibody to ICAM-1 attenuated such cytotoxicity. CVA11 infection activated signaling by Akt and extracellular signal-regulated kinase (ERK) pathways, and inhibitors of such signaling also abrogated CVA11-mediated cytotoxicity. Furthermore, CVA11 infection-triggered multiple modes of tumor cell death including apoptosis, pyroptosis, and necroptosis, and such death was accompanied by the release or exposure of the proinflammatory cytokine interleukin-1β and damage-associated molecular patterns such as calreticulin, high-mobility group box-1, annexin A1, and heat shock protein 70, which are hallmarks of immunogenic cell death. Notably, in vivo treatment of human MPM xenografts with intratumoral CVA11 injection resulted in significant suppression of tumor growth in SCID mice, and all mice infected with CVA11 showed no significant change in body weight. Our findings collectively suggest that the oncolytic activity of CVA11 for MPM is dependent on ICAM-1 as a virus receptor, as well as on Akt and ERK signaling, and that oncolytic virotherapy with CVA11 is a promising treatment modality with immunostimulatory activity for human MPM.     

Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes.

Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age-matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.     

Aldehyde dehydrogenase 1 is associated with recurrence‐free survival but not stem cell‐like properties in hepatocellular carcinoma

Aim: It has been reported that aldehyde dehydrogenase 1 A1 (ALDH1) could be not only a normal stem cell marker but also a cancer stem cell marker. ALDH1 expression could be a predictor of poor prognosis in a wide range of cancers. However, the role of ALDH1 in hepatocellular carcinoma (HCC) remains unclear. Method: We conducted loss‐of‐function assays for ALDH1 by using short‐hairpin RNA in HCC cells and evaluated the correlation between ALDH1 expression and clinicopathological features based on immunohistochemical assessment of 49 primary HCC tissues. Results: Neither cell proliferation nor the anchorage‐independent sphere formation ability of HCC cells were altered after ALDH1 knockdown. Flow cytometric analyses revealed that ALDH1 knockdown showed no remarkable change in the proportion of epithelial cell adhesion molecule (EpCAM)⁺ tumor‐initiating cells. Although non‐tumor tissues in primary HCC samples diffusely and homogenously expressed ALDH1 at low levels, tumor tissues contained cells with high levels of ALDH1 expression at varying frequencies. Primary HCC samples were categorized as ALDH1‐high or ALDH1‐low based on the percentage of ALDH1‐overexpressing cells. ALDH1‐high HCC was characterized by low serum levels of α‐fetoprotein (P < 0.01) and well‐differentiated pathology (P = 0.03). Multivariate analysis showed that high ALDH1 expression was a favorable prognostic factor in recurrence‐free survival of HCC (P = 0.02). Conclusion: Our findings show that ALDH1 expression has little association with stem cell‐like features in HCC cells. ALDH1 might function as a differentiation marker rather than a stem cell marker in HCC.     

Comparison between in vitro properties of washed platelet concentrates suspended in M-sol and those in BRS-A,both of which were prepared with an automated cell processor

Background

Washed platelet concentrate (WPC) is prepared manually in general, but automated preparation is desirable to minimize variation in the WPC quality and enhance WPC production. Recently, the software was improved for an automated cell processor (ACP) to control all processes of WPC preparation. M-sol and BRS-A, which are mixtures of medical solutions, are widely used for WPC preparation with a manual method in Japan. In this study, we prepared WPC suspended in M-sol (WPC-M) or BRS-A (WPC-B) with the ACP, and compared their in vitro properties during 7-day storage.

Reactivation of hepatitis B virus after rituximab‐containing treatment in patients with CD20‐positive B‐cell lymphoma

BACKGROUND:

Reactivation of hepatitis B virus (HBV) after rituximab‐containing chemotherapy in patients with B‐cell lymphoma has been recognized as a potentially serious complication in HBV immune patients.

METHODS:

To determine the HBV reactivation in patients treated with rituximab, a retrospective study of HBV‐related markers was performed before and after rituximab‐containing treatment in 261 consecutive patients with CD20‐positive B‐cell lymphoma.

RESULTS:

Of the 261 patients, 230 patients were tested for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti‐HBc) before treatment. Fifty‐six (24.3%) of 230 patients were anti‐HBc positive, and the remaining 174 (75.6%) patients were anti‐HBc negative. Among the 56 anti‐HBc–positive patients, 5 (8.9%) became HBsAg positive (HBV reactivation), whereas none of the 174 anti‐HBc–negative patients became HBsAg positive with a median follow‐up of 24 months (P = .001). Among the 5 patients with HBV reactivation, 4 were negative for antibody to HBsAg (anti‐HBs), and 1 patient was positive for anti‐HBs. All 5 of these patients were treated successfully with entecavir on detection of HBsAg, although 4 of the 5 patients exhibited mild to moderate elevation of alanine aminotransferase. Among 56 anti‐HBc–positive patients, those negative for anti‐HBs had a higher probability of developing HBV reactivation compared with those positive for anti‐HBs (4 of 19; 21.1% vs 1 of 37; 2.7%, P = .014).

CONCLUSIONS:

Patients with isolated anti‐HBc are at high risk of HBV reactivation and should be monitored closely for HBsAg, anti‐HBs, HBV‐DNA, and transaminase levels during and after rituximab‐containing treatment. Although preemptive use of entecavir enabled successful management of HBV reactivation, mild to moderate hepatic flare was still observed. These approaches should be further evaluated in a prospective study with regard to clinical usefulness, safety, and cost‐effectiveness. Cancer 2010. © 2010 American Cancer Society.     

MRI demonstration of uncal herniation caused by arachnoid cyst in the Sylvian fissure

Summary We report a case of arachnoid cyst in the Sylvian fissure which progressed to uncal herniation. MRI was shown to be superior in visualizing uncal herniation.     

Ultrastructural effects of granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) on rat neutrophils and monocytes

Human granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) were administered intravenously to rats, and their effects on neutrophils and monocytes were examined by electron microscopy. G-CSF increased the number of cytoplasmic granules in neutrophils. It also enhanced maturation of the nuclear shape in the neutrophils, while chromatin condensation and peroxidase distribution remained immature. M-CSF induced proliferation of monocytes in peripheral blood and bone marrow, but did not affect morphology or distribution of peroxidase reactivity. This study was presented at the 25th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Matsumoto, September 28–30, 1993.