Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

Altered corticostriatal functional connectivity in individuals with high social anhedonia.

BACKGROUND: Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia. METHOD: Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect. RESULTS: Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression. CONCLUSIONS: Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.

Trial of LVDP regimen (L-asparaginase, etoposide, dexamethasone, and cisplatin, followed by radiotherapy) as first-line treatment for newly diagnosed, stage III/IV extranodal natural killer/T cell lymphoma.

Stage III/IV extranodal natural killer/T cell lymphoma (ENKL) has a poor response and poor survival. Given the sensitivity of ENKL to radiotherapy and the fact that there is no consensus on standard chemotherapy, we conducted a clinical trial of LVDP regimen, combining LVDP chemotherapy (containing etoposide, dexamethasone, L-asparaginase, and cisplatin), followed by radiotherapy as a consolidation therapy regimen, for newly diagnosed patients with stage III/IV ENKL to evaluate the efficacy and safety of this regimen. The primary endpoints were overall response rate (ORR) and survival [overall survival (OS) and progression-free survival (PFS)] at 1 or 2 years, while the secondary endpoints were toxicity and adverse effects. In total, 18 patients were enrolled in this trial from July 2010 to September 2013. The mean completed cycles of chemotherapy was 4.04 (range 1-8 cycles), and the ORR was 50 %. During a mean follow-up of 21.8 months (range 2-51 months), the 1-year OS and PFS rates were 72.2 and 50.0 %, respectively, the 2-year OS and PFS rates were 33.3 and 22.2 %, respectively, and the median OS and PFS were 23.0 and 10.5 months, respectively. Severe adverse effects during therapy included six cases of grade 3/4 bone marrow suppression and one case of grade 3 transaminase increase. Sex, eastern cancer oncology group, performance status, Korean Prognostic Index, International Prognostic index, and bone marrow infiltration may influence the prognosis of advanced-stage ENKL.

Expression of alpha-smooth muscle actin by and contraction of cells derived from synovium.

Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells--including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells.

Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand.

PURPOSE: Cantharidin, a natural toxin, is the active substance of mylabris and has antitumor effects in man. Norcantharidin, the demethylated analogue of cantharidin, has been used in the treatment of patients with primary hepatoma and those with leukopenia in China. The present study was designed to investigate whether norcantharidin exerts cytotoxic activity against colorectal cancer cells by inducing apoptosis and to examine the possible mechanism in the phenomenon. METHODS: Inhibition of proliferation of norcantharidin on Colo205, HT-29, and SW480 colorectal cancer cells was determined by the trypan blue dye exclusion test. Apoptosis of norcantharidin-treated cells was determined by morphological analysis, agarose gel DNA electrophoresis, and quantitated by flow cytometry after staining with propidium iodide. Cell cycle and the cell surface expression of the CD95/CD95 ligand were evaluated by flow cytometry. Caspase 8-like protease and protein phosphatase 1 and 2A activities were also analyzed. RESULTS: Treatment with norcantharidin of colorectal cancer cells not only inhibited cell proliferation, but also induced apoptosis. Norcantharidin induced apoptosis mainly in two phases: rapid apoptosis in S-phase cells and delayed apoptosis in G2/M arrested cells. Treatment with norcantharidin resulted in an upregulation of the CD95 receptor and CD95 ligand on the cell surface. Furthermore, stimulation with anti-CD95 monoclonal antibody (mAb) resulted in further induction of apoptosis after treatment with norcantharidin. In addition, the apoptosis-inducing effect of norcantharidin was almost completely inhibited by anti-CD95 ligand mAb. Norcantharidin-treated cells showed the activation of caspase 8. Both zVAD-FMK (a broad range caspase inhibitor) and IETD-FMK (a caspase-8 inhibitor) showed apparent inhibition of the apoptosis-inducing effect. Norcantharidin did not show an inhibitory effect on protein phosphatase. CONCLUSIONS: These results suggest that norcantharidin triggers apoptosis in colorectal cancer cell lines via the activation of the CD95 receptor/ligand system, and that this agent may be useful for developing new therapeutic regimens for the treatment of colorectal carcinoma.