Influence of Perceptual and Conceptual Information on Fear Generalization: A Behavioral and Event-Related Potential Study.

Learned fear can be generalized through both perceptual and conceptual information. This study investigated how perceptual and conceptual similarities influence this generalization process. Twenty-three healthy volunteers completed a fear-generalization test as brain activity was recorded in the form of event-related potentials (ERPs). Participants were exposed to a de novo fear acquisition paradigm with four categories of conditioned stimuli (CS): two conceptual cues (animals and furniture); and two perceptual cues (blue and purple shapes). Animals (C+) and purple shapes (P+) were paired with the unconditioned stimulus (US), whereas furniture (C-) and blue shapes (P-) never were. The generalized stimuli were thus blue animals (C+P+, determined danger), blue furniture (C-P+, perceptual danger), purple animals (C+P-, conceptual danger), and purple furniture (C-P-, determined safe). We found that perceptual cues elicited larger fear responses and shorter reaction times than did conceptual cues during fear acquisition. This suggests that a perceptually related pathway might evoke greater fear than a conceptually based route. During generalization, participants were more afraid of C+ exemplars than of C- exemplars. Furthermore, C+ trials elicited greater N400 amplitudes. Thus, participants appear able to use conceptually based cues to infer the value of the current stimuli. Additionally, compared with C+ exemplars, we found an enhanced late positive potential effect in response to C- exemplars, which seems to reflect a late inhibitory process and might index safety learning. These findings may offer new insights into the pathological mechanism of anxiety disorders.

Correlation between bone marrow dose volumes and acute hematological toxicity in postoperative gynecological cancer patients.

OBJECTIVE: To identify the association between radiation dose volume and acute hematological toxicity (HT) in postoperative gynecological cancer patients receiving whole pelvic radiotherapy (RT) or intensity-modulated RT (IMRT), a principal component regression model was used to calculate HT. METHODS: Women (n=100) receiving with or without chemotherapy RT were retrospectively analyzed, 52 of whom received chemotherapy (paclitaxel and nedaplatin). The pelvis and lumbar vertebrae, defined as the prolong-pelvic bone marrow, were divided into the (1) combined ilium, ischium and pubis and the (2) lumbar vertebrae and the sacrum. The V5-V40 of subsides was calculated. The complete blood counts were recorded weekly. The principal component analysis was performed on volumes which generated the principal components (PCs), followed by using a logistic regression model. RESULTS: Forty-seven patients presented with grade 2-3 HT during RT. Chemotherapy increased the incidence of HT compared with RT alone (70.21% vs. 29.79%; p=0.001). Fifty-three patients with persistent HT developed more serious HT at an earlier stage of RT. The chemotherapy cycles and three PCs associated with grade 2-3 HT was identified to form the resulting principal logistic regression model. CONCLUSION: A new method to calculate the NTCP was achieved by PCs logistic regression.

Hyperthermic intraperitoneal chemotherapy plus high-frequency diathermic therapy followed by intravenous chemotherapy versus intravenous chemotherapy alone for postoperative adjuvant treatment of gastrointestinal cancer: a comparative research study.

PURPOSE: To evaluate the therapeutic efficacy and toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) plus high-frequency diathermic therapy (HFDT) followed by intravenous chemotherapy vs intravenous chemotherapy alone for adjuvant treatment of postoperative gastrointestinal neoplasms. METHODS: Fifty-two gastrointestinal carcinoma patients who were radically operated were enrolled and divided into the treatment group and the control group. In the treatment group, 25 patients were treated with combination of HIPEC+HFDT and subsequent intravenous chemotherapy, while in the control group 27 patients received intravenous chemotherapy alone. Post-therapeutic complications and adverse reactions, time to progression (TTP) and overall survival (OS) were compared between these two groups. RESULTS: Difference in toxic reactions between the two groups was not statistically significant (p>0.05). Postoperative progression- free survival (PFS) rate at 12 and 40 months after radical surgery was 72.0 and 54.0% respectively in the treatment group, and 65.8 and 11.5% respectively in the control group (p=0.108). TTP was statistically significantly longer in the treatment group than in the control group (median TTP 40.1 vs 18.5 months, p=0.027). Postoperative OS at 12 and 20 months after radical surgery was 88.0 and 78.0% respectively in the treatment group and 92.6 and 72.7% in the control group, without significant difference. CONCLUSION: After radical surgery, combination of HIPEC+HFDT and subsequent intravenous chemotherapy brings about superior PFS compared with intravenous adjuvant chemotherapy alone, while having no more complications and adverse reactions.

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty: a randomized clinical trial.

PURPOSE: To compare quality of vision and vision-related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Fifty-four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher-order aberrations (HOAs), contrast sensitivity, straylight and vision-related QOL. RESULTS: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle-corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10-1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision-related QOL (scale 0-100) did not differ significantly between both groups at any time point and improved significantly at 3 months (ß = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (ß = 5 [95% CI: 0 to 9]; p = 0.06). CONCLUSIONS: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision-related QOL improved significantly after surgery, but did not differ between both techniques.

EGFR mutations and HER2/3 protein expression and clinical outcome in Chinese advanced non-small cell lung cancer patients treated with gefitinib.

BACKGROUND: To assess the role of various epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression as predictive markers of responsiveness to gefitinib therapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen received gefitinib 250 mg once daily. All the 106 tumors from these patients were screened for mutations in the EGFR exons 18-24, and 84 tumors were studied by immunohistochemistry for HER2/3 expression and correlated with clinical treatment outcome. RESULTS: Patients with EGFR mutations had a significantly higher overall response rate (ORR), longer time to progression (TTP) and overall survival (OS) compared with those with wild-type receptor. No difference in ORR was observed between patients with exon 19 deletion and patients with other EGFR mutations. ORR in HER2-positive patients was significantly higher than in the HER2-negative group, irrespective of EGFR mutational status, and a trend for better ORR was observed for HER3-positive patients. HER2 and HER3 expression levels were not associated with any difference in terms of TTP and OS. Nevertheless, when considering the subgroups of non-responders to gefitinib, median TTP in patients with mutated EGFR was significantly longer than in those with no mutations (8.0 vs. 3.0 months, P = 0.0065). EGFR-mutated patients had no significant difference in ORR, TTP and OS according to HER2 and/or HER3 expression. CONCLUSIONS: EGFR mutations are effective predictors for gefitinib efficacy in Chinese patients with advanced NSCLC. HER2 and HER3 expression does not provide any additional information for selecting patients most likely to benefit from gefitinib treatment.

Adaptation of humoral memory.

Immunological memory, as provided by antibodies, depends on the continued presence of antibody-secreting cells, such as long-lived plasma cells of the bone marrow. Survival niches for these memory plasma cells are limited in number. In an established immune system, acquisition of new plasma cells, generated in response to recent pathogenic challenges, requires elimination of old memory plasma cells. Here, we review the adaptation of plasma cell memory to new pathogens. This adaptation is dependent upon the influx of plasmablasts, generated in a secondary systemic immune reaction, into the pool of memory plasma cells, the efficiency of competition of new plasmablasts with old plasma cells, and the frequency of infection with novel pathogens. To maintain old plasma cells at frequencies high enough to provide protection and to accommodate as many specificities as possible, an optimal influx rate per infection exists. This optimal rate is approximately three times higher than the minimal number of plasma cells providing protection. Influx rates of plasmablasts generated by vaccination approximately match this optimum level. Furthermore, the observed stability of serum concentrations of vaccine-specific antibodies implies that the influxing plasmablasts mobilize a similar number of plasma cells and that competitive infectious challenges are not more frequent than once per month.