Emergence of a New Norovirus GII.4 Variant and Changes in the Historical Biennial Pattern of Norovirus Outbreak Activity in Alberta,Canada, from 2008 to 2013

The public health impact of the emergence of new norovirus (NoV) strains is uncertain. A biennial pattern of alternating quiescent and epidemic levels of NoV outbreak activity associated with the emergence of new GII.4 variants was observed in Alberta, Canada, between July 2000 and June 2008. In this study, NoV genogroup I (GI) and GII strains isolated from 710 outbreak specimens in Alberta between July 2008 and January 2013 were characterized to update historical data. The seasonality and annual variation in NoV outbreak burden were analyzed over a 10-year period (July 2002 to June 2012). We found that GII.4-2006b had persisted as the predominant variant over three observation periods (July 2006 to June 2009) during which the biennial NoV outbreak pattern continued. The emergence of GII.4-2010 (winter 2009) was not associated with increased outbreak activity, and outbreak activity between July 2009 and June 2012 when GII.4-2010 predominated (67.5 to 97.7%) did not follow a biennial pattern. GII.4-2012 first emerged in Alberta in September 2011 and became predominant in observation period July 2012 to June 2013. NoV GI, relatively rare in past years, had a higher activity level (37.3%) as represented by GI.6 and GI.7 in the winter of 2012 to 2013. A higher proportion of GI outbreaks occurred in non-health care facility settings compared to GII. Our study suggests that factors other than new variants emergence contribute to the levels of NoV outbreak activity in Alberta.     

Children's risk and resilience following a natural disaster: Genetic vulnerability,posttraumatic stress,and depression

Objective

We examined children’s risk and resilience following a natural disaster, evaluating the role of stress, social support, and two genetic markers: the short allele of the serotonin transporter gene (5-HTTLPR), and the met allele of the Brain-Derived Neurotrophic Factor (BDNF).Under high levels of hurricane exposure or hurricane-related stressors, we expected children displaying the markers would report greater symptoms of posttraumatic stress disorder (PTSD) and depression than children without these markers. Social support was explored as an additional moderating variable.

Method

Eight months after Hurricane Ike, 116 children (M age=8.85 years, SD=.89; 54% girls) residing in Galveston, Texas, provided saliva samples and completed measures of hurricane exposure and stress, and symptoms of PTSD and depression; 80 also completed a social support measure.

Results

For BDNF, analyses revealed several Gene by Environment interactions; greater stress was related to more symptoms of PTSD and depression, and this effect was stronger for children with the met allele. No findings emerged for 5-HTTLPR. Stressors and social support also were associated with children’s PTSD and depressive symptoms.

Limitations

Findings should be tempered by the relatively small sample, especially for analysis that included social support.

Conclusions

The met allele (BDNF) may play a role in children’s disaster reactions. Further research should consider the complex interplay between genes, stressors, support, and psychological outcomes over time.     

Age-related changes in processing positive and negative feedback: Is there a positivity effect for older adults?

Older people sometimes show a bias toward the processing of positive information. In this study, we used an event-related potential approach to examine whether such a positivity bias is also present during feedback processing in older adults. Our results suggest that a fast initial monitoring process, as reflected in the feedback-related negativity (FRN), is sensitive to the expectancy of events irrespective of their valence for older (aged 70–77 years) as well as younger (aged 20–27 years) adults. In contrast, in a later evaluation process, associated with memory updating and indexed by the P300, both age groups preferably processed unexpected positive feedback. However, younger adults additionally differentiated between unexpected negative and expected feedback while older adults did not, probably due to a lower working memory capacity.     

PD1 expression and correlation with its ligands in oral cancer specimens and peripheral blood

ObjectivesThis study analyzed the expression of the PD1 receptor in tumor tissue and peripheral blood of oral squamous cell carcinoma (OSCC) patients, and correlated it with the PD1 ligands PD-L1 and PD-L2. The currently low response rates of checkpoint inhibitor treatment in OSCC could be increased by a better understanding of immune checkpoint biology. Despite evidence in the literature for upregulation of PD1 checkpoint ligands in OSCC tissue, there has been no correlation analysis of the PD1 receptor with its ligands in tissue specimens and peripheral blood of OSCC patients.Materials and methodsAn RT-qPCR analysis of PD1 mRNA expression was performed in oral cancer specimens, healthy mucosa, and corresponding blood samples. A cut-off point (COP) was determined and a chi-square (χ²) test was carried out. PD1 expression was correlated with previously reported PD-L1 and PD-L2 expression values using the Spearman test.ResultsTissue and blood specimens of 48 OSCC patients and 26 healthy individuals were analyzed. PD1 expression in OSCC specimens was significantly increased (p = 0.006) compared with healthy oral mucosa. PD1 overexpression in tissue samples showed a significant association with the presence of malignancy (p = 0.006). PD1 expression in tissue samples showed a significant positive correlation (p < 0.001) with the ligands PD-L1 and PD-L2. In contrast, there was no correlation between PD1 and its ligands in blood samples. However, there was a significant positive correlation (p < 0.001) between the ligands PD-L1 and PD-L2, both in tissue and blood samples.ConclusionsIncreased PD1 expression might be a manifestation of T-cell exhaustion in OSCC specimens, leading to immune tolerance. PD-L1/PD-L2-PD1 interaction may be a major mediator of local immunosuppression in OSCC, requiring advanced multimodal treatment protocols.     

Short-term benefit of smoking cessation in patients with coronary heart disease: estimates based on self-reported smoking data and serum cotinine measurements.

AIMS: To assess the short-term impact of smoking and smoking cessation measured by self-report and by serum cotinine on the risk of secondary cardiovascular disease events (CVD events). METHODS AND RESULTS: Cohort study among participants of an in-patient 3-week rehabilitation programme following an acute coronary syndrome or coronary artery revascularization. Smoking status at baseline was assessed by self-report (beginning of the rehabilitation programme, rehab) and serum cotinine (end of rehab). Active follow-up was conducted one year later. Subsequent CVD events were observed in 139 of the 967 patients. Both self-reported smoking status (odds ratio (OR) compared to continued smokers: recent quitters 0.96, former smokers 0.83, never smokers 0.54, p for trend 0.04) and serum cotinine (OR 0.59 (95% confidence interval (CI) 0.36-0.97) for cotinine-negative compared to cotinine-positive subjects) were associated with the occurrence of a secondary CVD event. After reclassification of all cotinine-positive subjects to continued smokers and cotinine-negative self-reported smokers to recent quitters, this association became even stronger. The OR now reached 0.71 (95% CI interval 0.38-1.33) for recent quitters, 0.64 (0.36-1.11) for former smokers and 0.44 (0.24-0.81) for never smokers (p-value for trend=0.009). CONCLUSION: The benefits of non-smoking and smoking cessation in cardiac patients are beyond controversy and might even be larger than suggested by previous studies which exclusively relied on self-reported smoking status.     

Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas

Background

There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non-small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC.

Methods

Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan–Meier method.

Results

Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages.

Conclusion

In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI.     

Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species- and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum (median [range] 50% inhibitory concentration [IC₅₀]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC₅₀s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P. vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.