Community acceptance and willingness-to-pay for a hypothetical Zika vaccine: A cross-sectional study in Indonesia

Background

Understanding people’s perceptions of the economic benefits of a potential Zika vaccine (ZV) is critical to accelerating its introduction into either public sector programs or private market. The aim of this study was to assess the acceptance and willingness-to-pay (WTP) for a hypothetical ZV and the associated explanatory variables in Indonesia.

Microvascular function in non‐dippers: Potential involvement of the salt sensitivity biomarker,marinobufagenin—The African‐PREDICT study

Suppressed nighttime blood pressure dipping is associated with salt sensitivity and may increase the hemodynamic load on the microvasculature. The mechanism remains unknown whereby salt sensitivity may increase the cardiovascular risk of non‐dippers. Marinobufagenin, a novel steroidal biomarker, is associated with salt sensitivity and other cardiovascular risk factors independent of blood pressure. The authors investigated whether microvascular function in non‐dippers is associated with marinobufagenin. The authors included 220 dippers and 154 non‐dippers (aged 20‐30 years) from the African‐PREDICT study, with complete 24‐hour urinary marinobufagenin and sodium data. The authors determined dipping status using 24‐hour blood pressure monitoring and defined nighttime non‐dipping <10%. The authors measured microvascular reactivity as retinal artery dilation in response to light flicker provocation. Young healthy non‐dippers and dippers presented with similar peak retinal artery dilation, urinary sodium, and MBG excretion (P > .05). However, only in non‐dippers did peak retinal artery dilation relate negatively to marinobufagenin excretion after single (r = ?0.20; P = .012), partial (r = ?0.23; P = .004), and multivariate‐adjusted regression analyses (Adj. R² = 0.34; β = ?0.26; P < .001). The authors also noted a relationship between peak artery dilation and estimated salt intake (Adj. R² = 0.30; β = ?0.14; P = .051), but it was lost upon inclusion of marinobufagenin (Adj. R² = 0.33; β = ?0.015; P = .86). No relationship between microvascular reactivity and marinobufagenin was evident in dippers (P = .77). Marinobufagenin, representing salt sensitivity, may be involved in early microvascular functional changes in young non‐dippers and thus contributes to the development of hypertension and cardiovascular disease later in life.     

Identification of a genetic subcluster of HIV type 1 subtype C (C') widespread in Ethiopia

Others and we have previously shown that subtype C is the predominant HIV-1 subtype and the major cause of AIDS in Ethiopia. The present study shows that subtype C in Ethiopia has a genetic subcluster, designated C', has not increased in frequency, or spread geographically, over the period 1988 (%C' = 23/53) to 1996-1997 (%C' = 26/50). There is no association of the HIV-1 subtype C or subcluster C' with geographic location, time of sample collection, or risk group in Ethiopia. Of 105 randomly collected samples representing 7 different towns in Ethiopia, all but 2 (1 subtype A from Addis Ababa, 1997 and 1 subtype D from Dessie, 1996) belong to subtype C.     

CXCR4 Inhibition with AMD3100 Sensitizes Prostate Cancer to Docetaxel Chemotherapy

Several in vitro and in vivo models have revealed the key role of CXCR4/CXCL12 axis in tumor-stroma interactions. Stromal cells present in the tumor microenvironment express high levels of CXCL12 protein, directly stimulating proliferation and migration of CXCR4-expressing cancer cells. This specific prosurvival influence of stromal cells on tumor cells is thought to protect them from cytotoxic chemotherapy and is postulated as a possible explanation for the minimal residual disease in hematological and solid cancers. Therefore, CXCR4/CXCL12 signaling is an attractive therapeutic target in cancer, as proven in preclinical leukemia mouse models, where CXCR4 inhibition sensitized cancer cells to conventional chemotherapy. This study investigates whether inhibition of CXCR4 with the specific inhibitor AMD3100 sensitizes human prostate cancer cells to docetaxel. We showed that both mouse and human stromal cell lines have a protective effect on PC3-luc cells by promoting their survival after chemotherapy. Furthermore, we demonstrated that AMD3100 sensitizes PC3-luc cells to docetaxel. In a subcutaneous xenograft mouse model of human prostate carcinoma, we showed that a combination of docetaxel and AMD3100 exerts increased antitumor effect compared with docetaxel alone. We concluded that CXCR4 inhibition chemosensitizes prostate cancer cells, both in vitro and in vivo. To explore the relevance of these findings, we analyzed CXCR4 expression levels in human prostate cancer samples. We found that cancer cells present in bone metastatic lesions express higher CXCR4 levels relative to the cells present in primary tumors and lymph node metastatic lesions. These findings underscore the potential of CXCR4 inhibitors as chemosensitizing agents.     

Multimorbidity,the Predominant Predictor of Quality-of-Life,Following Successful Spinal Cord Stimulation for Angina Pectoris

Background: Patients suffering from severe chronic angina pectoris (AP) that has become therapeutically refractory to medication and revascularization can be adequately treated with spinal cord stimulation (SCS). However, following SCS implantation for angina, not all patients show a consistent improvement in quality of life (QoL). Therefore, we sought to study the association of baseline characteristics and chronic multimorbidities on QoL following SCS implantation. Materials and Methods: All patients treated with SCS for refractory AP (rAP) were registered in a local data base. Patients who had discontinued SCS therapy were excluded from further analysis. Baseline characteristics, such as exercise limiting morbidities (chronic obstructive pulmonary disease [COPD], rheumatic disease, diabetes mellitus [DM], obesity expressed as body mass index [BMI] > 25) and demographic data, were retrieved from the data base. QoL was studied using the Seattle Angina Questionnaire and the RAND‐36 questionnaire. Results: During a 21‐year registration period (1986–2008), we enlisted 127 patients with SCS for rAP in our data base. Eighty‐two, of whom 59 died, had discontinued SCS and were lost to follow‐up. Out of the remaining 45 patients, 33 returned their questionnaires (73.3%). At SCS implantation, 72.7% of the patients were male, mean age 58 ± 8.5 years. Twenty‐four patients were in class III–IV angina and nine in class II‐III NYHA. After a follow‐up of 6.4 ± 4.1 years, men had better physical capacity and experienced less impairment in QoL resulting from physical or emotional restrictions (all p < 0.05) compared with women. Patients without COPD reported a better general health compared with those with rAP and COPD (p < 0.05). The association of DM on QoL was borderline significant. Patients with lower BMI scored better on emotional well‐being and perception of disease than those with a higher BMI (p < 0.05 and p < 0.05, respectively). None of the patients reported other morbidities limiting their exercise. Conclusions: Men showed a larger improvement in QoL following SCS implantation, compared with women. As SCS improves rAP, other chronic morbidities such as COPD, DM, and BMI may become the limiting factors for exercise and subsequently adversely affect QoL following implantation of an SCS system. As a consequence of the present relatively small single‐center study, we recommend studies regarding rAP and SCS to also address the effect of comorbidities on outcomes.