Summary
Background
Cryptococcal meningitis has fatality rates of 40%‐70%, resulting in 200 000 deaths each year. The best outcomes are achieved with amphotericin combined with flucytosine but ...flucytosine is expensive and unavailable where most disease occurs. More effective and affordable treatments are needed. Tamoxifen, a selective oestrogen receptor modulator frequently indicated for breast cancer, has been found to have synergistic activity against the Cryptococcus neoformans type strain when combined with amphotericin or fluconazole. It is cheap, off‐licence, widely available and well‐tolerated, and thus a pragmatic potential treatment for cryptococcal disease.
Objectives
We wanted to determine the susceptibility of clinical isolates of C. neoformans to tamoxifen alone and in combination with other antifungals, to determine whether there is sufficient evidence of activity to justify a clinical trial.
Methods
We used the CLSI broth microdilution protocol to test the susceptibility of 30 randomly selected clinical isolates of C. neoformans to tamoxifen, in dual combination with amphotericin, fluconazole or flucytosine, and in triple combination with amphotericin and fluconazole. Evidence of drug interactions was assessed using the fractional inhibitory concentration index.
Results
The MIC50 and MIC90 of tamoxifen were 4 and 16 mg/L, respectively. The combination of tamoxifen and amphotericin suggested a synergistic interaction in 20 of 30 (67%) isolates. There was no interaction between tamoxifen and either fluconazole or flucytosine. Synergy was maintained in 3‐Dimensional chequerboard testing. There was no evidence of antagonism.
Conclusions
Tamoxifen may be a useful addition to treatment with amphotericin and fluconazole for cryptococcal meningitis; a trial is justified.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background: Kangaroo mother care (KMC) is a low-cost intervention that is indicated to be a highly effective practice for which adoption and implementation are lacking. We investigated the current ...provision of KMC in Vietnam and explored differences among levels of healthcare facility. Methods: A survey form was sent to 187 hospitals in Vietnam, representing the three levels (central, provincial and district) of public hospital-based maternity services. Results: Overall response rate was 74% (138/187 hospitals). Routine KMC implementation was estimated in 49% of the hospitals. Where KMC was implemented or was being introduced, half of the hospitals had a written protocol and a KMC-dedicated room, and held educational courses on KMC. KMC was mainly performed by the mother. Skin-to-skin contact was mostly performed for <12 h/day (55%), exclusive breastfeeding at discharge was very frequent (89%) and early discharge was considered in half of the hospitals (54%), while follow-up was not performed in 29% of the hospitals. Participants considered follow-up after discharge as the main barrier to KMC implementation, and indicated education (of both parents and health caregivers) and environment upgrades (KMC-dedicated room and equipment) as the most important facilitators. Conclusions: Our survey estimated a limited implementation of KMC in Vietnamese maternity hospitals, with marked variations across the different levels of maternity services. Areas of improvements include increasing the duration of skin-to-skin contact, arranging dedicated spaces for KMC, involving the relatives (especially at district level), extending the availability of a written protocol, improving the eligibility process, and implementing early discharge and follow-up monitoring.
The fabrication of nonenzymatic glucose sensors is essential because of the enhancement in the selectivity and accuracy of these sensors. In this work, we used the electrodeposition approach to ...prepare a CeO2-based electrode for nonenzymatic glucose detection. A CeO2 branched-like nanostructure was successfully fabricated by electrodeposition on the surface of a Au substrate electrode at room temperature. The effects of cyclic voltammetry, CH3COOH content, and scan cycle number on the formation of the CeO2 branched-like nanostructure were investigated. The fabricated electrodes were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The results showed that a CeO2 branched-like nanostructure could be obtained with a CH3COOH content of 1.0 mL and a scan cycle number of 100 in a solution containing 0.015 M Ce(NO3)3, 0.01 M KCl, and 0.02 M CH3COONH4 and with a scan rate of 400 mV/s. The electrochemical characteristics of the sensor were examined by chronoamperometry and cyclic voltammetry. The results showed that the sensitivity of the sensor was 37.72 μA/mM·cm2 and the limit of detection (LOD) of the sensor was 0.093 mM. The findings in this work prove that it is feasible to fabricate CeO2-based sensors for nonenzymatic glucose detection.
The aim of the present study was to assess antimicrobial effects of naringenin (NRG), luteolin (LUT), myricetin (MCT), and protocatechuic acid (PCA) identified in a Hibiscus rosa sinensis flower ...against two reference strains and five clinical isolates of Helicobacter pylori. NRG displayed the most growth inhibitory and bactericidal activities to seven bacterial strains including six strains resistant to one or several antibiotics, azithromycin (MIC, 16–32 mg/L), erythromycin (MIC, 32 mg/L), levofloxacin (MIC, 32 mg/L), and/or metronidazole (24–64 mg/L), followed by LUT and MCT, while PCA showed weak activities toward the strains. These constituents had similar antibacterial activities toward the seven tested strains suggesting that these constituents and the antibiotics do not have a common mechanism of anti-H. pylori activity. NRG, LUT, and MCT resulted in a high percentage of coccoid forms of H. pylori. NRG exhibited the highest anti-biofilm formation activity. MCT produced the strongest inhibition of urease activity followed by LUT and PCA, whereas the activity of NRG was similar to standard inhibitor thiourea. The four constituents had no significant toxicity to human cell lines. A global attempt to decrease utilization of antibiotics justifies the need for further research on H. rosa sinensis derived materials containing NRG, LUT, MCT, and PCA as potential products or lead compounds for the prevention or treatment of diseases caused by H. pylori infection.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Non-platinum electrodes for photoelectric devices are challenging and attractive to the scientific community. A thin film of molybdenum disulfide (MoS2) was prepared on substrates coated with ...fluorine-doped tin oxide (FTO) to substitute the platinum counter electrode (CE) for dye-sensitized solar cells (DSSCs). Herein, we synthesized layered and honeycomb-like MoS2 thin films via the cyclic voltammetry (CV ) route. Thickness and morphology of the MoS2 thin films were controlled via the concentration of precursor solution. The obtained results showed that MoS2 thin films formed at a low precursor concentration had a layered morphology while a honeycomb-like MoS2 thin film was formed at a high precursor concentration. Both types of MoS2 thin film were composed of IT and 2H structures and exhibited excellent electrocatalytic activity for the I3-/I- redox couple. DSSCs assembled using these MoS2 CEs showed a maximal power conversion efficiency of 7.33%. The short-circuit value reached 16.3 mA-cm-2. which was higher than that of a conventional Pt/FTO CE (15.3 mA-cm-2). This work reports for the first time the possibility to obtain a honeycomb-like MoS2 thin film morphology by the CV method and investigates the effect of film structure on the electro-catalytic activity and photovoltaic performance of CEs for DSSC application.
Since Zika virus (ZIKV) was first detected in Uganda in 1947, serious outbreaks have occurred globally in Yap Island, French Polynesia and Brazil. Even though the number of infections and spread of ...ZIKV have risen sharply, the pathogenesis and replication mechanisms of ZIKV have not been well studied. ZIKV, a recently highlighted Flavivirus, is a mosquito-borne emerging virus causing microcephaly and the Guillain-Barre syndrome in fetuses and adults, respectively. ZIKV polyprotein consists of three structural proteins named C, prM and E and seven nonstructural proteins named NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 in an 11-kb single-stranded positive sense RNA genome. The function of individual ZIKV genes on the host innate immune response has barely been studied. In this study, we investigated the modulations of the NF-κB promoter activity induced by the MDA5/RIG-I signaling pathway. According to our results, two nonstructural proteins, NS2A and NS4A, dramatically suppressed the NF-κB promoter activity by inhibiting signaling factors involved in the MDA5/RIG-I signaling pathway. Interestingly, NS2A suppressed all components of MDA5/RIG-I signaling pathway, but NS4A inhibited most signaling molecules, except IKKε and IRF3-5D. In addition, both NS2A and NS4A downregulated MDA5-induced NF-κB promoter activity in a dosedependent manner. Taken together, our results suggest that NS2A and NS4A signifcantly antagonize MDA5/RIG-I-mediated NF-κB production, and these proteins seem to be controlled by different mechanisms. This study could help understand the mechanisms of how ZIKV controls innate immune responses and may also assist in the development of ZIKV-specific therapeutics.
Green bonds, a rapidly emerging financial instrument designed to bolster environmentally sustainable initiatives, are subject to the influence of the national culture on economic decisions. This ...study examines varying levels of green bond issuance and cultural dimensions based on Hofstede’s theory. Fixed-effects regression was employed to analyze a sample of 67 countries from 2008 to 2021. The results suggest that cultural dimensions such as individualism and long-term orientation promote green bond issuance, while masculinity restrains it. Additionally, this study examines the moderating effects of institutional quality and economic conditions. The findings show that the relationship between national culture and green bonds is more significant in countries with high institutional quality and lower income levels. While this study offers valuable insights for policymakers, investors, and issuers seeking to promote sustainable finance in different cultural contexts, it could be enhanced by providing more information on the methodology and data sources used, as well as by exploring the potential mechanisms underlying the observed relationships between cultural values and green bond issuance.
•A novel planar Hall sensor for low noise measurement of high magnetic field.•Quantify the pipe wall thickness reduction by the change of magnetic flux density.•Monitoring the wall thinning ...regardless its location in the pipe’s cross section.
Quantitatively monitoring the thickness reduction of a pipe by using magnetic flux density method remains a major challenge due to the small and gradual change in magnetic flux density over a long distance along a pipe. This signal change is hindered in the background signal of a detector that has a high temperature dependence and unstable background signal. In this paper, we verify the effectiveness of magnetic flux density method in quantitatively monitoring thickness reduction through simulation and experimental verification. Experimental results show that the proportion of magnetic signal change is 1.4 mT per 10% wall loss. To support this quantitative approach, we optimise an original ultra-high-sensitivity planar Hall sensor with high thermal stability and stable background signal versus time for measurement of the magnetic field over a wide range from 0 to 50 mT. The quantitative measurements were validated on test pipes with varying thickness steps of 0.5 mm.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ischemia is the reduction of blood flow to tissues by injury of blood vessels. Depending on the sites of tissues and grade of ischemia, ischemia can cause many serious complications. This study aimed ...to evaluate the effects of the E-twenty six (ETS) factor Ets variant 2 (ETV2) gene expression in angiogenesis and the effect of ETV2 gene therapy in a mouse model of hindlimb ischemia. The role of ETV2 on endothelial cell proliferation was evaluated in vitro. Knockdown of ETV2 expression was done using short hairpin RNA (shRNA) lentiviral viral particles. The ETV2 viral vector was injected into the skeletal muscles at the ligated and burned sites of the hindlimb and evaluated for its efficacy as a gene therapy modality for ischemia. Vascular regeneration in mice was indirectly evaluated by changes in mouse survival, necrotic grades of the leg, normal blood oxygen saturation level (SpO2), and blood flow by trypan blue injection assay. Preliminary data showed that ETV2 expression played a role in angiogenesis of endothelial cells. ETV2 overexpression could trigger and stimulate proliferation of skeletal endothelial cells. In vivo knockdown of ETV2 expression inhibited the auto-recovery of ischemic hindlimb, while overexpression of ETV2 helped to rescue leg loss and reduce necrosis, significantly improving angiogenesis in hindlimb ischemia. Our findings demonstrate that ETV2 gene therapy is a potentially effective modality for vascular regeneration.
A novel withanolide glucoside, plantagiolide I (1), a new withanolide glucoside, plantagiolide J (2), and six known compounds (3-8) were isolated from the whole plant of Tacca plantaginea. Their ...structures were determined by spectroscopic and chemical methods. Compound 3 significantly inhibited tumor necrosis factor alpha (TNFα)-induced nuclear factor-kappaB (NF-κB) transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values of 9.0 µM. Compounds 1-8 enhanced the transcriptional activity of peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner, with EC50 values ranging from 1.6 to 49.7 µM. In addition, the transactivational effects of compounds 1-8 on three individual PPAR subtypes, including PPARα, β(δ), and γ were evaluated. Compounds 1-8 significantly activated the transcriptional activity of PPARβ(δ), with EC50 values in a ranging from 4.1 to 29.6 µM. These results provide scientific support for the use of T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.
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