Brilacidin, a novel antifungal agent against Cryptococcus neoformans.

Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

Edge magnetization and thermally induced spin current in nanostructured graphene.

In this work, the magnetic states and thermally induced spin currents in graphene nanoflake sizes with different sizes and shapes have been investigated using Hubbard model combined with non-equilibrium Green's function method. In addition to the antiferromagnetic (AFM) state governed by the sizes, shapes, armchair bond densities, and Coulomb energy, our calculations have also pointed out the emergence of ferromagnetic (FM) and complex magnetic states when the gate voltage is invoked in the graphene nanoflakes. More prominently, by exploiting the geometric symmetry of the nanoflakes without external fields, a pure spin current and zero charge current are generated in spin caloritronic device when the graphene nanoflakes are both in the AFM and FM states. The formation of pure spin currents driven by temperature difference depends on the graphene nanoflakes' size, shape, temperature and gate voltage as well. The study also shows the outstanding advantages of diamond-shaped graphene nanoflakes in both magnetic properties and spin currents. This result paves the way for the possibility of practical applications of graphene materials in spintronics and spin caloritronics.

Health services for reproductive tract infections among female migrant workers in industrial zones in Ha Noi, Viet Nam: an in-depth assessment.

BACKGROUND: Rural-to-urban migration involves a high proportion of females because job opportunities for female migrants have increased in urban industrial areas. Those who migrate may be healthier than those staying in the village and they may benefit from better health care services at destination, but the 'healthy' effect can be reversed at destination due to migration-related health risk factors. The study aimed to explore the need for health care services for reproductive tract infections (RTIs) among female migrants working in the Sai Dong industrial zone as well as their services utilization. METHODS: The cross sectional study employed a mixed method approach. A cohort of 300 female migrants was interviewed to collect quantitative data. Two focus groups and 20 in-depth interviews were conducted to collect qualitative data. We have used frequency and cross-tabulation techniques to analyze the quantitative data and the qualitative data was used to triangulate and to provide more in-depth information. RESULTS: The needs for health care services for RTI were high as 25% of participants had RTI syndromes. Only 21.6% of female migrants having RTI syndromes ever seek helps for health care services. Barriers preventing migrants to access services were traditional values, long working hours, lack of information, and high cost of services. Employers had limited interests in reproductive health of female migrants, and there was ineffective collaboration between the local health system and enterprises. These barriers were partly caused by lack of health promotion programs suitable for migrants. Most respondents needed more information on RTIs and preferred to receive these from their employers since they commonly work shifts--and spend most of their day time at work. CONCLUSION: While RTIs are a common health problem among female migrant workers in industrial zones, female migrants had many obstacles in accessing RTI care services. The findings from this study will help to design intervention models for RTI among this vulnerable group such as communication for behavioural impact of RTI health care, fostered collaboration between local health care services and employer enterprises, and on-site service (e.g. local or enterprise health clinics) strengthening.