Hyaluronic acid-amphotericin B nanocomplexes: a promising anti-leishmanial drug delivery system.

The development of an effective amphotericin B (AmB) formulation to replace actual treatments available for leishmaniasis, which present serious drawbacks, is a challenge. Here we report the development of hyaluronic acid-amphotericin B self-assembled nanocomplexes (HA-AmB), processed by freeze-drying (FD) or nano spray-drying (SD), using a simple process that favors the non-covalent drug-polysaccharide association in an amorphous state. These water-soluble formulations, which presented a nanometric size (300-600 nm), high colloidal stability (zeta potential around -39 mV) and an AmB loading (15-18%) in aggregated and super aggregated states, demonstrated less in vitro cytotoxic and hemolytic effects compared to the free-drug. A significant decrease in the number of intramacrophagic L. infantum amastigotes upon treatment (IC50 of 0.026 and 0.030 µM for HA-AmB FD and HA-AmB SD, respectively) was also observed, and the best selectivity index (SI) was observed for the HA-AmB SD nanocomplex (SI of 651). Intravenous administration of the HA-AmB SD nanocomplex for 3 alternate days showed an effective parasite reduction in the spleen and liver of C57BL/6 mice without signs of toxicity commonly observed upon free-AmB treatment. Although lower than that achieved with AmBisome® in the liver, the observed parasite reduction for the nanocomplex was of a similar order of magnitude. The efficacy, stability, safety and low cost of the HA-AmB SD nanocomplex highlight its potential as an alternative treatment for leishmaniasis.

Preparedness in a public health emergency: determinants of willingness and readiness to respond in the onset of the COVID-19 pandemic.

OBJECTIVES: Healthcare professionals' high risk of infection and burnout in the first months of the COVID-19 pandemic probably hindered their much-needed preparedness to respond. We aimed to inform how individual and institutional factors contributed for the preparedness to respond during the first months of a public health emergency. STUDY DESIGN: Cross-sectional study. METHODS: We surveyed healthcare workers from a Local Health Unit in Portugal, which comprises primary health care centers and hospital services, including public health units and intensive care units, in the second and third months of the COVID-19 epidemic in Portugal. The 460 answers, completed by 252 participants (about 10% of the healthcare workers), were analyzed using descriptive statistics and multiple logistic regressions. We estimated adjusted odds ratios for the readiness and willingness to respond. RESULTS: Readiness to respond was associated with the perception of adequate infrastructures (aOR = 4.04, P < 0.005), lack of access to personal protective equipment (aOR = 0.26, P < 0.05) and organization (aOR = 0.31, P < 0.05). The willingness to act was associated with the perception of not being able to make a difference (aOR = 0.05, P < 0.005), risk of work-related burnout (aOR = 21.21, P < 0.01) and experiencing colleagues or patients' deaths due to COVID-19 (aOR = 0.24, P < 0.05). CONCLUSIONS: Adequate organization, infrastructures, and access to personal protective equipment may be crucial for workers' preparedness in a new public health emergency, as well workers' understanding of their roles and expected impact. These factors, together with the risk of work-related burnout, shall be taken into account in the planning of the response of healthcare institutions in future public health emergencies.

Depression symptoms as mediators of inequalities in self-reported health: the case of Southern European elderly.

Background: Inequalities in the distribution of self-reported health (SRH) have been widely reported. Its higher expressivity among women, elderly and least educated groups has been partly attributed to differences in their health perceptions. However, this subjectivity may be masking the burden of mental illness in these groups. Thus, we sought to understand if depression symptoms mediate inequalities in SRH. Methods: SHARE waves 4 and 6, pertaining to Spain, Italy and Portugal, were used (n2011 = 8517, n2015 = 11 046). Inequalities in SRH were calculated, comparing the risk amongst education level, gender and age groups, adjusting for chronic diseases, functional limitations and country fixed effects. We then tested depression symptoms as mediators. Results: Depression symptoms were associated with poor SRH (odds ratio (OR)2011 = 1.379, OR2015 = 1.384, P < 0.001). Their inclusion reduced the magnitude of the association between SRH and education, annulled the statistical significance for age, and reversed the gender effect. As expected, chronic diseases and functional limitations remained significant predictors of poor SRH. Conclusions: Depression symptoms, together with chronic diseases and functional limitations, explain the poorer SRH of the least educated, female and older groups in the Southern European population. Therefore, tackling inequalities in SRH must require focusing on mental health issues, which disproportionately affect the most vulnerable groups.