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t formulations. By combining corona composition and uptake kinetics candidate corona proteins associated with reduced or increased uptake by cells can be identified and the liposome formulation can be tuned to obtain the desired uptake behavior. Corosolic acid (CA), a natural pentacyclic triterpenoid, exhibits antitumor and synergistic therapy effect with chemotherapeutic drugs mainly through inhibiting STAT3 activation. In this study, it is found that CA possesses cholesterol-like properties in liposome by regulating membrane phase behavior to form stable cholesterol-free CA liposomes (CALP). Compared with traditional cholesterol liposomes (CHOLP), CALP exhibit stronger membrane fusion and higher cellular uptake, and other functions including inhibition of STAT3 activation and suppression of the recruitment of macrophages to tumor microenvironment. Therefore, CALP is used as a functional carrier, and doxorubicin-loaded CALP (DOX/CALP) based on PEGylated liposomal doxorubicin (DOXILⓇ) are prepared by replacing its cholesterol with CA. The physicochemical properties and biological activities are compared with those of doxorubicin-loaded cholesterol liposomes (DOX/LP). Both DOX/CALP and DOX/LP possess approximately similar physical properties and exhibehavior. By replacing the cholesterol with CA, the liposomes were converted into high cellular uptake carriers, possessing anti-inflammatory activity and synergism with chemotherapeutic drugs. The variability of CALP formulations enabled to deliver therapeutic agents. The use of CALP to deliver doxorubicin not only significantly enhanced the therapeutic efficacy compared with the classic PEGylated liposomal doxorubicin, but also maintained the improved safety. Because CALP can be obtained by conventional liposome preparation methods, its use as functional drug carriers for solving low efficacy of present liposomal drugs would have promising application potential. BACKGROUND The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. This increase was accompanied by a shift in the predominant HIV subtype from B to CRF01_AE. Increasing evidence points to a difference in treatment responses between subtypes. We examined treatment failure and acquired drug resistance (ADR) in people living with HIV (PLHIVs) after one year on antiretrovirals (ARVs). METHODS PLHIV maintained on ARVs for one year were recruited. Treatment failure was defined as a viral load of ≥1000 copies/mL. Sanger sequencing for genotyping and drug resistance mutation (DRM) detection was performed on patients failing treatment. RESULTS 513 PLHIV were enrolled. The most common antiretroviral regimens were TDF+3TC+EFV (269) and AZT+3TC+EFV (155). 53 (10.3%) subjects failed treatment. Among these, 48 (90.6%) had DRMs, 84.9% were subtype CRF01_AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58 to 7.52 p less then 0.001). Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature. CONCLUSIONS HIV treatment failure at one year of treatment in the Philippines is 10.3%. We found unusually high tenofovir and multiclass resistance, and optimal ARV regimens may need to be reevaluated for CRF01_AE-predominant epidemics. We report for the first time in South America a HFMD case associated with Coxsackievirus A10. The viral strain belongs to a lineage involved in important European outbreaks and probably entered Uruguay after 2017 with a Greek origin. These findings call for strengthening the regional surveillance of HFMD. BACKGROUND The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil. METHODS Contacts of 1,672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated. RESULTS From a total of 1,180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (∼81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. Temsirolimus A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics. CONCLUSIONS Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care. Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https//drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. OBJECTIVE We describe epidemiological trends of human brucellosis in Germany over a 13 year period based on national surveillance data. METHODS We analyzed demographic, clinical, laboratory and exposure information of symptomatic laboratory-confirmed brucellosis cases notified 2006-18. Using official population data, we calculated incidences and risk ratios (RR). RESULTS From 2006-2018, 408 brucellosis cases were notified in Germany (mean annual incidence 0.38/1,000,000 population), of which 75% were travel-associated. Yearly notifications peaked in 2014 (n = 47) and remained elevated compared to 2006-2013 (mean n = 25). Asylum seekers (AS) arriving in Germany accounted for 9/44 (2015) and 15/36 (2016) cases, respectively. RR AS/non-AS 2015-2016 28, 95% CI 17-45. Unpasteurized milk products were most frequently notified as source of infection. Imported food and occupational exposure played a role in autochthonous cases. CONCLUSIONS The incidence of human brucellosis has markedly increased in recent years. Most of the observed rise in notifications can be explained by infections in AS.