Leishmania infantum is an etiological agent of the life-threatening visceral form of leishmaniasis. Liposomal amphotericin B (AmB) followed by a short administration of miltefosine (MF) is a drug combination effective for treating visceral leishmaniasis in endemic regions of India. Resistance to MF can be due to point mutations in the miltefosine transporter (MT). Here we show that mutations in MT are also observed in Leishmania AmB-resistant mutants. The MF-induced MT mutations, but not the AmB induced mutations in MT, alter the translocation/uptake of MF. Moreover, mutations in the MT selected by AmB or MF have a major impact on lipid species that is linked to cross-resistance between both drugs. These alterations include changes of specific phospholipids, some of which are enriched with cyclopropanated fatty acids, as well as an increase in inositolphosphoceramide species. Collectively these results provide evidence of the risk of cross-resistance emergence derived from current AmB-MF sequential or co-treatments for visceral leishmaniasis.

Social support, not the mere presence of another individual, attenuated stress and pain during a CPT. Given the negative health consequences of stress and pain, clinical studies incorporating social support into medical procedures and treatments are warranted.

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We investigated the nature of covertly processed visual elements in a patient with simultanagnosia, a disorder characterized by the inability to perceive multiple aspects of a visual scene all at once. Using the first letter of the color words red, green, or blue, we created a novel testing paradigm that combined Navon global-local stimuli with a single-letter Stroop task. The letters R, G, or B were arranged in the overall configuration of a large R, G, or B. The patient never could report seeing the larger letter, and always could name the smaller letters. But, when asked to name ink color only, and ignore letter identity, the large letter covertly affected responding. That is, when the large letter was the same as the first letter of the ink color, the patient named ink color more quickly and accurately than when the large letter was incongruent with the correct response. Moreover, when the covert global and overt local visual processing conflicted, the global letter always dominated over the local letters, despite the patient's inability to perceive it consciously. These data show that the covert processing of global visual information in simultanagnosia can dominate overt local information, even across different streams of information processing.

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