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Dairy Beverages may be interesting from a nutritional, sensory and sustainable point of view. No-thermal technlogies, as the ultrasound stands out, where its application together with certain temperature levels, the so-called thermosonication, offers even more advantageous results. Orange whey drink (31% reconstituted whey and 69% v/v orange juice) was treated by high-temperature short-time treatment (HTST) and thermosonication (TS) at temperatures of 70, 80 and 90 °C (TS70, TS80 and TS90). Microbiological analysis (Lactic acid bacteria, molds and yeasts and total aerobic mesophilic bacteria count) and bioactive compounds (DPPH, ACE, α-glucosidase, α-amylase and ascorbic acid levels content) were perforned. For each microbial group, HTST showed the lowest log reductions (γ) in comparison to the TS formulations (p < 0.05). Moreover, the TS treatments performed with different maximum temperatures (from 70 to 90°C) did not affect the microbial inactivation (p > 0.05). TS samples are able to proportionate increased log reductions of aerobic mesophilic bactéria (AMB), yeasts and molds and lactic acid bacteria, in addition to providing greater stability in the microbial count during 21 days of storage when compared to HTST, which it achieves inadequate microbiological quality at 14 days. Among the TS treatments, there was no significant difference in the microbiological effect, indicating that the operation at the lowest temperature (70 °C) is sufficient to offer a safe product. Thermosonication also improved retention of bioactive compounds, being noted increased antioxidant activity and less ascorbic acid degradation compared to HTST treatment. TS80 and TS90 exhibited better results related to DPPH, ACE, α-glucosidase and α-amylase, and TS70 had the best performance related to ascorbic acid degradation (18%). Thermosonication proves to be a interesting alternative to orange juice-whey drink processing,
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