The Effect Of Individual Milk Proteins On Bioaccessibility Of Green Tea Flavan-3-Ols

While information regarding the impact of flavan-3-ol-protein interactions on food quality attributes (flavor, texture, and physical stability) exists, insight into the potential consequence of these interactions on bioavailability of health-promoting flavan-3-ols remains unclear. The ability of nonspecific protein interactions in flavan-3-ol rich foods and beverages to alter digestive stability and/or digestive release (bioaccessibility) of flavan-3-ols has been previously proposed but unconfirmed. The primary objective of this study was to characterize effects of individual milk proteins and the milk matrix on in vitro bioaccessibility of green tea flavan-3-ols from model beverage systems. As a secondary objective, the impact of protein gastrointestinal digestion on protein-flavan-3-ol binding was assessed using fluorometry. Protein solutions containing sodium-caseinate (S-CSN), α-lactalbumin (α-LA), β-lactoglobulin (β-LG) (0.356 mg/100 mL, 0.01 mg/100 mL, 0.035 mg/100 mL, respectively), or non-fat dry milk (NFDM, 0.1 mg/mL) were prepared in Jenness Koops buffer containing milk salts or dd water and formulated at dosages of 10, 20, and 40% (v/v) into model green tea beverages containing 60 mg/100 mL total flavan-3-ols. Samples were then subjected to in vitro digestion simulating human gastric and small intestinal conditions. Pre- and post-digestion flavan-3-ol profiles were assessed by HPLC and relative (%) and absolute (μmol/g) bioaccessibility of individual flavan-3-ols were calculated. With regards to green tea beverages formulated to 40% with milk protein solutions, inclusion of S-CSN significantly decreased (p0.05) were observed at protein and JK levels tested. SDS-PAGE results demonstrated only partial digestion of protein after peptic digestion, and degradation of proteins toEGCG, the main flavan-3-ol in green tea, occurs when protein is partially digested by pepsin in the gastric phase. Further digestion by pancreatin in the small intestinal phase appeared to reduce capacity for binding. Combined these data suggest that interactions between individual milk proteins and flavan-3-ols may alter bioaccessibility. However, the extent of these effects is subtle and dependent on the ability of individual interactions to survive normal digestive conditions. Interestingly, salts typically found in milk serum may exert protective effects on polyphenols from tea, stabilizing them to digestive reactions that may lead to their degradation

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2-specific memory T cell responses

Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2-specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2 specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with 700 mg bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation induced marker (AIM) assays in conjunction with intracellular cytokine staining (ICS). We demonstrate that most individuals with acute COVID-19 develop SARS-CoV-2-specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory was not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity

Influence of dietary polyphenols on carbohydrate intestinal digestion and absorption

Both epidemiological and clinical evidence support the notion that polyphenol rich foods and beverages may modify glycemic response, glucose homeostasis and subsequent risk of Type-2 diabetes. In vitro evidence typically derived from experiments with pure phenolics and phenolic rich extracts have pointed to this benefit being associated with two potential mechanisms: (1) the ability of specific polyphenolics to inhibit carbohydrate digestion (amylase and glucosidase) and (2) polyphenolic inhibition of intestinal glucose transport. While the high potential of these activities is evident, little is actually known regarding the extent to which these benefits are extendable to the actual food matrix these phenolics are naturally present in. Further, the extent to which co-consumption of polyphenol rich foods may actually result in decreased glycemic response from a mixed meal remains mostly unknown. Considering these limitations, additional insights are required in order to advance knowledge on the benefits of polyphenolics on glucomodulatory mechanisms and translation of these insights into meaningful recommendations and products for consumers. With this in mind, the objectives of these studies were to determine the extent to which phenolic-rich foods (grapes and potatoes) exert glucomodulatory properties in model food systems using in vitro and in vivo assessments. First, mechanisms associated with polyphenol rich extracts or model foods on carbohydrate intestinal digestion and glucose transport were investigated in vitro using a three-stage in vitro digestion model coupled to the Caco-2 human intestinal cell model. Components of this model used individually or in combination allowed for assessment of the two main mechanistic steps in phenolic modulation of glycemic response (starch digestion and glucose transport) in the context of interactions with bioaccessible phenolics. Additionally, the ability of the coupled in vitro digestion/Caco-2 model to predict in vivo outcomes was assessed. The first study compared the ability of 100% Niagara or Concord grape juice (GJ) phenolics to modify carbohydrase activity and intestinal glucose transport relative to a sugar sweetened beverage. While grape juices remain a major dietary source of phenolics, they are also well recognized to be naturally high in sugar content. Insights into the ability of natural fruit phenolics to modify glycemic response of grape juice were investigated in vitro. Also, in consideration that 100% GJ is consumed with meals, the extent to which modulation of carbohydrate digestion and intestinal absorption by GJ phenolics can be extended to a carbohydrate rich meal was evaluated. In the first experiment, inhibition of α-amylase and α-glucosidase by GJ extracts (300 and 500 μM total phenolics) and ability of GJ extracts (10 to 100 μM total phenolics) to modulate labelled glucose and fructose transport across Caco-2 intestinal cell monolayers compared to a phenolic-free control were determined. GJ extracts decreased α-glucosidase, but not α-amylase activity at both concentrations tested. Further, glucose and fructose transport were significantly (p<0.05) decreased in a dose-dependent manner by Niagara and Concord GJ extracts. In a second experiment, GJs and phenolic-free control beverages were co-digested in vitro with a starch-rich model meal. Resulting aqueous digesta (AQ) from both experiments were used to assess impact of bioaccessible GJ phenolics on carbohydrate digestion and glucose transport. Concord and Niagara GJs significantly decreased in vitro gastrointestinal digestion of carbohydrate from model meal compared with a sugar-matched control. Further, d7-glucose transport from AQ fraction of GJ and co-digested GJ and carbohydrate-rich meal across Caco-2 human intestinal cell monolayers was significantly decreased compared to phenolic-free sugar-sweetened control. The second study evaluated potential for phenolics from starch rich white, purple, or red potatoes to modulate carbohydrate digestion or glucose transport in a Caco-2 intestinal cell model. Potato phenolic extracts (300 μM) had no impact on α-amylase activity, and marginally decreased α-glucosidase activity. However, potato phenolic extracts (25-100μM) did decrease d7-glucose transport compared to phenolic-free control. Interestingly, whole potato phenolic extracts reduced glucose transport to a greater extent compared to those from potato peel. To determine if results from aforementioned in vitro assays are predictive of effects in vivo, a pilot clinical study (n=11) was completed to assess differences in acute blood glucose response and gastric emptying following consumption of phenolic-rich purple and red potato chips compared to white potato chips (50g available carbohydrate) containing lower level of total phenolics. Blood glucose levels were measured for up to two hours. Peak blood glucose levels were lower for pigmented chips, especially purple chips, compared to white chips without any significant changes in gastric emptying. These results suggest that potato phenolics may play a role in modulation of intestinal glucose transport and that these effects are translatable to consumer products such as potato chips. Taken together, these data support the notion that phenolics intrinsic to select foods have the ability to modify glycemic response through alteration of glucose transport and to a certain extent starch digestion. Therefore, it is likely that observed benefits associated with consumption of phenolic-rich foods and 100% fruit juices, as a part of an overall healthy diet, may be associated with the ability of intrinsic and bioaccessible phenolics to modify glycemic response. Future research that focuses on hypoglycemic effects of phenolic-rich foods should be larger scale and should evaluate a greater variety of phenolic-rich foods in order to better understand the extent to which phenolic class and food matrix impact hypoglycemic effects. Regarding meal-effects, a pilot clinical study should be completed to validate in vitro results and to provide information as to what degree various types of meal patterns alter glycemic effects of phenolic-rich foods. Such information can be leveraged in the development of phenolic-rich food products that have post-prandial glycemic effects and for making recommendations of dietary choices which may result in improved glucose homeostasis

Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model

While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%–11.5% inhibition; p &lt; 0.05). Separately, all GJ extracts (10–100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%–38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%–15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%–38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal

A gendered study of the working patterns of classical musicians: implications for practice

Despite an increase in participation at all levels of the music profession, women continue to experience less opportunities to forge careers in music and are less likely than men to apply for leadership positions. This paper presents results from a study in which 152 instrumental musicians reflected upon their professional practice and career aspirations. The study examined differences in the professional practice of male and female musicians, and found female musicians to be more likely to teach, and less likely to sustain performance positions due to the difficulties associated with managing family and other commitments whilst maintaining an uninterrupted career in music. It is proposed that educators have a crucial role to play in the development of curricula reflective of the realities of professional practice in a profession where interrupted careers can result in a loss of technical skills and outdated curricular and methodological knowledge

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2-specific memory T cell responses.

Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2-specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly and Company) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2-specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation-induced marker assays in conjunction with intracellular cytokine staining. We demonstrate that most individuals with acute COVID-19 developed SARS-CoV-2-specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory were not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity